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FDA warns of increased risk of death with CLL, lymphoma drug
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
Pfizer plans a vaccine to target all coronaviruses
Ask the sibling of any celebrity and they’ll tell you they don’t get anywhere near the same attention. The same is true for coronaviruses – the one that causes COVID-19 has been in the spotlight for more than 2 years now, while the others at the moment circulate in relative obscurity.
With the knowledge that any of the other coronaviruses could pose a serious future threat, Pfizer and its partner BioNTech announced plans on June 29 to develop a vaccine that will work against SARS-CoV-2 (the virus that causes COVID-19) and the entire class, or family, of related coronaviruses.
Trials in people of this “pan-coronavirus” vaccine are scheduled to start this fall, Reuters reported.
“I applaud the sentiment that is long overdue,” said Eric Topol, MD, when asked to comment. “It is crucial that we get ahead of the virus, and the best way is to develop pan-betacoronavirus vaccines that are variant-proof.”
“We had potential to get them into clinical trials many months ago, but this is the first sign it may happen,” said Dr. Topol, executive vice president of Scripps Research and editor-in-chief for Medscape, WebMD’s sister site for health care professionals.
SARS-CoV-2 is not the first troublemaker in the coronavirus family. SARS, a coronavirus that causes acute respiratory syndrome, emerged in late 2002. A decade later, officials sounded the alarm about the coronavirus behind Middle East respiratory syndrome (MERS).
The coronavirus family is large, but only seven coronavirus types can infect humans, the CDC reports. Most cause mild to moderate upper respiratory tract infections, although some people can get pneumonia or bronchiolitis.
Unless you’re a virologist, immunologist, or public health official, you may be unaware that coronaviruses are one of the causes of the common cold, for example.
A version of this article first appeared on WebMD.com.
Ask the sibling of any celebrity and they’ll tell you they don’t get anywhere near the same attention. The same is true for coronaviruses – the one that causes COVID-19 has been in the spotlight for more than 2 years now, while the others at the moment circulate in relative obscurity.
With the knowledge that any of the other coronaviruses could pose a serious future threat, Pfizer and its partner BioNTech announced plans on June 29 to develop a vaccine that will work against SARS-CoV-2 (the virus that causes COVID-19) and the entire class, or family, of related coronaviruses.
Trials in people of this “pan-coronavirus” vaccine are scheduled to start this fall, Reuters reported.
“I applaud the sentiment that is long overdue,” said Eric Topol, MD, when asked to comment. “It is crucial that we get ahead of the virus, and the best way is to develop pan-betacoronavirus vaccines that are variant-proof.”
“We had potential to get them into clinical trials many months ago, but this is the first sign it may happen,” said Dr. Topol, executive vice president of Scripps Research and editor-in-chief for Medscape, WebMD’s sister site for health care professionals.
SARS-CoV-2 is not the first troublemaker in the coronavirus family. SARS, a coronavirus that causes acute respiratory syndrome, emerged in late 2002. A decade later, officials sounded the alarm about the coronavirus behind Middle East respiratory syndrome (MERS).
The coronavirus family is large, but only seven coronavirus types can infect humans, the CDC reports. Most cause mild to moderate upper respiratory tract infections, although some people can get pneumonia or bronchiolitis.
Unless you’re a virologist, immunologist, or public health official, you may be unaware that coronaviruses are one of the causes of the common cold, for example.
A version of this article first appeared on WebMD.com.
Ask the sibling of any celebrity and they’ll tell you they don’t get anywhere near the same attention. The same is true for coronaviruses – the one that causes COVID-19 has been in the spotlight for more than 2 years now, while the others at the moment circulate in relative obscurity.
With the knowledge that any of the other coronaviruses could pose a serious future threat, Pfizer and its partner BioNTech announced plans on June 29 to develop a vaccine that will work against SARS-CoV-2 (the virus that causes COVID-19) and the entire class, or family, of related coronaviruses.
Trials in people of this “pan-coronavirus” vaccine are scheduled to start this fall, Reuters reported.
“I applaud the sentiment that is long overdue,” said Eric Topol, MD, when asked to comment. “It is crucial that we get ahead of the virus, and the best way is to develop pan-betacoronavirus vaccines that are variant-proof.”
“We had potential to get them into clinical trials many months ago, but this is the first sign it may happen,” said Dr. Topol, executive vice president of Scripps Research and editor-in-chief for Medscape, WebMD’s sister site for health care professionals.
SARS-CoV-2 is not the first troublemaker in the coronavirus family. SARS, a coronavirus that causes acute respiratory syndrome, emerged in late 2002. A decade later, officials sounded the alarm about the coronavirus behind Middle East respiratory syndrome (MERS).
The coronavirus family is large, but only seven coronavirus types can infect humans, the CDC reports. Most cause mild to moderate upper respiratory tract infections, although some people can get pneumonia or bronchiolitis.
Unless you’re a virologist, immunologist, or public health official, you may be unaware that coronaviruses are one of the causes of the common cold, for example.
A version of this article first appeared on WebMD.com.
Commentary: Evaluating New Treatments and Cardiovascular Risk in PsA, July 2022
Inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by JAK inhibitors is efficacious in psoriatic arthritis (PsA). On the basis of the results of the pivotal SELECT-PsA 1 and SELECT-PsA 2 trials, upadacitinib, a selective JAK1 inhibitor, was recently approved for the treatment of PsA. However, data on longer-term disease control is still of interest. In a post hoc analysis of SELECT-PsA 1 and SELECT-PsA 2, Mease and colleagues assessed the proportion of patients achieving low disease activity or remission, as defined by validated measures such as the Disease Activity Index in Psoriatic Arthritis, Psoriatic Arthritis Disease Activity Scores, and minimal disease activity at 24 and 56 weeks. They showed that at week 24,a higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved low disease activityon the Disease Activity Index in Psoriatic Arthritis (range, 35%-48% vs 4%-16%; P< .05) and remission (range, 7%-11% vs 0%-3%; P< .05), with the responses sustained until week 56. Thus, upadacitinib provides sustained disease control in PsA and is an effective oral therapy.
Advanced targeted therapies have proven safety and efficacy over conventional therapies, often dramatically improving signs and symptoms. However, it is also desirable that such expensive therapies also show benefit in other outcomes, such as work productivity and quality of life. To evaluate work productivity and daily activity impairment and health-related quality of life in patients with inflammatory arthritis (rheumatoid arthritis, n=95;PsA,n=69, and axial spondyloarthritis, n=95) treated with golimumab, Dejaco and colleagues conducted a prospective, multicenter study in Austria. A total of 110 of these patients were followed for 24 months. At 24 months after golimumab initiation, there was significant improvement in total work productivity, presenteeism, activity impairment, and quality-of-life scores. Thus, golimumab, in addition to reducing disease activity, improved work productivity, activity, and health-related quality of life in patients with inflammatory arthritis, including PsA.
Cardiovascular disease (CVD) remains a major comorbidity in patients with PsA. This observation was once again confirmed in an observational, cross-sectional, case-control study including 207 patients with PsA and 414 matched controls from France. Degboe and colleagues demonstrated that patients with PsA had a higher prevalence of cardiovascular events and cardiovascular risk factors, such as high body mass index, triglyceride level, and hypertension, compared with controls. The proportion of patients with PsA who were estimated to have very high cardiovascular risk factors (≥10%) increased when SCORE (European Society of Cardiology Systematic Coronary Risk Evaluation) and QRISK2 (British Heart Foundation) equations considered the additional risk attributable to PsA. However, risk predictions scores such as SCORE and QRISK2 perform poorly in patients with PsA. To identify novel inflammatory and metabolic parameters associated with cardiovascular disease, Schwartz and colleagues looked at18F-fluorodeoxyglucose(FDG) PET-CT uptakeina cross-sectional analysis of a prospective study including 39 patients with biologic-treatment-naive PsA and 56 age-sex matched controls without PsA. They found that coronary artery disease (CAD) was significantly associated with visceral adiposity and FDG uptake in the bone marrow, liver, spleen, and subcutaneous adipose tissue. Thus, inflammatory and metabolic parameters, including visceral adiposity, potentially contribute to subclinical CAD in patients with PsA and may in the future be used to refine CVD risk and be targets for CAD preventive treatments.
Inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by JAK inhibitors is efficacious in psoriatic arthritis (PsA). On the basis of the results of the pivotal SELECT-PsA 1 and SELECT-PsA 2 trials, upadacitinib, a selective JAK1 inhibitor, was recently approved for the treatment of PsA. However, data on longer-term disease control is still of interest. In a post hoc analysis of SELECT-PsA 1 and SELECT-PsA 2, Mease and colleagues assessed the proportion of patients achieving low disease activity or remission, as defined by validated measures such as the Disease Activity Index in Psoriatic Arthritis, Psoriatic Arthritis Disease Activity Scores, and minimal disease activity at 24 and 56 weeks. They showed that at week 24,a higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved low disease activityon the Disease Activity Index in Psoriatic Arthritis (range, 35%-48% vs 4%-16%; P< .05) and remission (range, 7%-11% vs 0%-3%; P< .05), with the responses sustained until week 56. Thus, upadacitinib provides sustained disease control in PsA and is an effective oral therapy.
Advanced targeted therapies have proven safety and efficacy over conventional therapies, often dramatically improving signs and symptoms. However, it is also desirable that such expensive therapies also show benefit in other outcomes, such as work productivity and quality of life. To evaluate work productivity and daily activity impairment and health-related quality of life in patients with inflammatory arthritis (rheumatoid arthritis, n=95;PsA,n=69, and axial spondyloarthritis, n=95) treated with golimumab, Dejaco and colleagues conducted a prospective, multicenter study in Austria. A total of 110 of these patients were followed for 24 months. At 24 months after golimumab initiation, there was significant improvement in total work productivity, presenteeism, activity impairment, and quality-of-life scores. Thus, golimumab, in addition to reducing disease activity, improved work productivity, activity, and health-related quality of life in patients with inflammatory arthritis, including PsA.
Cardiovascular disease (CVD) remains a major comorbidity in patients with PsA. This observation was once again confirmed in an observational, cross-sectional, case-control study including 207 patients with PsA and 414 matched controls from France. Degboe and colleagues demonstrated that patients with PsA had a higher prevalence of cardiovascular events and cardiovascular risk factors, such as high body mass index, triglyceride level, and hypertension, compared with controls. The proportion of patients with PsA who were estimated to have very high cardiovascular risk factors (≥10%) increased when SCORE (European Society of Cardiology Systematic Coronary Risk Evaluation) and QRISK2 (British Heart Foundation) equations considered the additional risk attributable to PsA. However, risk predictions scores such as SCORE and QRISK2 perform poorly in patients with PsA. To identify novel inflammatory and metabolic parameters associated with cardiovascular disease, Schwartz and colleagues looked at18F-fluorodeoxyglucose(FDG) PET-CT uptakeina cross-sectional analysis of a prospective study including 39 patients with biologic-treatment-naive PsA and 56 age-sex matched controls without PsA. They found that coronary artery disease (CAD) was significantly associated with visceral adiposity and FDG uptake in the bone marrow, liver, spleen, and subcutaneous adipose tissue. Thus, inflammatory and metabolic parameters, including visceral adiposity, potentially contribute to subclinical CAD in patients with PsA and may in the future be used to refine CVD risk and be targets for CAD preventive treatments.
Inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by JAK inhibitors is efficacious in psoriatic arthritis (PsA). On the basis of the results of the pivotal SELECT-PsA 1 and SELECT-PsA 2 trials, upadacitinib, a selective JAK1 inhibitor, was recently approved for the treatment of PsA. However, data on longer-term disease control is still of interest. In a post hoc analysis of SELECT-PsA 1 and SELECT-PsA 2, Mease and colleagues assessed the proportion of patients achieving low disease activity or remission, as defined by validated measures such as the Disease Activity Index in Psoriatic Arthritis, Psoriatic Arthritis Disease Activity Scores, and minimal disease activity at 24 and 56 weeks. They showed that at week 24,a higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved low disease activityon the Disease Activity Index in Psoriatic Arthritis (range, 35%-48% vs 4%-16%; P< .05) and remission (range, 7%-11% vs 0%-3%; P< .05), with the responses sustained until week 56. Thus, upadacitinib provides sustained disease control in PsA and is an effective oral therapy.
Advanced targeted therapies have proven safety and efficacy over conventional therapies, often dramatically improving signs and symptoms. However, it is also desirable that such expensive therapies also show benefit in other outcomes, such as work productivity and quality of life. To evaluate work productivity and daily activity impairment and health-related quality of life in patients with inflammatory arthritis (rheumatoid arthritis, n=95;PsA,n=69, and axial spondyloarthritis, n=95) treated with golimumab, Dejaco and colleagues conducted a prospective, multicenter study in Austria. A total of 110 of these patients were followed for 24 months. At 24 months after golimumab initiation, there was significant improvement in total work productivity, presenteeism, activity impairment, and quality-of-life scores. Thus, golimumab, in addition to reducing disease activity, improved work productivity, activity, and health-related quality of life in patients with inflammatory arthritis, including PsA.
Cardiovascular disease (CVD) remains a major comorbidity in patients with PsA. This observation was once again confirmed in an observational, cross-sectional, case-control study including 207 patients with PsA and 414 matched controls from France. Degboe and colleagues demonstrated that patients with PsA had a higher prevalence of cardiovascular events and cardiovascular risk factors, such as high body mass index, triglyceride level, and hypertension, compared with controls. The proportion of patients with PsA who were estimated to have very high cardiovascular risk factors (≥10%) increased when SCORE (European Society of Cardiology Systematic Coronary Risk Evaluation) and QRISK2 (British Heart Foundation) equations considered the additional risk attributable to PsA. However, risk predictions scores such as SCORE and QRISK2 perform poorly in patients with PsA. To identify novel inflammatory and metabolic parameters associated with cardiovascular disease, Schwartz and colleagues looked at18F-fluorodeoxyglucose(FDG) PET-CT uptakeina cross-sectional analysis of a prospective study including 39 patients with biologic-treatment-naive PsA and 56 age-sex matched controls without PsA. They found that coronary artery disease (CAD) was significantly associated with visceral adiposity and FDG uptake in the bone marrow, liver, spleen, and subcutaneous adipose tissue. Thus, inflammatory and metabolic parameters, including visceral adiposity, potentially contribute to subclinical CAD in patients with PsA and may in the future be used to refine CVD risk and be targets for CAD preventive treatments.
Cannabis use causes spike in ED visits
Cannabis users had a 22% increased risk of an emergency department (ED) visit or hospitalization compared to nonusers, as determined from data from more than 30,000 individuals.
Although cannabis contains compounds similar to tobacco, “data published on the association between cannabis smoking and airways health have been contradictory,” and whether smoking cannabis increases a user’s risk of developing acute respiratory illness remains unclear, wrote Nicholas T. Vozoris, MD, of the University of Toronto, and colleagues.
In a study published in BMJ Open Respiratory Research, the investigators reviewed national health records data from 35,114 individuals aged 12-65 years for the period January 2009 to December 2015. Of these persons, 4,807 of the 6,425 who reported cannabis use in the past year were matched with 10,395 never-users who served as controls. The mean age of the study population at the index date was 35 years, and 42% were women; demographics were similar between users and control persons.
Overall, the odds of respiratory-related emergency department visits or hospitalizations were not significantly different between the cannabis users and the control persons (3.6% vs. 3.9%; odds ratio, 0.91). However, cannabis users had significantly greater odds of all-cause ED visits or hospitalizations (30.0% vs. 26.0%; OR, 1.22). All-cause mortality was 0.2% for both groups.
Respiratory problems were the second-highest reason for all-cause visits, the researchers noted. The lack of a difference in respiratory-related visits between cannabis users and nonusers conflicts somewhat with previous studies on this topic, which were limited, the researchers noted in their discussion.
The negative results also might stem from factors for which the researchers could not adjust, including insufficient cannabis smoke exposure among users in the study population, noninhalational cannabis use, which is less likely to have a respiratory effect, and possible secondhand exposure among control persons.
“It is also possible that our analysis might have been insufficiently powered to detect a significant signal with respect to the primary outcome,” they noted.
However, after the researchers controlled for multiple variables, the risk of an equally important morbidity outcome, all-cause ED visits or hospitalizations, was significantly greater among cannabis users than among control individuals, and respiratory reasons were the second most common cause for ED visits and hospitalizations in the all-cause outcome, they emphasized.
The study findings were limited by several factors, including the retrospective and observational design and the inability to control for all confounding variables, the researchers noted. Other limitations include the use of self-reports and potential for bias, the inability to perform dose-response analysis, and the high number of infrequent cannabis users in the study population.
However, the results suggest that cannabis use is associated with an increased risk of serious health events and should be discouraged, although more research is needed to confirm the current study findings, they concluded.
Consider range of causes for cannabis emergency visits
“With growing numbers of states legalizing recreational use of cannabis, it’s important to understand whether cannabis use is associated with increased emergency department visits,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, told this news organization.
Previous studies have shown an association between increased ED visits and cannabis use in states, especially with edibles, where cannabis is legal, and “the current study reinforces the elevated risk of ED visits along with hospitalizations,” he said.
“While the researchers found no increased risk of respiratory-related complaints among users compared to the general population, there was an associated increase in ED visits and hospitalizations, which is important to understand,” said Dr. Glatter, who was not involved in the study.
“While this observational study found that the incidence of respiratory complaints was not significantly different among frequent users of cannabis, the increased odds that cannabis users would require evaluation in the emergency room or even hospitalization was still apparent even after the investigators controlled for such factors as use of alcohol, tobacco, illicit drug use, or other mental health–related disorders,” Dr. Glatter noted.
“That said, it’s a bit surprising that with the continued popularity of vaping, especially among teens, there was still not any appreciable or significant increase in respiratory complaints observed. Beyond this finding, I was not surprised by the overall conclusions of the current study, as we continue to see an elevated number of patients presenting to the ED with adverse events related to cannabis use.”
Dr. Glatter noted that “the majority of patients we see in the ED are associated with use of edibles, since it takes longer for the person to feel the effects, leading the user to consume more of the product up front, with delayed effects lasting up to 12 hours. This is what gets people into trouble and leads to toxicity of cannabis, or ‘overdoses,’ “ he explained.
When consuming edible cannabis products, “[p]eople need to begin at low dosages and not take additional gummies up front, since it can take up to 2 or even 3 hours in some cases to feel the initial effects. With the drug’s effects lasting up to 12 hours, it’s especially important to avoid operating any motor vehicles, bicycles, or scooters, since reaction time is impaired, as well as overall judgment, balance, and fine motor skills,” Dr. Glatter said.
Cannabis can land users in the ED for a range of reasons, said Dr. Glatter. “According to the study, 15% of the emergency room visits and hospitalizations were due to acute trauma, 14% due to respiratory issues, and 13% to gastrointestinal illnesses. These effects were seen in first-time users but not those with chronic use, according to the study inclusion criteria.”
Cannabis use could result in physical injuries through “impaired judgment, coordination, combined with an altered state of consciousness or generalized drowsiness, that could contribute to an increase in motor vehicle collisions, along with an increased risk for falls leading to lacerations, fractures, contusions, or bruising,” said Dr. Glatter. “Cannabis may also lead to an altered sense of perception related to interactions with others, resulting in feelings of anxiety or restlessness culminating in physical altercations and other injuries.”
The current study indicates the need for understanding the potential physical and psychological effects of cannabis use, he said.
“Additional research is needed to better understand the relative percentage cases related to edibles vs. inhalation presenting to the ED,” he noted. “There is no question that edibles continue to present significant dangers for those who don’t read labels or remain poorly informed regarding their dosing as a result of delayed onset and longer duration,” he said. To help reduce risk of toxicity, the concept of a “high lasting 12-15 hours, as with edibles, as opposed to 3-4 hours from inhalation must be clearly stated on packaging and better communicated with users, as the toxicity with edibles is more often from lack of prior knowledge about onset of effects related to dosing.”
In addition, the “potential for psychosis to develop with more chronic cannabis use, along with cannabinoid hyperemesis syndrome should be on every clinician’s radar,” Dr. Glatter emphasized.
“The bottom line is that as more states legalize the use of cannabis, it’s vital to also implement comprehensive public education efforts to provide users with the reported risks associated with not only inhalation (vaping or flower) but also edibles, which account for an increasingly greater percentage of ED visits and associated adverse effects,” he said.
The study was supported by the Lung Association–Ontario, as well as by grants from the Ontario Ministry of Health and the Ministry of Long-Term Care. The researchers and Dr. Glatter have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cannabis users had a 22% increased risk of an emergency department (ED) visit or hospitalization compared to nonusers, as determined from data from more than 30,000 individuals.
Although cannabis contains compounds similar to tobacco, “data published on the association between cannabis smoking and airways health have been contradictory,” and whether smoking cannabis increases a user’s risk of developing acute respiratory illness remains unclear, wrote Nicholas T. Vozoris, MD, of the University of Toronto, and colleagues.
In a study published in BMJ Open Respiratory Research, the investigators reviewed national health records data from 35,114 individuals aged 12-65 years for the period January 2009 to December 2015. Of these persons, 4,807 of the 6,425 who reported cannabis use in the past year were matched with 10,395 never-users who served as controls. The mean age of the study population at the index date was 35 years, and 42% were women; demographics were similar between users and control persons.
Overall, the odds of respiratory-related emergency department visits or hospitalizations were not significantly different between the cannabis users and the control persons (3.6% vs. 3.9%; odds ratio, 0.91). However, cannabis users had significantly greater odds of all-cause ED visits or hospitalizations (30.0% vs. 26.0%; OR, 1.22). All-cause mortality was 0.2% for both groups.
Respiratory problems were the second-highest reason for all-cause visits, the researchers noted. The lack of a difference in respiratory-related visits between cannabis users and nonusers conflicts somewhat with previous studies on this topic, which were limited, the researchers noted in their discussion.
The negative results also might stem from factors for which the researchers could not adjust, including insufficient cannabis smoke exposure among users in the study population, noninhalational cannabis use, which is less likely to have a respiratory effect, and possible secondhand exposure among control persons.
“It is also possible that our analysis might have been insufficiently powered to detect a significant signal with respect to the primary outcome,” they noted.
However, after the researchers controlled for multiple variables, the risk of an equally important morbidity outcome, all-cause ED visits or hospitalizations, was significantly greater among cannabis users than among control individuals, and respiratory reasons were the second most common cause for ED visits and hospitalizations in the all-cause outcome, they emphasized.
The study findings were limited by several factors, including the retrospective and observational design and the inability to control for all confounding variables, the researchers noted. Other limitations include the use of self-reports and potential for bias, the inability to perform dose-response analysis, and the high number of infrequent cannabis users in the study population.
However, the results suggest that cannabis use is associated with an increased risk of serious health events and should be discouraged, although more research is needed to confirm the current study findings, they concluded.
Consider range of causes for cannabis emergency visits
“With growing numbers of states legalizing recreational use of cannabis, it’s important to understand whether cannabis use is associated with increased emergency department visits,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, told this news organization.
Previous studies have shown an association between increased ED visits and cannabis use in states, especially with edibles, where cannabis is legal, and “the current study reinforces the elevated risk of ED visits along with hospitalizations,” he said.
“While the researchers found no increased risk of respiratory-related complaints among users compared to the general population, there was an associated increase in ED visits and hospitalizations, which is important to understand,” said Dr. Glatter, who was not involved in the study.
“While this observational study found that the incidence of respiratory complaints was not significantly different among frequent users of cannabis, the increased odds that cannabis users would require evaluation in the emergency room or even hospitalization was still apparent even after the investigators controlled for such factors as use of alcohol, tobacco, illicit drug use, or other mental health–related disorders,” Dr. Glatter noted.
“That said, it’s a bit surprising that with the continued popularity of vaping, especially among teens, there was still not any appreciable or significant increase in respiratory complaints observed. Beyond this finding, I was not surprised by the overall conclusions of the current study, as we continue to see an elevated number of patients presenting to the ED with adverse events related to cannabis use.”
Dr. Glatter noted that “the majority of patients we see in the ED are associated with use of edibles, since it takes longer for the person to feel the effects, leading the user to consume more of the product up front, with delayed effects lasting up to 12 hours. This is what gets people into trouble and leads to toxicity of cannabis, or ‘overdoses,’ “ he explained.
When consuming edible cannabis products, “[p]eople need to begin at low dosages and not take additional gummies up front, since it can take up to 2 or even 3 hours in some cases to feel the initial effects. With the drug’s effects lasting up to 12 hours, it’s especially important to avoid operating any motor vehicles, bicycles, or scooters, since reaction time is impaired, as well as overall judgment, balance, and fine motor skills,” Dr. Glatter said.
Cannabis can land users in the ED for a range of reasons, said Dr. Glatter. “According to the study, 15% of the emergency room visits and hospitalizations were due to acute trauma, 14% due to respiratory issues, and 13% to gastrointestinal illnesses. These effects were seen in first-time users but not those with chronic use, according to the study inclusion criteria.”
Cannabis use could result in physical injuries through “impaired judgment, coordination, combined with an altered state of consciousness or generalized drowsiness, that could contribute to an increase in motor vehicle collisions, along with an increased risk for falls leading to lacerations, fractures, contusions, or bruising,” said Dr. Glatter. “Cannabis may also lead to an altered sense of perception related to interactions with others, resulting in feelings of anxiety or restlessness culminating in physical altercations and other injuries.”
The current study indicates the need for understanding the potential physical and psychological effects of cannabis use, he said.
“Additional research is needed to better understand the relative percentage cases related to edibles vs. inhalation presenting to the ED,” he noted. “There is no question that edibles continue to present significant dangers for those who don’t read labels or remain poorly informed regarding their dosing as a result of delayed onset and longer duration,” he said. To help reduce risk of toxicity, the concept of a “high lasting 12-15 hours, as with edibles, as opposed to 3-4 hours from inhalation must be clearly stated on packaging and better communicated with users, as the toxicity with edibles is more often from lack of prior knowledge about onset of effects related to dosing.”
In addition, the “potential for psychosis to develop with more chronic cannabis use, along with cannabinoid hyperemesis syndrome should be on every clinician’s radar,” Dr. Glatter emphasized.
“The bottom line is that as more states legalize the use of cannabis, it’s vital to also implement comprehensive public education efforts to provide users with the reported risks associated with not only inhalation (vaping or flower) but also edibles, which account for an increasingly greater percentage of ED visits and associated adverse effects,” he said.
The study was supported by the Lung Association–Ontario, as well as by grants from the Ontario Ministry of Health and the Ministry of Long-Term Care. The researchers and Dr. Glatter have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cannabis users had a 22% increased risk of an emergency department (ED) visit or hospitalization compared to nonusers, as determined from data from more than 30,000 individuals.
Although cannabis contains compounds similar to tobacco, “data published on the association between cannabis smoking and airways health have been contradictory,” and whether smoking cannabis increases a user’s risk of developing acute respiratory illness remains unclear, wrote Nicholas T. Vozoris, MD, of the University of Toronto, and colleagues.
In a study published in BMJ Open Respiratory Research, the investigators reviewed national health records data from 35,114 individuals aged 12-65 years for the period January 2009 to December 2015. Of these persons, 4,807 of the 6,425 who reported cannabis use in the past year were matched with 10,395 never-users who served as controls. The mean age of the study population at the index date was 35 years, and 42% were women; demographics were similar between users and control persons.
Overall, the odds of respiratory-related emergency department visits or hospitalizations were not significantly different between the cannabis users and the control persons (3.6% vs. 3.9%; odds ratio, 0.91). However, cannabis users had significantly greater odds of all-cause ED visits or hospitalizations (30.0% vs. 26.0%; OR, 1.22). All-cause mortality was 0.2% for both groups.
Respiratory problems were the second-highest reason for all-cause visits, the researchers noted. The lack of a difference in respiratory-related visits between cannabis users and nonusers conflicts somewhat with previous studies on this topic, which were limited, the researchers noted in their discussion.
The negative results also might stem from factors for which the researchers could not adjust, including insufficient cannabis smoke exposure among users in the study population, noninhalational cannabis use, which is less likely to have a respiratory effect, and possible secondhand exposure among control persons.
“It is also possible that our analysis might have been insufficiently powered to detect a significant signal with respect to the primary outcome,” they noted.
However, after the researchers controlled for multiple variables, the risk of an equally important morbidity outcome, all-cause ED visits or hospitalizations, was significantly greater among cannabis users than among control individuals, and respiratory reasons were the second most common cause for ED visits and hospitalizations in the all-cause outcome, they emphasized.
The study findings were limited by several factors, including the retrospective and observational design and the inability to control for all confounding variables, the researchers noted. Other limitations include the use of self-reports and potential for bias, the inability to perform dose-response analysis, and the high number of infrequent cannabis users in the study population.
However, the results suggest that cannabis use is associated with an increased risk of serious health events and should be discouraged, although more research is needed to confirm the current study findings, they concluded.
Consider range of causes for cannabis emergency visits
“With growing numbers of states legalizing recreational use of cannabis, it’s important to understand whether cannabis use is associated with increased emergency department visits,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, told this news organization.
Previous studies have shown an association between increased ED visits and cannabis use in states, especially with edibles, where cannabis is legal, and “the current study reinforces the elevated risk of ED visits along with hospitalizations,” he said.
“While the researchers found no increased risk of respiratory-related complaints among users compared to the general population, there was an associated increase in ED visits and hospitalizations, which is important to understand,” said Dr. Glatter, who was not involved in the study.
“While this observational study found that the incidence of respiratory complaints was not significantly different among frequent users of cannabis, the increased odds that cannabis users would require evaluation in the emergency room or even hospitalization was still apparent even after the investigators controlled for such factors as use of alcohol, tobacco, illicit drug use, or other mental health–related disorders,” Dr. Glatter noted.
“That said, it’s a bit surprising that with the continued popularity of vaping, especially among teens, there was still not any appreciable or significant increase in respiratory complaints observed. Beyond this finding, I was not surprised by the overall conclusions of the current study, as we continue to see an elevated number of patients presenting to the ED with adverse events related to cannabis use.”
Dr. Glatter noted that “the majority of patients we see in the ED are associated with use of edibles, since it takes longer for the person to feel the effects, leading the user to consume more of the product up front, with delayed effects lasting up to 12 hours. This is what gets people into trouble and leads to toxicity of cannabis, or ‘overdoses,’ “ he explained.
When consuming edible cannabis products, “[p]eople need to begin at low dosages and not take additional gummies up front, since it can take up to 2 or even 3 hours in some cases to feel the initial effects. With the drug’s effects lasting up to 12 hours, it’s especially important to avoid operating any motor vehicles, bicycles, or scooters, since reaction time is impaired, as well as overall judgment, balance, and fine motor skills,” Dr. Glatter said.
Cannabis can land users in the ED for a range of reasons, said Dr. Glatter. “According to the study, 15% of the emergency room visits and hospitalizations were due to acute trauma, 14% due to respiratory issues, and 13% to gastrointestinal illnesses. These effects were seen in first-time users but not those with chronic use, according to the study inclusion criteria.”
Cannabis use could result in physical injuries through “impaired judgment, coordination, combined with an altered state of consciousness or generalized drowsiness, that could contribute to an increase in motor vehicle collisions, along with an increased risk for falls leading to lacerations, fractures, contusions, or bruising,” said Dr. Glatter. “Cannabis may also lead to an altered sense of perception related to interactions with others, resulting in feelings of anxiety or restlessness culminating in physical altercations and other injuries.”
The current study indicates the need for understanding the potential physical and psychological effects of cannabis use, he said.
“Additional research is needed to better understand the relative percentage cases related to edibles vs. inhalation presenting to the ED,” he noted. “There is no question that edibles continue to present significant dangers for those who don’t read labels or remain poorly informed regarding their dosing as a result of delayed onset and longer duration,” he said. To help reduce risk of toxicity, the concept of a “high lasting 12-15 hours, as with edibles, as opposed to 3-4 hours from inhalation must be clearly stated on packaging and better communicated with users, as the toxicity with edibles is more often from lack of prior knowledge about onset of effects related to dosing.”
In addition, the “potential for psychosis to develop with more chronic cannabis use, along with cannabinoid hyperemesis syndrome should be on every clinician’s radar,” Dr. Glatter emphasized.
“The bottom line is that as more states legalize the use of cannabis, it’s vital to also implement comprehensive public education efforts to provide users with the reported risks associated with not only inhalation (vaping or flower) but also edibles, which account for an increasingly greater percentage of ED visits and associated adverse effects,” he said.
The study was supported by the Lung Association–Ontario, as well as by grants from the Ontario Ministry of Health and the Ministry of Long-Term Care. The researchers and Dr. Glatter have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Primary care providers miss out on payments for prevention, coordination
According to the new research, primary care physicians used these codes for a median of only 2.3% of services provided to eligible patients.
“Investing in primary care is good for the health of patients, for achieving health equity, and for improving the value of health care spending, and yet the U.S. underinvests in primary care,” lead author Sumit D. Agarwal, MD, of Brigham and Women’s Hospital, Boston, said in an interview.
“One strategy to rectify this has been to add billing codes to the physician fee schedule for PCPs to use and thus raise primary care spending; Medicare has been activating new codes for the better part of 2 decades, and we wanted to investigate how successful this strategy of adding codes to the Medicare Physician Fee Schedule (MPFS) schedule has been to inform discussions on how best to finance primary care in the United States,” he said.
In a study published in Annals of Internal Medicine, Dr. Agarwal and colleagues reviewed nationally representative claims and survey data from 2019 and 2020. They analyzed 34 distinct prevention and coordination codes in 13 categories that have been added the MPFS since 2005. Of these, four involved coordination of care (cognitive impairment, behavioral health integration, chronic care management, and transitional care management). The other nine categories in prevention were wellness visits, advance care planning, shared decision making for lung cancer screening, obesity counseling, behavioral counseling for CVD, depression screening, alcohol misuse counseling, alcohol misuse screening, and smoking cessation counseling.
Overall, 8.8%-100% of older adult patients were eligible for preventive services. A range of patients (5.0%-60.6%) had codes for receiving services in their patient information.
“However, a much smaller fraction of eligible patients was billed for having received the service, ranging from less than 1% for alcohol misuse counseling or obesity counseling to 35.8% for wellness visits, with most below 10%,” the researchers wrote.
The median use of billing codes was 2.3% for eligible patients.
A PCP who provided and billed preventive services to half of all eligible patients could potentially increase revenues of $1,269 to $45,406 per code, with an annual revenue increase of $124,435 (interquartile range $30,654 to $226,813) for prevention services. Similarly, providing and billing coordination of care service to half of all eligible patients could increase revenue by $86,082 (IQR, $18,011 to $154,152).
“Importantly, all of these prevention and coordination codes involve decomposing the comprehensive care of a patient into component parts, each with multiple steps and checklists, which may be inconsistent with how PCPs practice and document care,” the researchers wrote in their discussion. “Unlike hospitals, primary care practices are typically unable to use departments of trained coders to maximize billing and ensure that documentation matches the requirements specified in billing rules,” they added.
The study findings were limited by several factors including the focus only on the Medicare segment of PCPs’ panels, which suggests conservative estimates of reimbursement, the researchers noted. Other limitations include response bias to the use of surveys, lack of survey data on specific billing requirements, and the potential underestimation of services by PCPs who delivered some, but not all, components of a service code.
However, the results reflect previous research to show the underutilization of prevention and coordination codes in primary care, and the need for ways to increase their use, the researchers said. “The discrepancies between service eligibility, provision of services regardless of billing, and actual billing suggest that attempting to codify each distinct activity done by a PCP in the MPFS may not be an effective strategy for supporting primary care,” they concluded.
Barriers to code use persist for PCPs
“What surprised us was that there were many codes; we analyzed 34 in the paper in 13 distinct categories of services, and Medicare continues to add new primary care codes to the fee schedule,” Dr. Agarwal said in an interview. Also surprising, “take-up is low virtually across the board, and this isn’t for lack of eligibility,” he said. The low use of the codes “is not for lack of counseling patients on diet, drinking, exercise, smoking, or anything else for which these codes are meant to pay PCPs ... The potential revenue from these codes in aggregate is huge,” Dr. Agarwal emphasized.
“My hope is not necessarily that physicians read this study and start using some or all of these codes more frequently,” said Dr. Agarwal. “It can be tempting to think of this as money left on the table, but it’s not; there are compliance, billing, and opportunity costs from using these codes,” he said. “For individual PCPs seeing individual patients for the breadth that is primary care, I’m not sure the juice is worth the squeeze,” he added. “My coauthors and I are all primary care physicians. We know from our research and first-hand that these codes can be cumbersome to use.” These codes also don’t reflect how PCPs practice, he said. “PCPs are not in the business of slicing and dicing a visit or patient to extract as much revenue as possible. The physician-patient interaction is more complex, and richer, than these codes imply. Instead, I hope our paper encourages Medicare and policymakers to take a harder look at other strategies for investing in primary care,” Dr. Agarwal added.
As for additional research, “Primary care spending is going in the wrong direction,” said Dr. Agarwal. “We need to figure out how best to finance primary care in the United States.”
Recent studies have examined the successes and limitations of the primary care medical home model, Medicare’s Comprehensive Primary Care Initiative, and primary care spending legislation, he said. “Our study is another piece of the puzzle: at least in its current form,” and the results suggest “that one-off codes were nice in theory but not in practice,” he noted.
New codes are cumbersome
“It’s tempting to interpret underuse of new billing codes as a simple change management problem,” Davoren Chick, MD, chief learning officer of the American College of Physicians, wrote in an accompanying editorial. However, the underuse of codes for preventive service and coordination of care likely stems from the details of the codes, he said.
The new codes require the documentation of specific components and a minimum duration of services, he explained. “Codes that reward discrete service episodes disadvantage physicians who appropriately integrate preventive services within a continuous patient care relationship,” he added.
Dr. Chick presented an example of a primary care physician who would have to deliver intensive behavioral therapy for obesity in 15-minute episodes outside of a routine office visit to meet the billing criteria for current Medicare codes.
Dr. Chick called on clinicians to educate themselves on the coding rules for the services they provide “not only to optimize current payment but also to advocate for change.”
He concluded: “Widespread underuse of new preventive service and coordination of care codes reflects system failure, not physician failure. We must stand firm with this knowledge to demand increased payment for feasible, patient-centered primary care commensurate with its value in achieving better outcomes and lower costs.”
The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Agarwal and Dr. Chick had no financial conflicts to disclose.
According to the new research, primary care physicians used these codes for a median of only 2.3% of services provided to eligible patients.
“Investing in primary care is good for the health of patients, for achieving health equity, and for improving the value of health care spending, and yet the U.S. underinvests in primary care,” lead author Sumit D. Agarwal, MD, of Brigham and Women’s Hospital, Boston, said in an interview.
“One strategy to rectify this has been to add billing codes to the physician fee schedule for PCPs to use and thus raise primary care spending; Medicare has been activating new codes for the better part of 2 decades, and we wanted to investigate how successful this strategy of adding codes to the Medicare Physician Fee Schedule (MPFS) schedule has been to inform discussions on how best to finance primary care in the United States,” he said.
In a study published in Annals of Internal Medicine, Dr. Agarwal and colleagues reviewed nationally representative claims and survey data from 2019 and 2020. They analyzed 34 distinct prevention and coordination codes in 13 categories that have been added the MPFS since 2005. Of these, four involved coordination of care (cognitive impairment, behavioral health integration, chronic care management, and transitional care management). The other nine categories in prevention were wellness visits, advance care planning, shared decision making for lung cancer screening, obesity counseling, behavioral counseling for CVD, depression screening, alcohol misuse counseling, alcohol misuse screening, and smoking cessation counseling.
Overall, 8.8%-100% of older adult patients were eligible for preventive services. A range of patients (5.0%-60.6%) had codes for receiving services in their patient information.
“However, a much smaller fraction of eligible patients was billed for having received the service, ranging from less than 1% for alcohol misuse counseling or obesity counseling to 35.8% for wellness visits, with most below 10%,” the researchers wrote.
The median use of billing codes was 2.3% for eligible patients.
A PCP who provided and billed preventive services to half of all eligible patients could potentially increase revenues of $1,269 to $45,406 per code, with an annual revenue increase of $124,435 (interquartile range $30,654 to $226,813) for prevention services. Similarly, providing and billing coordination of care service to half of all eligible patients could increase revenue by $86,082 (IQR, $18,011 to $154,152).
“Importantly, all of these prevention and coordination codes involve decomposing the comprehensive care of a patient into component parts, each with multiple steps and checklists, which may be inconsistent with how PCPs practice and document care,” the researchers wrote in their discussion. “Unlike hospitals, primary care practices are typically unable to use departments of trained coders to maximize billing and ensure that documentation matches the requirements specified in billing rules,” they added.
The study findings were limited by several factors including the focus only on the Medicare segment of PCPs’ panels, which suggests conservative estimates of reimbursement, the researchers noted. Other limitations include response bias to the use of surveys, lack of survey data on specific billing requirements, and the potential underestimation of services by PCPs who delivered some, but not all, components of a service code.
However, the results reflect previous research to show the underutilization of prevention and coordination codes in primary care, and the need for ways to increase their use, the researchers said. “The discrepancies between service eligibility, provision of services regardless of billing, and actual billing suggest that attempting to codify each distinct activity done by a PCP in the MPFS may not be an effective strategy for supporting primary care,” they concluded.
Barriers to code use persist for PCPs
“What surprised us was that there were many codes; we analyzed 34 in the paper in 13 distinct categories of services, and Medicare continues to add new primary care codes to the fee schedule,” Dr. Agarwal said in an interview. Also surprising, “take-up is low virtually across the board, and this isn’t for lack of eligibility,” he said. The low use of the codes “is not for lack of counseling patients on diet, drinking, exercise, smoking, or anything else for which these codes are meant to pay PCPs ... The potential revenue from these codes in aggregate is huge,” Dr. Agarwal emphasized.
“My hope is not necessarily that physicians read this study and start using some or all of these codes more frequently,” said Dr. Agarwal. “It can be tempting to think of this as money left on the table, but it’s not; there are compliance, billing, and opportunity costs from using these codes,” he said. “For individual PCPs seeing individual patients for the breadth that is primary care, I’m not sure the juice is worth the squeeze,” he added. “My coauthors and I are all primary care physicians. We know from our research and first-hand that these codes can be cumbersome to use.” These codes also don’t reflect how PCPs practice, he said. “PCPs are not in the business of slicing and dicing a visit or patient to extract as much revenue as possible. The physician-patient interaction is more complex, and richer, than these codes imply. Instead, I hope our paper encourages Medicare and policymakers to take a harder look at other strategies for investing in primary care,” Dr. Agarwal added.
As for additional research, “Primary care spending is going in the wrong direction,” said Dr. Agarwal. “We need to figure out how best to finance primary care in the United States.”
Recent studies have examined the successes and limitations of the primary care medical home model, Medicare’s Comprehensive Primary Care Initiative, and primary care spending legislation, he said. “Our study is another piece of the puzzle: at least in its current form,” and the results suggest “that one-off codes were nice in theory but not in practice,” he noted.
New codes are cumbersome
“It’s tempting to interpret underuse of new billing codes as a simple change management problem,” Davoren Chick, MD, chief learning officer of the American College of Physicians, wrote in an accompanying editorial. However, the underuse of codes for preventive service and coordination of care likely stems from the details of the codes, he said.
The new codes require the documentation of specific components and a minimum duration of services, he explained. “Codes that reward discrete service episodes disadvantage physicians who appropriately integrate preventive services within a continuous patient care relationship,” he added.
Dr. Chick presented an example of a primary care physician who would have to deliver intensive behavioral therapy for obesity in 15-minute episodes outside of a routine office visit to meet the billing criteria for current Medicare codes.
Dr. Chick called on clinicians to educate themselves on the coding rules for the services they provide “not only to optimize current payment but also to advocate for change.”
He concluded: “Widespread underuse of new preventive service and coordination of care codes reflects system failure, not physician failure. We must stand firm with this knowledge to demand increased payment for feasible, patient-centered primary care commensurate with its value in achieving better outcomes and lower costs.”
The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Agarwal and Dr. Chick had no financial conflicts to disclose.
According to the new research, primary care physicians used these codes for a median of only 2.3% of services provided to eligible patients.
“Investing in primary care is good for the health of patients, for achieving health equity, and for improving the value of health care spending, and yet the U.S. underinvests in primary care,” lead author Sumit D. Agarwal, MD, of Brigham and Women’s Hospital, Boston, said in an interview.
“One strategy to rectify this has been to add billing codes to the physician fee schedule for PCPs to use and thus raise primary care spending; Medicare has been activating new codes for the better part of 2 decades, and we wanted to investigate how successful this strategy of adding codes to the Medicare Physician Fee Schedule (MPFS) schedule has been to inform discussions on how best to finance primary care in the United States,” he said.
In a study published in Annals of Internal Medicine, Dr. Agarwal and colleagues reviewed nationally representative claims and survey data from 2019 and 2020. They analyzed 34 distinct prevention and coordination codes in 13 categories that have been added the MPFS since 2005. Of these, four involved coordination of care (cognitive impairment, behavioral health integration, chronic care management, and transitional care management). The other nine categories in prevention were wellness visits, advance care planning, shared decision making for lung cancer screening, obesity counseling, behavioral counseling for CVD, depression screening, alcohol misuse counseling, alcohol misuse screening, and smoking cessation counseling.
Overall, 8.8%-100% of older adult patients were eligible for preventive services. A range of patients (5.0%-60.6%) had codes for receiving services in their patient information.
“However, a much smaller fraction of eligible patients was billed for having received the service, ranging from less than 1% for alcohol misuse counseling or obesity counseling to 35.8% for wellness visits, with most below 10%,” the researchers wrote.
The median use of billing codes was 2.3% for eligible patients.
A PCP who provided and billed preventive services to half of all eligible patients could potentially increase revenues of $1,269 to $45,406 per code, with an annual revenue increase of $124,435 (interquartile range $30,654 to $226,813) for prevention services. Similarly, providing and billing coordination of care service to half of all eligible patients could increase revenue by $86,082 (IQR, $18,011 to $154,152).
“Importantly, all of these prevention and coordination codes involve decomposing the comprehensive care of a patient into component parts, each with multiple steps and checklists, which may be inconsistent with how PCPs practice and document care,” the researchers wrote in their discussion. “Unlike hospitals, primary care practices are typically unable to use departments of trained coders to maximize billing and ensure that documentation matches the requirements specified in billing rules,” they added.
The study findings were limited by several factors including the focus only on the Medicare segment of PCPs’ panels, which suggests conservative estimates of reimbursement, the researchers noted. Other limitations include response bias to the use of surveys, lack of survey data on specific billing requirements, and the potential underestimation of services by PCPs who delivered some, but not all, components of a service code.
However, the results reflect previous research to show the underutilization of prevention and coordination codes in primary care, and the need for ways to increase their use, the researchers said. “The discrepancies between service eligibility, provision of services regardless of billing, and actual billing suggest that attempting to codify each distinct activity done by a PCP in the MPFS may not be an effective strategy for supporting primary care,” they concluded.
Barriers to code use persist for PCPs
“What surprised us was that there were many codes; we analyzed 34 in the paper in 13 distinct categories of services, and Medicare continues to add new primary care codes to the fee schedule,” Dr. Agarwal said in an interview. Also surprising, “take-up is low virtually across the board, and this isn’t for lack of eligibility,” he said. The low use of the codes “is not for lack of counseling patients on diet, drinking, exercise, smoking, or anything else for which these codes are meant to pay PCPs ... The potential revenue from these codes in aggregate is huge,” Dr. Agarwal emphasized.
“My hope is not necessarily that physicians read this study and start using some or all of these codes more frequently,” said Dr. Agarwal. “It can be tempting to think of this as money left on the table, but it’s not; there are compliance, billing, and opportunity costs from using these codes,” he said. “For individual PCPs seeing individual patients for the breadth that is primary care, I’m not sure the juice is worth the squeeze,” he added. “My coauthors and I are all primary care physicians. We know from our research and first-hand that these codes can be cumbersome to use.” These codes also don’t reflect how PCPs practice, he said. “PCPs are not in the business of slicing and dicing a visit or patient to extract as much revenue as possible. The physician-patient interaction is more complex, and richer, than these codes imply. Instead, I hope our paper encourages Medicare and policymakers to take a harder look at other strategies for investing in primary care,” Dr. Agarwal added.
As for additional research, “Primary care spending is going in the wrong direction,” said Dr. Agarwal. “We need to figure out how best to finance primary care in the United States.”
Recent studies have examined the successes and limitations of the primary care medical home model, Medicare’s Comprehensive Primary Care Initiative, and primary care spending legislation, he said. “Our study is another piece of the puzzle: at least in its current form,” and the results suggest “that one-off codes were nice in theory but not in practice,” he noted.
New codes are cumbersome
“It’s tempting to interpret underuse of new billing codes as a simple change management problem,” Davoren Chick, MD, chief learning officer of the American College of Physicians, wrote in an accompanying editorial. However, the underuse of codes for preventive service and coordination of care likely stems from the details of the codes, he said.
The new codes require the documentation of specific components and a minimum duration of services, he explained. “Codes that reward discrete service episodes disadvantage physicians who appropriately integrate preventive services within a continuous patient care relationship,” he added.
Dr. Chick presented an example of a primary care physician who would have to deliver intensive behavioral therapy for obesity in 15-minute episodes outside of a routine office visit to meet the billing criteria for current Medicare codes.
Dr. Chick called on clinicians to educate themselves on the coding rules for the services they provide “not only to optimize current payment but also to advocate for change.”
He concluded: “Widespread underuse of new preventive service and coordination of care codes reflects system failure, not physician failure. We must stand firm with this knowledge to demand increased payment for feasible, patient-centered primary care commensurate with its value in achieving better outcomes and lower costs.”
The study was supported by the National Institute on Aging of the National Institutes of Health. Dr. Agarwal and Dr. Chick had no financial conflicts to disclose.
FROM ANNALS OF INTERNAL MEDICINE
For the Fourth of July, a neuroscientist reflects on patriotism
This week, we celebrate our nation’s birth in a national and individual display of our patriotic attachment to this country. — which includes our self-definition as Americans.
For each of us, personhood is an almost miraculous product of our brain’s plasticity — the brain’s ability to change chemically, structurally, and functionally, based on our life experiences — arising from near countless moments of change in the wiring of our brain.
The incredibly complex remodeling that created “you” is a product, of course, of your very complicated, unique passage in life. You have a repertoire of skills and ability; you have stories and understanding and a history of sensing and acting and thinking in the world that is, in detail, unique only to you and your experiences.
As your brain created its model of your world by recording “what goes with what” at each brief moment of time, your brain — that most complicated and wonderful of “machines” on planet Earth — also associated billions of moments of feeling and action and thought with their source, your Self.
Because we primarily construct our model of the world through our eyes and ears, it’s not surprising that the emergent Self that is located somewhere in the center of your head behind your eyes and between your ears. Through billions of contacts with the surfaces of your hide and sensory organs, you have embodied yourself.
Your sense of ‘us’
These same neurologic processes extend beyond our physical beings to incorporate other contributors to our well-being into our personhoods. Loving parents, siblings, friends — and others in your clans and tribes and nations — literally grow into your personhood by these same self-associating processes. These relationships are supported in mutual identity by all of the tokens and icons and charms and customs that collectively define you and enable a sense of “us.”
Put another way, Mother Nature (or, in another cultural perspective, our Creator) has designed our brains to incorporate all of those who are close to us — and more broadly, other individuals in our clan or tribe or nation — to be a part of each of us.
Humans are highly social creatures. When we rise up and risk our lives to defend our friends, family, or cultural “in-groups,” we are literally fighting to defend ourselves — because those other individuals have grown into our very being. In defending them, we are literally defending a part of ourselves.
From one human perspective, this attachment to family and clan and tribe and nation is obviously key for our survival. We are an individually vulnerable but collectively powerful species, and attachment and mutual support are a key to our personal and collective successes in life.
From another perspective, there is also a dark side to this “gift of nature.”
We draw lines in substantially arbitrary locations across the surface of planet Earth, or we may define our self as belonging to a group in a political or social or religious context, or sect. Our tribalism can support a generally strong level of support and succor for fellow humans on our side of that line, while we regard those just across the line as undeserving of our support. If they offend us, they may become targets of our capacity for cruelty.
Our allegiances can be both wonderful and harmful.
The individuality of us
As we celebrate this holiday — a favorite day on my personal calendar — I am compelled to reflect on the fact that America was designed to be fractious. We Americans are not required to all operate like “peas in the pod.”
While we, as a nation, often fail to live up to our ideals, when we pursue the highest standards of liberty, we celebrate diversity, difference, and the ability of each member of our tribe to find their own path.
In a very real sense, the great American “invention” was to create a nation in which we could all find a wonderful place of our own, with the sympathy and protection of fellow citizens, and with liberty and justice for all.
Happy Independence Day to my American tribe!
Michael Merzenich, PhD, is often credited with discovering lifelong plasticity, with being the first to harness plasticity for human benefit (in his co-invention of the cochlear implant), and for pioneering the field of plasticity-based computerized brain exercise. He is professor emeritus at UCSF and a Kavli Laureate in Neuroscience, and he has been honored by each of the US National Academies of Sciences, Engineering, and Medicine. He may be most widely known for a series of specials on the brain on public television. His current focus is BrainHQ, a brain exercise app. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Posit Science Corporation; Stronger Brains Inc. Serve(d) as a speaker or a member of a speakers bureau for: Posit Science Corporation; Stronger Brains Inc. Received research grant from: National Institutes of Health Have a 5% or greater equity interest in: Posit Science Corporation; Stronger Brains Inc. Received income in an amount equal to or greater than $250 from: Posit Science Corporation; Stronger Brains Inc.; National Institutes of Health.
A version of this article first appeared on Medscape.com.
This week, we celebrate our nation’s birth in a national and individual display of our patriotic attachment to this country. — which includes our self-definition as Americans.
For each of us, personhood is an almost miraculous product of our brain’s plasticity — the brain’s ability to change chemically, structurally, and functionally, based on our life experiences — arising from near countless moments of change in the wiring of our brain.
The incredibly complex remodeling that created “you” is a product, of course, of your very complicated, unique passage in life. You have a repertoire of skills and ability; you have stories and understanding and a history of sensing and acting and thinking in the world that is, in detail, unique only to you and your experiences.
As your brain created its model of your world by recording “what goes with what” at each brief moment of time, your brain — that most complicated and wonderful of “machines” on planet Earth — also associated billions of moments of feeling and action and thought with their source, your Self.
Because we primarily construct our model of the world through our eyes and ears, it’s not surprising that the emergent Self that is located somewhere in the center of your head behind your eyes and between your ears. Through billions of contacts with the surfaces of your hide and sensory organs, you have embodied yourself.
Your sense of ‘us’
These same neurologic processes extend beyond our physical beings to incorporate other contributors to our well-being into our personhoods. Loving parents, siblings, friends — and others in your clans and tribes and nations — literally grow into your personhood by these same self-associating processes. These relationships are supported in mutual identity by all of the tokens and icons and charms and customs that collectively define you and enable a sense of “us.”
Put another way, Mother Nature (or, in another cultural perspective, our Creator) has designed our brains to incorporate all of those who are close to us — and more broadly, other individuals in our clan or tribe or nation — to be a part of each of us.
Humans are highly social creatures. When we rise up and risk our lives to defend our friends, family, or cultural “in-groups,” we are literally fighting to defend ourselves — because those other individuals have grown into our very being. In defending them, we are literally defending a part of ourselves.
From one human perspective, this attachment to family and clan and tribe and nation is obviously key for our survival. We are an individually vulnerable but collectively powerful species, and attachment and mutual support are a key to our personal and collective successes in life.
From another perspective, there is also a dark side to this “gift of nature.”
We draw lines in substantially arbitrary locations across the surface of planet Earth, or we may define our self as belonging to a group in a political or social or religious context, or sect. Our tribalism can support a generally strong level of support and succor for fellow humans on our side of that line, while we regard those just across the line as undeserving of our support. If they offend us, they may become targets of our capacity for cruelty.
Our allegiances can be both wonderful and harmful.
The individuality of us
As we celebrate this holiday — a favorite day on my personal calendar — I am compelled to reflect on the fact that America was designed to be fractious. We Americans are not required to all operate like “peas in the pod.”
While we, as a nation, often fail to live up to our ideals, when we pursue the highest standards of liberty, we celebrate diversity, difference, and the ability of each member of our tribe to find their own path.
In a very real sense, the great American “invention” was to create a nation in which we could all find a wonderful place of our own, with the sympathy and protection of fellow citizens, and with liberty and justice for all.
Happy Independence Day to my American tribe!
Michael Merzenich, PhD, is often credited with discovering lifelong plasticity, with being the first to harness plasticity for human benefit (in his co-invention of the cochlear implant), and for pioneering the field of plasticity-based computerized brain exercise. He is professor emeritus at UCSF and a Kavli Laureate in Neuroscience, and he has been honored by each of the US National Academies of Sciences, Engineering, and Medicine. He may be most widely known for a series of specials on the brain on public television. His current focus is BrainHQ, a brain exercise app. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Posit Science Corporation; Stronger Brains Inc. Serve(d) as a speaker or a member of a speakers bureau for: Posit Science Corporation; Stronger Brains Inc. Received research grant from: National Institutes of Health Have a 5% or greater equity interest in: Posit Science Corporation; Stronger Brains Inc. Received income in an amount equal to or greater than $250 from: Posit Science Corporation; Stronger Brains Inc.; National Institutes of Health.
A version of this article first appeared on Medscape.com.
This week, we celebrate our nation’s birth in a national and individual display of our patriotic attachment to this country. — which includes our self-definition as Americans.
For each of us, personhood is an almost miraculous product of our brain’s plasticity — the brain’s ability to change chemically, structurally, and functionally, based on our life experiences — arising from near countless moments of change in the wiring of our brain.
The incredibly complex remodeling that created “you” is a product, of course, of your very complicated, unique passage in life. You have a repertoire of skills and ability; you have stories and understanding and a history of sensing and acting and thinking in the world that is, in detail, unique only to you and your experiences.
As your brain created its model of your world by recording “what goes with what” at each brief moment of time, your brain — that most complicated and wonderful of “machines” on planet Earth — also associated billions of moments of feeling and action and thought with their source, your Self.
Because we primarily construct our model of the world through our eyes and ears, it’s not surprising that the emergent Self that is located somewhere in the center of your head behind your eyes and between your ears. Through billions of contacts with the surfaces of your hide and sensory organs, you have embodied yourself.
Your sense of ‘us’
These same neurologic processes extend beyond our physical beings to incorporate other contributors to our well-being into our personhoods. Loving parents, siblings, friends — and others in your clans and tribes and nations — literally grow into your personhood by these same self-associating processes. These relationships are supported in mutual identity by all of the tokens and icons and charms and customs that collectively define you and enable a sense of “us.”
Put another way, Mother Nature (or, in another cultural perspective, our Creator) has designed our brains to incorporate all of those who are close to us — and more broadly, other individuals in our clan or tribe or nation — to be a part of each of us.
Humans are highly social creatures. When we rise up and risk our lives to defend our friends, family, or cultural “in-groups,” we are literally fighting to defend ourselves — because those other individuals have grown into our very being. In defending them, we are literally defending a part of ourselves.
From one human perspective, this attachment to family and clan and tribe and nation is obviously key for our survival. We are an individually vulnerable but collectively powerful species, and attachment and mutual support are a key to our personal and collective successes in life.
From another perspective, there is also a dark side to this “gift of nature.”
We draw lines in substantially arbitrary locations across the surface of planet Earth, or we may define our self as belonging to a group in a political or social or religious context, or sect. Our tribalism can support a generally strong level of support and succor for fellow humans on our side of that line, while we regard those just across the line as undeserving of our support. If they offend us, they may become targets of our capacity for cruelty.
Our allegiances can be both wonderful and harmful.
The individuality of us
As we celebrate this holiday — a favorite day on my personal calendar — I am compelled to reflect on the fact that America was designed to be fractious. We Americans are not required to all operate like “peas in the pod.”
While we, as a nation, often fail to live up to our ideals, when we pursue the highest standards of liberty, we celebrate diversity, difference, and the ability of each member of our tribe to find their own path.
In a very real sense, the great American “invention” was to create a nation in which we could all find a wonderful place of our own, with the sympathy and protection of fellow citizens, and with liberty and justice for all.
Happy Independence Day to my American tribe!
Michael Merzenich, PhD, is often credited with discovering lifelong plasticity, with being the first to harness plasticity for human benefit (in his co-invention of the cochlear implant), and for pioneering the field of plasticity-based computerized brain exercise. He is professor emeritus at UCSF and a Kavli Laureate in Neuroscience, and he has been honored by each of the US National Academies of Sciences, Engineering, and Medicine. He may be most widely known for a series of specials on the brain on public television. His current focus is BrainHQ, a brain exercise app. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Posit Science Corporation; Stronger Brains Inc. Serve(d) as a speaker or a member of a speakers bureau for: Posit Science Corporation; Stronger Brains Inc. Received research grant from: National Institutes of Health Have a 5% or greater equity interest in: Posit Science Corporation; Stronger Brains Inc. Received income in an amount equal to or greater than $250 from: Posit Science Corporation; Stronger Brains Inc.; National Institutes of Health.
A version of this article first appeared on Medscape.com.
Commentary: Recent Chemotherapy Regimen Trial Results, July 2022
The TRIPLETE study from Italy is a simply designed phase 3 clinical trial in which 435 patients with newly diagnosed RAS and BRAF wild-type metastatic colorectal cancer were randomized in a 1:1 fashionto receive either modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) plus panitumumab or fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) plus panitumumab. In both arms, over 90% of patients were aged ≤70 years old, and 12% had right-sided disease. These factors are critical because older patients are less likely to benefit from multidrug chemotherapy, and patients with right-sided disease would not be expected to respond to epidermal growth factor receptor inhibitors, irrespective of RAS status. The study's primary endpoint was objective response rate (ORR) according to the revised Response Evaluation Criteria in Solid Tumours guidelines (RECIST 1.1). Secondary endpoints included safety and progression-free survival (PFS). ORR was 73% in the experimental arm and 76% in the control arm (odds ratio [OR] 0.87; P = .526). There were no differences in PFS, early tumor shrinkage rate, R0 resection rate, or depth of response either.
Though I would have liked to have seen a leucovorin calcium (folinic acid), fluorouracil,and irinotecan hydrochloride (FOLFIRI) arm as well, I believe that these results are enough to cast significant doubt on the burgeoning belief that in metastatic colorectal cancer, more chemotherapy is better for those who can tolerate it.
AtezoTRIBE, also out of Italy, is a randomized, phase 2 study that randomly selected patients with newly diagnosed metastatic colorectal cancer to receive FOLFOXIRI and bevacizumab with or without atezolizumab. I am less sanguine about this study design, vis-à-vis the TRIPLETE study, as patients in AtezoTRIBE were randomized in a 2:1 fashion, with two thirds therefore receiving treatment on the experimental arm. The 2:1 randomization was rationalized on the basis of the supposition that patients are more likely to enroll on a study if they know they have a greater chance of receiving a novel treatment. However, I have never seen a study supporting that hypothesis with data, and a 2:1 randomization significantly reduces statistical power. Patients were stratified on the basis of tumor mutational burden (TMB) and Immunoscore IC (high or low as determined by CD8 cell density, programmed death ligand 1 cell density, as well as proximity and clustering of the two cell groups). There were similar rates of high TMB (7% control and 8% experimental) and high Immunoscore IC (25% control and 22% experimental) in both arms. The primary endpoint was PFS. At a median follow-up of 19.9 months, the experimental arm had astatistically improved median PFS (13.1 vs 11.5 months; adjusted hazard ratio 0.70; P = .018). Serious adverse events were reported in 27% vs 26% of patients, respectively. Of note, the subgroup analysis shows that PFS improvement was accrued in the experimental arm by patients with either high TMB, high Immunoscore IC, or both. Further studies will be needed in patients prospectively selected for high Immunoscore IC to see whether these observations hold. If so, Immunoscore IC could eventually replace TMB as a marker of potential immune therapy responsiveness in microsatellite-stable metastatic colorectal cancer.
The TRIPLETE study from Italy is a simply designed phase 3 clinical trial in which 435 patients with newly diagnosed RAS and BRAF wild-type metastatic colorectal cancer were randomized in a 1:1 fashionto receive either modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) plus panitumumab or fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) plus panitumumab. In both arms, over 90% of patients were aged ≤70 years old, and 12% had right-sided disease. These factors are critical because older patients are less likely to benefit from multidrug chemotherapy, and patients with right-sided disease would not be expected to respond to epidermal growth factor receptor inhibitors, irrespective of RAS status. The study's primary endpoint was objective response rate (ORR) according to the revised Response Evaluation Criteria in Solid Tumours guidelines (RECIST 1.1). Secondary endpoints included safety and progression-free survival (PFS). ORR was 73% in the experimental arm and 76% in the control arm (odds ratio [OR] 0.87; P = .526). There were no differences in PFS, early tumor shrinkage rate, R0 resection rate, or depth of response either.
Though I would have liked to have seen a leucovorin calcium (folinic acid), fluorouracil,and irinotecan hydrochloride (FOLFIRI) arm as well, I believe that these results are enough to cast significant doubt on the burgeoning belief that in metastatic colorectal cancer, more chemotherapy is better for those who can tolerate it.
AtezoTRIBE, also out of Italy, is a randomized, phase 2 study that randomly selected patients with newly diagnosed metastatic colorectal cancer to receive FOLFOXIRI and bevacizumab with or without atezolizumab. I am less sanguine about this study design, vis-à-vis the TRIPLETE study, as patients in AtezoTRIBE were randomized in a 2:1 fashion, with two thirds therefore receiving treatment on the experimental arm. The 2:1 randomization was rationalized on the basis of the supposition that patients are more likely to enroll on a study if they know they have a greater chance of receiving a novel treatment. However, I have never seen a study supporting that hypothesis with data, and a 2:1 randomization significantly reduces statistical power. Patients were stratified on the basis of tumor mutational burden (TMB) and Immunoscore IC (high or low as determined by CD8 cell density, programmed death ligand 1 cell density, as well as proximity and clustering of the two cell groups). There were similar rates of high TMB (7% control and 8% experimental) and high Immunoscore IC (25% control and 22% experimental) in both arms. The primary endpoint was PFS. At a median follow-up of 19.9 months, the experimental arm had astatistically improved median PFS (13.1 vs 11.5 months; adjusted hazard ratio 0.70; P = .018). Serious adverse events were reported in 27% vs 26% of patients, respectively. Of note, the subgroup analysis shows that PFS improvement was accrued in the experimental arm by patients with either high TMB, high Immunoscore IC, or both. Further studies will be needed in patients prospectively selected for high Immunoscore IC to see whether these observations hold. If so, Immunoscore IC could eventually replace TMB as a marker of potential immune therapy responsiveness in microsatellite-stable metastatic colorectal cancer.
The TRIPLETE study from Italy is a simply designed phase 3 clinical trial in which 435 patients with newly diagnosed RAS and BRAF wild-type metastatic colorectal cancer were randomized in a 1:1 fashionto receive either modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) plus panitumumab or fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) plus panitumumab. In both arms, over 90% of patients were aged ≤70 years old, and 12% had right-sided disease. These factors are critical because older patients are less likely to benefit from multidrug chemotherapy, and patients with right-sided disease would not be expected to respond to epidermal growth factor receptor inhibitors, irrespective of RAS status. The study's primary endpoint was objective response rate (ORR) according to the revised Response Evaluation Criteria in Solid Tumours guidelines (RECIST 1.1). Secondary endpoints included safety and progression-free survival (PFS). ORR was 73% in the experimental arm and 76% in the control arm (odds ratio [OR] 0.87; P = .526). There were no differences in PFS, early tumor shrinkage rate, R0 resection rate, or depth of response either.
Though I would have liked to have seen a leucovorin calcium (folinic acid), fluorouracil,and irinotecan hydrochloride (FOLFIRI) arm as well, I believe that these results are enough to cast significant doubt on the burgeoning belief that in metastatic colorectal cancer, more chemotherapy is better for those who can tolerate it.
AtezoTRIBE, also out of Italy, is a randomized, phase 2 study that randomly selected patients with newly diagnosed metastatic colorectal cancer to receive FOLFOXIRI and bevacizumab with or without atezolizumab. I am less sanguine about this study design, vis-à-vis the TRIPLETE study, as patients in AtezoTRIBE were randomized in a 2:1 fashion, with two thirds therefore receiving treatment on the experimental arm. The 2:1 randomization was rationalized on the basis of the supposition that patients are more likely to enroll on a study if they know they have a greater chance of receiving a novel treatment. However, I have never seen a study supporting that hypothesis with data, and a 2:1 randomization significantly reduces statistical power. Patients were stratified on the basis of tumor mutational burden (TMB) and Immunoscore IC (high or low as determined by CD8 cell density, programmed death ligand 1 cell density, as well as proximity and clustering of the two cell groups). There were similar rates of high TMB (7% control and 8% experimental) and high Immunoscore IC (25% control and 22% experimental) in both arms. The primary endpoint was PFS. At a median follow-up of 19.9 months, the experimental arm had astatistically improved median PFS (13.1 vs 11.5 months; adjusted hazard ratio 0.70; P = .018). Serious adverse events were reported in 27% vs 26% of patients, respectively. Of note, the subgroup analysis shows that PFS improvement was accrued in the experimental arm by patients with either high TMB, high Immunoscore IC, or both. Further studies will be needed in patients prospectively selected for high Immunoscore IC to see whether these observations hold. If so, Immunoscore IC could eventually replace TMB as a marker of potential immune therapy responsiveness in microsatellite-stable metastatic colorectal cancer.
Commentary: Benefits of GLP-1 Receptor Agonists and Studies of Continuous Glucose Monitoring, July 2022
Research continues to demonstrate the benefits of glucagon-like peptide-1 receptor (GLP-1R) agonists or co-agonists for type 2 diabetes (T2D). Arslanian and the AWARD-PEDS investigators have published the results of a randomized controlled trial comparing once-weekly dulaglutide vs.placebo in youths between 10 and17 years of age with T2D. A1c was reduced by 1.2% with 0.75 mg dulaglutide and by 1.5% with a 1.5 mg dose, compared with placebo. Of note, there was no significant weight difference between dulaglutide and placebo, similar to what has been found with liraglutide and extended-release exenatide in similar populations. This is also contrary to the weight loss that is found with GLP-1R agonists in adult studies. While the GLP-1R agonist class provides a nice glycemic benefit in youth with T2D, it remains perplexing as to why weight loss has not been demonstrated in clinical trials.
In the SURPASS trials of the GLP-1/gastric inhibitory polypeptide (GIP) receptor co-agonist tirzepatide, there was robust A1c lowering and weight loss among individuals with T2D. A meta-analysis published by Karagiannis and colleagues of seven tirzepatide trials has shown dose-dependent superiority for A1c and weight compared withplacebo, GLP-1R agonists, and basal insulin. Gastrointestinal side effects were similar to what we have come to expect with GLP-1R agonist–based therapies. Tirzepatide, recently approved by the US Food and Drug Administration (FDA) for the treatment of T2D, is a welcome addition to the pharmacotherapy toolkit.
In the SURPASS-2 study, all doses of tirzepatide were superior to 1 mg semaglutide for both A1c and body weight reduction. Following the recent approval of 2 mg semaglutide by the FDA for the management of T2D, Vadher and colleagues explored how tirzepatide compares with 2 mg semaglutide via an indirect treatment comparison. Using data from the SUSTAIN-FORTE and SURPASS-2 trials, these authors found that A1c and weight reductions were significantly greater for 10 and 15 mg tirzepatide vs 2 mg semaglutide and similar for 5 mg tirzepatide vs 2 mg semaglutide. In the absence of a head-to-head trial, this analysis suggests greater efficacy with tirzepatide compared with high-dose semaglutide in T2D.
Continuous glucose monitoring (CGM) provides information about glycemia that is not available with A1c and capillary glucose monitoring. The coefficient of variation (CV) calculated from CGM is a good measure of glycemic variability, with a goal of ≤36%. There are inconsistent data for the association of CV with microvascular or macrovascular complications and very little study of the relationship between CV and long-term mortality. Mo and colleagues investigated the association between short-term glycemic variability measured by CV and all-cause mortality in a prospective study of 1839 individuals with T2D and a well-controlled glucose profile monitored by CGM. After about 7 years of follow-up, a greater baseline CV was associated with an increased risk for all-cause mortality, with a greater than twofold risk fo rmortality with a baseline CV of >35% compared witha baseline CV of ≤20%. This study suggests that clinicians should pay attention when CV is high, even with otherwise good glycemic control. With the expanding use of CGM, long-term intervention studies are needed to determine the role of glycemic variability(CV) in the development of complications and hard outcomes.
Research continues to demonstrate the benefits of glucagon-like peptide-1 receptor (GLP-1R) agonists or co-agonists for type 2 diabetes (T2D). Arslanian and the AWARD-PEDS investigators have published the results of a randomized controlled trial comparing once-weekly dulaglutide vs.placebo in youths between 10 and17 years of age with T2D. A1c was reduced by 1.2% with 0.75 mg dulaglutide and by 1.5% with a 1.5 mg dose, compared with placebo. Of note, there was no significant weight difference between dulaglutide and placebo, similar to what has been found with liraglutide and extended-release exenatide in similar populations. This is also contrary to the weight loss that is found with GLP-1R agonists in adult studies. While the GLP-1R agonist class provides a nice glycemic benefit in youth with T2D, it remains perplexing as to why weight loss has not been demonstrated in clinical trials.
In the SURPASS trials of the GLP-1/gastric inhibitory polypeptide (GIP) receptor co-agonist tirzepatide, there was robust A1c lowering and weight loss among individuals with T2D. A meta-analysis published by Karagiannis and colleagues of seven tirzepatide trials has shown dose-dependent superiority for A1c and weight compared withplacebo, GLP-1R agonists, and basal insulin. Gastrointestinal side effects were similar to what we have come to expect with GLP-1R agonist–based therapies. Tirzepatide, recently approved by the US Food and Drug Administration (FDA) for the treatment of T2D, is a welcome addition to the pharmacotherapy toolkit.
In the SURPASS-2 study, all doses of tirzepatide were superior to 1 mg semaglutide for both A1c and body weight reduction. Following the recent approval of 2 mg semaglutide by the FDA for the management of T2D, Vadher and colleagues explored how tirzepatide compares with 2 mg semaglutide via an indirect treatment comparison. Using data from the SUSTAIN-FORTE and SURPASS-2 trials, these authors found that A1c and weight reductions were significantly greater for 10 and 15 mg tirzepatide vs 2 mg semaglutide and similar for 5 mg tirzepatide vs 2 mg semaglutide. In the absence of a head-to-head trial, this analysis suggests greater efficacy with tirzepatide compared with high-dose semaglutide in T2D.
Continuous glucose monitoring (CGM) provides information about glycemia that is not available with A1c and capillary glucose monitoring. The coefficient of variation (CV) calculated from CGM is a good measure of glycemic variability, with a goal of ≤36%. There are inconsistent data for the association of CV with microvascular or macrovascular complications and very little study of the relationship between CV and long-term mortality. Mo and colleagues investigated the association between short-term glycemic variability measured by CV and all-cause mortality in a prospective study of 1839 individuals with T2D and a well-controlled glucose profile monitored by CGM. After about 7 years of follow-up, a greater baseline CV was associated with an increased risk for all-cause mortality, with a greater than twofold risk fo rmortality with a baseline CV of >35% compared witha baseline CV of ≤20%. This study suggests that clinicians should pay attention when CV is high, even with otherwise good glycemic control. With the expanding use of CGM, long-term intervention studies are needed to determine the role of glycemic variability(CV) in the development of complications and hard outcomes.
Research continues to demonstrate the benefits of glucagon-like peptide-1 receptor (GLP-1R) agonists or co-agonists for type 2 diabetes (T2D). Arslanian and the AWARD-PEDS investigators have published the results of a randomized controlled trial comparing once-weekly dulaglutide vs.placebo in youths between 10 and17 years of age with T2D. A1c was reduced by 1.2% with 0.75 mg dulaglutide and by 1.5% with a 1.5 mg dose, compared with placebo. Of note, there was no significant weight difference between dulaglutide and placebo, similar to what has been found with liraglutide and extended-release exenatide in similar populations. This is also contrary to the weight loss that is found with GLP-1R agonists in adult studies. While the GLP-1R agonist class provides a nice glycemic benefit in youth with T2D, it remains perplexing as to why weight loss has not been demonstrated in clinical trials.
In the SURPASS trials of the GLP-1/gastric inhibitory polypeptide (GIP) receptor co-agonist tirzepatide, there was robust A1c lowering and weight loss among individuals with T2D. A meta-analysis published by Karagiannis and colleagues of seven tirzepatide trials has shown dose-dependent superiority for A1c and weight compared withplacebo, GLP-1R agonists, and basal insulin. Gastrointestinal side effects were similar to what we have come to expect with GLP-1R agonist–based therapies. Tirzepatide, recently approved by the US Food and Drug Administration (FDA) for the treatment of T2D, is a welcome addition to the pharmacotherapy toolkit.
In the SURPASS-2 study, all doses of tirzepatide were superior to 1 mg semaglutide for both A1c and body weight reduction. Following the recent approval of 2 mg semaglutide by the FDA for the management of T2D, Vadher and colleagues explored how tirzepatide compares with 2 mg semaglutide via an indirect treatment comparison. Using data from the SUSTAIN-FORTE and SURPASS-2 trials, these authors found that A1c and weight reductions were significantly greater for 10 and 15 mg tirzepatide vs 2 mg semaglutide and similar for 5 mg tirzepatide vs 2 mg semaglutide. In the absence of a head-to-head trial, this analysis suggests greater efficacy with tirzepatide compared with high-dose semaglutide in T2D.
Continuous glucose monitoring (CGM) provides information about glycemia that is not available with A1c and capillary glucose monitoring. The coefficient of variation (CV) calculated from CGM is a good measure of glycemic variability, with a goal of ≤36%. There are inconsistent data for the association of CV with microvascular or macrovascular complications and very little study of the relationship between CV and long-term mortality. Mo and colleagues investigated the association between short-term glycemic variability measured by CV and all-cause mortality in a prospective study of 1839 individuals with T2D and a well-controlled glucose profile monitored by CGM. After about 7 years of follow-up, a greater baseline CV was associated with an increased risk for all-cause mortality, with a greater than twofold risk fo rmortality with a baseline CV of >35% compared witha baseline CV of ≤20%. This study suggests that clinicians should pay attention when CV is high, even with otherwise good glycemic control. With the expanding use of CGM, long-term intervention studies are needed to determine the role of glycemic variability(CV) in the development of complications and hard outcomes.
Genetic ‘taste score’ could help us eat healthier and reduce disease risk
Addicted to cookies? Can’t stand broccoli? You may be able to blame Mom and Dad.
That’s because our taste preferences are influenced by our genes. And this may play an important role in determining our food choices and, in turn, our health, according to early study findings presented at this year’s annual meeting of the American Society for Nutrition.
“Our genetic predispositions to perceive certain tastes might be one of many reasons why some of us struggle to make healthy food choices,” says the study’s lead researcher, Julie Gervis, a doctoral degree candidate at the Tufts Jean Mayer USDA Human Nutrition Research Center on Aging.
As the field of personalized nutrition – a branch of science that uses technology to help people figure out what to eat for good health – advances, the findings could bring us closer to more effective personalized nutrition advice, better diets, and less risk for things like obesity, type 2 diabetes, and heart disease.
What’s your ‘polygenic taste score’?
We know genes influence our taste, but little is known about how taste-related genes impact diet quality and health. To investigate this, the researchers used data from “genome-wide association studies,” which scientists use to find gene variations associated with a trait, to create something called a polygenic taste score.
Your polygenic taste score shows how your genes impact your unique perception of taste – be it bitter, salty, sweet, sour, or savory (umami). If you have a high score for, say, sweet, that means you may be more sensitive to sweetness than someone with a moderate or low sweet score.
In the study sample of more than 6,000 adults, those with a high “bitter” score tended to eat fewer whole grains (two fewer servings a week), while those scoring high for savory ate fewer vegetables, especially orange and red types like carrots and bell peppers. That matters because whole grains have been shown to reduce heart disease risk, while a higher veggie intake is linked to lower risk of type 2 diabetes.
Meanwhile, genes related to sweet seemed key for health related to your heart and metabolism, as a higher sweet score was linked with lower triglycerides, a type of fat found in the blood.
From lab to shopping list
While we have a long way to go before dietitians and consumers can use polygenic taste scores, the tool could one day help us use – or minimize – the influence our genes has on our food choices, Ms. Gervis says. That may help us improve personalized nutrition advice aimed at reducing disease risk.
But first, other research needs to repeat the findings, Ms. Gervis says. And more large-scale, genome-wide studies on taste perception should be done.
“I hope these preliminary data convey the potential benefit of incorporating taste-related genes, and taste perception, into personalized nutrition,” she says. “After all, while we don’t always choose what foods are good for us, we do always choose what foods taste good to us.”
A version of this article first appeared on WebMD.com.
Addicted to cookies? Can’t stand broccoli? You may be able to blame Mom and Dad.
That’s because our taste preferences are influenced by our genes. And this may play an important role in determining our food choices and, in turn, our health, according to early study findings presented at this year’s annual meeting of the American Society for Nutrition.
“Our genetic predispositions to perceive certain tastes might be one of many reasons why some of us struggle to make healthy food choices,” says the study’s lead researcher, Julie Gervis, a doctoral degree candidate at the Tufts Jean Mayer USDA Human Nutrition Research Center on Aging.
As the field of personalized nutrition – a branch of science that uses technology to help people figure out what to eat for good health – advances, the findings could bring us closer to more effective personalized nutrition advice, better diets, and less risk for things like obesity, type 2 diabetes, and heart disease.
What’s your ‘polygenic taste score’?
We know genes influence our taste, but little is known about how taste-related genes impact diet quality and health. To investigate this, the researchers used data from “genome-wide association studies,” which scientists use to find gene variations associated with a trait, to create something called a polygenic taste score.
Your polygenic taste score shows how your genes impact your unique perception of taste – be it bitter, salty, sweet, sour, or savory (umami). If you have a high score for, say, sweet, that means you may be more sensitive to sweetness than someone with a moderate or low sweet score.
In the study sample of more than 6,000 adults, those with a high “bitter” score tended to eat fewer whole grains (two fewer servings a week), while those scoring high for savory ate fewer vegetables, especially orange and red types like carrots and bell peppers. That matters because whole grains have been shown to reduce heart disease risk, while a higher veggie intake is linked to lower risk of type 2 diabetes.
Meanwhile, genes related to sweet seemed key for health related to your heart and metabolism, as a higher sweet score was linked with lower triglycerides, a type of fat found in the blood.
From lab to shopping list
While we have a long way to go before dietitians and consumers can use polygenic taste scores, the tool could one day help us use – or minimize – the influence our genes has on our food choices, Ms. Gervis says. That may help us improve personalized nutrition advice aimed at reducing disease risk.
But first, other research needs to repeat the findings, Ms. Gervis says. And more large-scale, genome-wide studies on taste perception should be done.
“I hope these preliminary data convey the potential benefit of incorporating taste-related genes, and taste perception, into personalized nutrition,” she says. “After all, while we don’t always choose what foods are good for us, we do always choose what foods taste good to us.”
A version of this article first appeared on WebMD.com.
Addicted to cookies? Can’t stand broccoli? You may be able to blame Mom and Dad.
That’s because our taste preferences are influenced by our genes. And this may play an important role in determining our food choices and, in turn, our health, according to early study findings presented at this year’s annual meeting of the American Society for Nutrition.
“Our genetic predispositions to perceive certain tastes might be one of many reasons why some of us struggle to make healthy food choices,” says the study’s lead researcher, Julie Gervis, a doctoral degree candidate at the Tufts Jean Mayer USDA Human Nutrition Research Center on Aging.
As the field of personalized nutrition – a branch of science that uses technology to help people figure out what to eat for good health – advances, the findings could bring us closer to more effective personalized nutrition advice, better diets, and less risk for things like obesity, type 2 diabetes, and heart disease.
What’s your ‘polygenic taste score’?
We know genes influence our taste, but little is known about how taste-related genes impact diet quality and health. To investigate this, the researchers used data from “genome-wide association studies,” which scientists use to find gene variations associated with a trait, to create something called a polygenic taste score.
Your polygenic taste score shows how your genes impact your unique perception of taste – be it bitter, salty, sweet, sour, or savory (umami). If you have a high score for, say, sweet, that means you may be more sensitive to sweetness than someone with a moderate or low sweet score.
In the study sample of more than 6,000 adults, those with a high “bitter” score tended to eat fewer whole grains (two fewer servings a week), while those scoring high for savory ate fewer vegetables, especially orange and red types like carrots and bell peppers. That matters because whole grains have been shown to reduce heart disease risk, while a higher veggie intake is linked to lower risk of type 2 diabetes.
Meanwhile, genes related to sweet seemed key for health related to your heart and metabolism, as a higher sweet score was linked with lower triglycerides, a type of fat found in the blood.
From lab to shopping list
While we have a long way to go before dietitians and consumers can use polygenic taste scores, the tool could one day help us use – or minimize – the influence our genes has on our food choices, Ms. Gervis says. That may help us improve personalized nutrition advice aimed at reducing disease risk.
But first, other research needs to repeat the findings, Ms. Gervis says. And more large-scale, genome-wide studies on taste perception should be done.
“I hope these preliminary data convey the potential benefit of incorporating taste-related genes, and taste perception, into personalized nutrition,” she says. “After all, while we don’t always choose what foods are good for us, we do always choose what foods taste good to us.”
A version of this article first appeared on WebMD.com.
Cancer may increase risk of type 2 diabetes
most notably pancreatic malignancies.
“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.
“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
Diabetes risk highest with pancreatic cancer
Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.
Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis.
They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).
The link with pancreatic cancer was not surprising, said Dr. Sylow.
Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.
The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.
In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.
“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
Increased mortality risk in those with cancer and type 2 diabetes
Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.
“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.
Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.
Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.
Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.
Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
most notably pancreatic malignancies.
“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.
“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
Diabetes risk highest with pancreatic cancer
Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.
Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis.
They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).
The link with pancreatic cancer was not surprising, said Dr. Sylow.
Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.
The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.
In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.
“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
Increased mortality risk in those with cancer and type 2 diabetes
Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.
“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.
Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.
Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.
Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.
Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
most notably pancreatic malignancies.
“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.
“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
Diabetes risk highest with pancreatic cancer
Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.
Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis.
They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).
The link with pancreatic cancer was not surprising, said Dr. Sylow.
Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.
The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.
In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.
“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
Increased mortality risk in those with cancer and type 2 diabetes
Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.
“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.
Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.
Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.
Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.
Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE