Mental illness has been waiting in the wings for years; ignored, ridiculed, minimized, and stigmatized. Those who succumbed to it tried to lend testimonials, but to no avail. Those who were spared its effects remained in disbelief. So, it stayed on the sidelines, growing in intensity and breadth, yet stifled by the masses, until 2 years ago.

In March 2020, when COVID-19 became a pandemic, the importance of mental health finally became undeniable. As the pandemic’s effects progressed and wreaked havoc on our nation, our mental illness rates simultaneously surged. This surge paralleled that of the COVID-19 pandemic’s and in fact, contributed to a secondary crisis, allowing mental health to finally be addressed and gain center stage status.

But “mental health” is not easily defined, as it takes on many forms and is expressed in a variety of ways and via a myriad of symptoms. It does not discriminate by gender, race, age, socioeconomic status, educational level, profession, religion, or geography. At times, mental health status is consistent but at other times it can fluctuate in intensity, duration, and expression. It can be difficult to manage, yet there are various treatment modalities that can be implemented to lessen the impact of mental illness. Stressful events seem to potentiate its manifestation and yet, there are times it seems to appear spontaneously, much as an uninvited guest.

Mental health has a strong synergistic relationship with physical health, as they are very interdependent and allow us to function at our best only when they are both operating optimally. It should come as no surprise then, that the COVID-19 pandemic contributed to the exponential surge of mental illnesses. Capitalizing on its nondiscriminatory nature, mental illness impacted a large segment of the population – both those suffering from COVID-19 as well as those treating them.

As the nation starts to heal from the immediate and lingering physical and emotional consequences of the COVID-19 pandemic, President Biden has chosen to address and try to meet the needs of the health care heroes, the healers. The signing of H.R. 1667, the Dr. Lorna Breen Health Care Provider Protection Act into law on March 18, 2022, showed dedication to the health care community that has given tirelessly to our nation during the COVID-19 pandemic, and is itself recuperating from that effort.

Taking a top-down approach is essential to assuring the health of the nation. If our healers are not healthy, physically and mentally, they will not be able treat those whom they are dedicated to helping. Openly discussing and acknowledging the mental health problems of health care workers as a community makes it okay to not be okay. It normalizes the need for health care workers to prioritize their own mental health. It can also start to ease the fear of professional backlash or repercussions for practicing self-care.

I, for one, am very grateful for the prioritizing and promoting of the importance of mental health and wellness amongst health care workers. This helps to reduce the stigma of mental illness, helps us understand its impact, and allows us to formulate strategies and solutions to address its effects. The time has come.

Dr. Jarkon is a psychiatrist and director of the Center for Behavioral Health at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y.

Mental illness has been waiting in the wings for years; ignored, ridiculed, minimized, and stigmatized. Those who succumbed to it tried to lend testimonials, but to no avail. Those who were spared its effects remained in disbelief. So, it stayed on the sidelines, growing in intensity and breadth, yet stifled by the masses, until 2 years ago.

In March 2020, when COVID-19 became a pandemic, the importance of mental health finally became undeniable. As the pandemic’s effects progressed and wreaked havoc on our nation, our mental illness rates simultaneously surged. This surge paralleled that of the COVID-19 pandemic’s and in fact, contributed to a secondary crisis, allowing mental health to finally be addressed and gain center stage status.

But “mental health” is not easily defined, as it takes on many forms and is expressed in a variety of ways and via a myriad of symptoms. It does not discriminate by gender, race, age, socioeconomic status, educational level, profession, religion, or geography. At times, mental health status is consistent but at other times it can fluctuate in intensity, duration, and expression. It can be difficult to manage, yet there are various treatment modalities that can be implemented to lessen the impact of mental illness. Stressful events seem to potentiate its manifestation and yet, there are times it seems to appear spontaneously, much as an uninvited guest.

Mental health has a strong synergistic relationship with physical health, as they are very interdependent and allow us to function at our best only when they are both operating optimally. It should come as no surprise then, that the COVID-19 pandemic contributed to the exponential surge of mental illnesses. Capitalizing on its nondiscriminatory nature, mental illness impacted a large segment of the population – both those suffering from COVID-19 as well as those treating them.

As the nation starts to heal from the immediate and lingering physical and emotional consequences of the COVID-19 pandemic, President Biden has chosen to address and try to meet the needs of the health care heroes, the healers. The signing of H.R. 1667, the Dr. Lorna Breen Health Care Provider Protection Act into law on March 18, 2022, showed dedication to the health care community that has given tirelessly to our nation during the COVID-19 pandemic, and is itself recuperating from that effort.

Taking a top-down approach is essential to assuring the health of the nation. If our healers are not healthy, physically and mentally, they will not be able treat those whom they are dedicated to helping. Openly discussing and acknowledging the mental health problems of health care workers as a community makes it okay to not be okay. It normalizes the need for health care workers to prioritize their own mental health. It can also start to ease the fear of professional backlash or repercussions for practicing self-care.

I, for one, am very grateful for the prioritizing and promoting of the importance of mental health and wellness amongst health care workers. This helps to reduce the stigma of mental illness, helps us understand its impact, and allows us to formulate strategies and solutions to address its effects. The time has come.

Dr. Jarkon is a psychiatrist and director of the Center for Behavioral Health at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y.

Mental illness has been waiting in the wings for years; ignored, ridiculed, minimized, and stigmatized. Those who succumbed to it tried to lend testimonials, but to no avail. Those who were spared its effects remained in disbelief. So, it stayed on the sidelines, growing in intensity and breadth, yet stifled by the masses, until 2 years ago.

In March 2020, when COVID-19 became a pandemic, the importance of mental health finally became undeniable. As the pandemic’s effects progressed and wreaked havoc on our nation, our mental illness rates simultaneously surged. This surge paralleled that of the COVID-19 pandemic’s and in fact, contributed to a secondary crisis, allowing mental health to finally be addressed and gain center stage status.

But “mental health” is not easily defined, as it takes on many forms and is expressed in a variety of ways and via a myriad of symptoms. It does not discriminate by gender, race, age, socioeconomic status, educational level, profession, religion, or geography. At times, mental health status is consistent but at other times it can fluctuate in intensity, duration, and expression. It can be difficult to manage, yet there are various treatment modalities that can be implemented to lessen the impact of mental illness. Stressful events seem to potentiate its manifestation and yet, there are times it seems to appear spontaneously, much as an uninvited guest.

Mental health has a strong synergistic relationship with physical health, as they are very interdependent and allow us to function at our best only when they are both operating optimally. It should come as no surprise then, that the COVID-19 pandemic contributed to the exponential surge of mental illnesses. Capitalizing on its nondiscriminatory nature, mental illness impacted a large segment of the population – both those suffering from COVID-19 as well as those treating them.

As the nation starts to heal from the immediate and lingering physical and emotional consequences of the COVID-19 pandemic, President Biden has chosen to address and try to meet the needs of the health care heroes, the healers. The signing of H.R. 1667, the Dr. Lorna Breen Health Care Provider Protection Act into law on March 18, 2022, showed dedication to the health care community that has given tirelessly to our nation during the COVID-19 pandemic, and is itself recuperating from that effort.

Taking a top-down approach is essential to assuring the health of the nation. If our healers are not healthy, physically and mentally, they will not be able treat those whom they are dedicated to helping. Openly discussing and acknowledging the mental health problems of health care workers as a community makes it okay to not be okay. It normalizes the need for health care workers to prioritize their own mental health. It can also start to ease the fear of professional backlash or repercussions for practicing self-care.

I, for one, am very grateful for the prioritizing and promoting of the importance of mental health and wellness amongst health care workers. This helps to reduce the stigma of mental illness, helps us understand its impact, and allows us to formulate strategies and solutions to address its effects. The time has come.

Dr. Jarkon is a psychiatrist and director of the Center for Behavioral Health at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

A novel blood-based assay could one day be used to diagnose Parkinson’s disease and possibly other chronic inflammatory conditions, according to investigators. In addition to being highly accurate, the assay, which detects changes in expression of cytochrome P450s, is faster and easier to perform than other Parkinson’s disease assays under investigation, reported lead author Kohei Ihara, PhD, of Kobe University, Japan, and colleagues.

“Effective diagnostic systems and biomarkers for patients without subjective motor symptoms have not yet been established,” the investigators wrote in Nature Scientific Reports. “Consequently, the poor diagnostic options for Parkinson’s disease delay the development of therapeutic approaches and medication. Therefore, the development of efficient diagnostic systems and biomarkers is crucial for overcoming Parkinson’s disease.”

According to Dr. Ihara and colleagues, various cytochrome P450 expression patterns and associated serum metabolites correlate with chronic conditions, making them possible markers of disease. To detect these changes, they developed the present assay. It relies upon recombinant P450s expressed on the surface of Escherichia coli. By mixing the E. coli with serum and Vivid, a fluorescent substrate, the investigators can measure “the inhibition rate of the Vivid decomposition reaction” that was driven by “serum metabolites associated with P450s,” revealing underlying expression and, if present, disease.

After some promising initial experiments with mouse models of ulcerative colitis and diabetes, Dr. Ihara and colleagues focused on a rat model of Parkinson’s disease. Evaluating inhibition rates associated with four P450s revealed area-under-the-curve (AUC) values of 0.814-0.914. Two of those P450s were also associated with progression of disease symptoms.

“Therefore, we concluded that the P450 inhibition assay could discriminate between Parkinson’s disease model rats and control rats,” the investigators wrote.

Next, the investigators tested the approach with a case-control study involving 20 patients with Parkinson’s disease and 20 healthy volunteers. Twelve P450s were analyzed, three of which revealed significant differences between patients with Parkinson’s disease and controls, with AUCs ranging from 0.740-0.775. Each of the three P450 enzymes also correlated significantly with stage of disease on the Hoehn & Yahr scale, although severity and frequency of symptoms were not reported.

To increase accuracy of the technique, the investigators developed a logistic regression model using two of the three P450s, generating an AUC of 0.910. Further testing showed that the P450 inhibition assay could distinguish between patients with Parkinson’s disease and Alzheimer’s disease, as well as other chronic inflammatory diseases.

“The P450 inhibition assay is easier to perform and is faster than other assays because this assay does not require pretreatment, such as purification of exosomes, and it involves a single enzymatic reaction,” the investigators wrote, suggesting that the assay may be suitable for real-world diagnosis.
 

‘Promising’ findings need replication

According to Douglas Galasko, MD, a neurologist and professor of neurosciences at UC San Diego Health, the reported accuracy of the assay “seems spectacular,” and the findings are “promising,” but they need to be replicated, “particularly in early-stage patients where the diagnosis [of Parkinson’s disease] is more difficult and important to make.” In practice, the assay would likely see greatest usage for “early diagnosis or diagnosis of unusual or challenging cases,” so accuracy testing needs to be conducted in this setting, he said.

Dr. Galasko, who was not involved in the study, predicted that liquid biopsy for detecting Parkinson’s disease is unlikely to hit the clinic floor anytime soon. “We’re not really close with blood-based biomarkers for Parkinson’s disease,” he said, “unlike the situation for Alzheimer’s disease, where there are several promising blood-based biomarkers.”

For diagnosing Parkinson’s disease, Dr. Galasko suggested that assays using skin biopsies to measure alpha-synuclein accumulation may be closer to approval.

The study was supported by JSPS KAKENHI Grant Number 20K20223 and the Sumitomo Electric Industries Group Corporate Social Responsibility Foundation. The investigators disclosed no conflicts of interest.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

NEW ORLEANS – High out-of-pocket costs for medications used by patients with diabetes are tied to reduced use of these drugs and ultimately worse clinical outcomes, according to findings from two separate studies.

One study looked at the insurance records of more than 70,000 U.S. patients with type 2 diabetes and established cardiovascular disease who were already on metformin. The findings showed that, after adjustment for confounders, the quartile of patients with the highest out-of-pocket cost for an agent from the sodium-glucose cotransporter 2 (SGLT2)–inhibitor class filled a prescription for one of these drugs a significant 21% less often than did patients from the quartile with the lowest personal expense, after adjustment for a variety of potential confounding factors, reported Jing Luo, MD, at the annual scientific sessions of the American Diabetes Association.

A similar analysis run by Dr. Luo and his associates looking at glucagonlike peptide-1 (GLP-1) receptor agonists showed that the quartile of patients who had to pay the most for one of those drugs had an adjusted 12% lower rate of filling a prescription, compared with those with the lowest out-of-pocket expense, a difference that fell just short of significance.

“If we consistently see that high drug costs affect use of highly effective medications in patients with type 2 diabetes and risk factors, it’s quite problematic because it’s not just a matter of money, but it also makes a difference in the patient’s quality of care,” Dr. Luo said in an interview.

Prevention drug lists can help

Consistency turned up in a second report at the same ADA session that retrospectively reviewed data collected during 2004-2017 by a single large U.S. health insurer to identify 3,315 matched pairs of children and adults with diabetes who all had high-deductible health plans for their medical insurance, along with an associated health savings account.

One set of patients in each matched pair began to receive, at some point during follow-up, coverage with a prevention drug list (PDL; also called a formulary) that provided them with a variety of specified agents at no charge. They included oral antidiabetes agents, insulin, antihypertensives, and lipid-lowering drugs. The other half of the matched pairs of patients received no PDL coverage and had copays for their antidiabetes medications.

The findings showed that the rates of out-of-pocket costs for antidiabetes drugs, antidiabetic medications used, and acute diabetes complications all tracked extremely closely between the matched pairs before half of them started to receive their PDL coverage. However, after PDL coverage kicked in, out of pocket costs dropped by 32% for the people with PDL coverage, compared with those who did not receive this coverage. Oral antidiabetes medication use rose modestly, but acute diabetes complications “declined substantially,” with a 14% relative reduction overall in those with PDL coverage, compared with those without, reported J. Franklin Wharam, MBBCh, a professor and health policy researcher at Duke University in Durham, N.C. In the roughly half of the study cohort who fell into a low-income category based on where they lived, the rate of excess acute diabetes complications was 23% higher for those without a PDL, compared with those who had that coverage.

PDL coverage linked with “large reductions in acute, preventable diabetes complications,” concluded Dr. Wharam. “Policy makers and employers should incentivize PDL uptake among low-income patients with diabetes.”

Newer, more effective drugs cost a lot

“The more comorbidities that patients have, the greater is the strength of the evidence for using newer antidiabetes drugs that are more expensive,” but that would mean spending much more on this part of patient care, noted Dr. Luo, an internal medicine physician and researcher at the University of Pittsburgh. “It will cost a lot of money, and I’m not sure what the solution is. It’s a huge conundrum.”

About 30 million Americans have type 2 diabetes. If every one of them went on an SGLT2 inhibitor, or went on an SGLT2 inhibitor plus a GLP-1 receptor agonist, “it would bankrupt the U.S. health care system, so we can’t do that,” commented Sylvio E. Inzucchi, MD, in an interview. “The only thing holding this back is cost. We target these drugs to the patients most apt to benefit from them. If they were generic they would be used much more widely,” noted Dr. Inzucchi, professor and clinical chief of endocrinology at Yale University in New Haven, Conn.

The study run by Dr. Luo and his associates retrospectively reviewed data from 72,743 U.S. adults included in the Optum Clinformatics database during December 2017–December 2019. All included patients had type 2 diabetes, received metformin monotherapy, and had established atherosclerotic cardiovascular disease. They averaged 72 years of age, 56% were men, and 88% were on a Medicare Advantage plan, while the remainder had commercial insurance. Their average hemoglobin A1c level was 6.8%.

People in the quartile with the lowest copays spent an average of about $20/month for either an SGLT2 inhibitor or a GLP-1 receptor agonist. Those in the quartile with the highest copays spent roughly $100/month for agents from each of these two classes. The analysis followed patients for a median of 914 days.

In addition to finding disparate rates of drug use between these two quartiles, the analysis also showed that higher copays linked with longer times to initially fill prescriptions for these drugs. But while those with higher copays took longer to start both classes than did those with the smallest copays, even those with the lowest out-of-pocket costs averaged about a year to initiate treatment.

Dr. Luo attributed this delay to other factors besides costs to patients, such as clinicians prescribing other classes of second-line oral antidiabetes agents, clinical inertia, and lack of awareness by clinicians of the special benefits of SGLT2 inhibitors and GLP-1 receptor antagonists for patients with type 2 diabetes and cardiovascular disease.

“A lot of clinical and social factors drive medication use,” not just out-of-pocket cost, he explained.

Dr. Luo is a consultant to Alosa Health. Dr. Wharam had no disclosures. Dr. Inzucchi is an adviser to Abbott Diagnostics, Esperion Therapeutics, and vTv Therapeutics, a consultant to Merck and Pfizer, and has other relationships with AstraZeneca, Boehringer Ingelheim, Lexicon, and Novo Nordisk.

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

A new study provides more evidence that the substantial weight loss achieved with bariatric surgery offers long-term protection against cancer.

The study found that adults with obesity who had bariatric surgery had a 32% lower risk of developing cancer and a 48% lower risk of dying from cancer, compared with peers who did not have the surgery.

“The magnitude of the benefit was very large and dose-dependent, with more weight loss associated with greater reduction in cancer risk,” lead investigator Ali Aminian, MD, director of the Bariatric & Metabolic Institute, Cleveland Clinic, told this news organization.

The study was published online in the Journal of the American Medical Association.
 

Best evidence to date

“We know that obesity is strongly linked with different types of cancers, but we didn’t know if losing a significant amount of weight can significantly decrease the risk of cancer,” Dr. Aminian explained.

The SPLENDID study involved 30,318 adults with obesity (median age, 46 years; 77% women; median body mass index, 45 kg/m²). 

The 5,053 patients who underwent Roux-en-Y gastric bypass (66%) or sleeve gastrectomy (34%) were matched (1:5) to 25,265 patients who did not undergo bariatric surgery (nonsurgical control group).

At 10 years, patients who had bariatric surgery had lost 27.5 kg (60 pounds) compared with 2.7 kg (6 pounds) for peers who didn’t have the surgery, a difference of 19.2%. 

During a median follow-up of 6.1 years, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-associated cancer (incidence rate of 3.0 vs. 4.6 events per 1,000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower in the bariatric surgery group (2.9% vs. 4.9%; absolute risk difference, 2.0%; 95% confidence interval [CI], 1.2%-2.7%; adjusted hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P = .002).

Most cancer types were less common in the bariatric surgery group. However, a comprehensive analysis of the impact of bariatric surgery on individual cancer types was not possible.

In the fully-adjusted Cox models, the association between bariatric surgery and individual cancer types was significant only for endometrial cancer (adjusted HR, 0.47; 95% CI, 0.27-0.83). 

For the other individual cancers, there was a “trend or signal toward a reduction in their risk after the surgery,” Dr. Aminian said.

He noted that endometrial cancer has the strongest association with obesity, and patients who seek bariatric surgery are typically obese, middle-aged women.

“So, it was not surprising that we had more cases of endometrial cancer than other types of cancer,” he said.

The SPLENDID study also showed a significant reduction in cancer-related mortality at 10 years in patients with vs. without bariatric surgery (0.8% vs. 1.4%; adjusted HR, 0.52; 95% CI, 0.31-0.88; P = .01).

The benefits of bariatric surgery were evident in both women and men, younger and older patients, and Black and White patients, and were similarly observed after both gastric bypass and sleeve gastrectomy.

For the cancer protective effect, patients need to lose at least 20%-25% of their body weight, which is almost impossible with diet alone, Dr. Aminian said.

Obesity is “second only to tobacco” as a preventable cause of cancer in the United States, senior author Steven Nissen, MD, chief academic officer of the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, said in a news release.

“This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality,” Dr. Nissen said.
 

Questions remain

In an accompanying editorial, Anita P. Courcoulas, MD, of the University of Pittsburgh Medical Center, said future studies should look at potential factors that influence the association between bariatric surgery and reduced cancer risk, with an eye toward individualizing treatment and figuring out who will benefit the most.

“It is likely that cancer risk reduction after bariatric surgery varies by sex, age, race and ethnicity, type of bariatric surgery, alcohol and smoking status, cancer site, diabetes status, body mass index, and other factors,” Dr. Courcoulas pointed out.

“In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans,” she said.

“If this association is further validated, it would extend the benefits of bariatric surgery to another important area of long-term health and prevention. This additional information could then further guide for whom bariatric surgery is most beneficial,” Dr. Courcoulas concluded.

The study had no specific funding. Dr. Aminian reported receiving grants and speaking honoraria from Medtronic. Dr. Nissen reported receiving grants from Novartis, Eli Lilly, AbbVie, Silence Therapeutics, AstraZeneca, Esperion Therapeutics, Amgen, and Bristol Myers Squibb. A complete list of author disclosures is available with the original article.  Dr. Courcoulas had no relevant disclosures.

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

A new study provides more evidence that the substantial weight loss achieved with bariatric surgery offers long-term protection against cancer.

The study found that adults with obesity who had bariatric surgery had a 32% lower risk of developing cancer and a 48% lower risk of dying from cancer, compared with peers who did not have the surgery.

“The magnitude of the benefit was very large and dose-dependent, with more weight loss associated with greater reduction in cancer risk,” lead investigator Ali Aminian, MD, director of the Bariatric & Metabolic Institute, Cleveland Clinic, told this news organization.

The study was published online in the Journal of the American Medical Association.
 

Best evidence to date

“We know that obesity is strongly linked with different types of cancers, but we didn’t know if losing a significant amount of weight can significantly decrease the risk of cancer,” Dr. Aminian explained.

The SPLENDID study involved 30,318 adults with obesity (median age, 46 years; 77% women; median body mass index, 45 kg/m²). 

The 5,053 patients who underwent Roux-en-Y gastric bypass (66%) or sleeve gastrectomy (34%) were matched (1:5) to 25,265 patients who did not undergo bariatric surgery (nonsurgical control group).

At 10 years, patients who had bariatric surgery had lost 27.5 kg (60 pounds) compared with 2.7 kg (6 pounds) for peers who didn’t have the surgery, a difference of 19.2%. 

During a median follow-up of 6.1 years, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-associated cancer (incidence rate of 3.0 vs. 4.6 events per 1,000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower in the bariatric surgery group (2.9% vs. 4.9%; absolute risk difference, 2.0%; 95% confidence interval [CI], 1.2%-2.7%; adjusted hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P = .002).

Most cancer types were less common in the bariatric surgery group. However, a comprehensive analysis of the impact of bariatric surgery on individual cancer types was not possible.

In the fully-adjusted Cox models, the association between bariatric surgery and individual cancer types was significant only for endometrial cancer (adjusted HR, 0.47; 95% CI, 0.27-0.83). 

For the other individual cancers, there was a “trend or signal toward a reduction in their risk after the surgery,” Dr. Aminian said.

He noted that endometrial cancer has the strongest association with obesity, and patients who seek bariatric surgery are typically obese, middle-aged women.

“So, it was not surprising that we had more cases of endometrial cancer than other types of cancer,” he said.

The SPLENDID study also showed a significant reduction in cancer-related mortality at 10 years in patients with vs. without bariatric surgery (0.8% vs. 1.4%; adjusted HR, 0.52; 95% CI, 0.31-0.88; P = .01).

The benefits of bariatric surgery were evident in both women and men, younger and older patients, and Black and White patients, and were similarly observed after both gastric bypass and sleeve gastrectomy.

For the cancer protective effect, patients need to lose at least 20%-25% of their body weight, which is almost impossible with diet alone, Dr. Aminian said.

Obesity is “second only to tobacco” as a preventable cause of cancer in the United States, senior author Steven Nissen, MD, chief academic officer of the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, said in a news release.

“This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality,” Dr. Nissen said.
 

Questions remain

In an accompanying editorial, Anita P. Courcoulas, MD, of the University of Pittsburgh Medical Center, said future studies should look at potential factors that influence the association between bariatric surgery and reduced cancer risk, with an eye toward individualizing treatment and figuring out who will benefit the most.

“It is likely that cancer risk reduction after bariatric surgery varies by sex, age, race and ethnicity, type of bariatric surgery, alcohol and smoking status, cancer site, diabetes status, body mass index, and other factors,” Dr. Courcoulas pointed out.

“In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans,” she said.

“If this association is further validated, it would extend the benefits of bariatric surgery to another important area of long-term health and prevention. This additional information could then further guide for whom bariatric surgery is most beneficial,” Dr. Courcoulas concluded.

The study had no specific funding. Dr. Aminian reported receiving grants and speaking honoraria from Medtronic. Dr. Nissen reported receiving grants from Novartis, Eli Lilly, AbbVie, Silence Therapeutics, AstraZeneca, Esperion Therapeutics, Amgen, and Bristol Myers Squibb. A complete list of author disclosures is available with the original article.  Dr. Courcoulas had no relevant disclosures.

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

A new study provides more evidence that the substantial weight loss achieved with bariatric surgery offers long-term protection against cancer.

The study found that adults with obesity who had bariatric surgery had a 32% lower risk of developing cancer and a 48% lower risk of dying from cancer, compared with peers who did not have the surgery.

“The magnitude of the benefit was very large and dose-dependent, with more weight loss associated with greater reduction in cancer risk,” lead investigator Ali Aminian, MD, director of the Bariatric & Metabolic Institute, Cleveland Clinic, told this news organization.

The study was published online in the Journal of the American Medical Association.
 

Best evidence to date

“We know that obesity is strongly linked with different types of cancers, but we didn’t know if losing a significant amount of weight can significantly decrease the risk of cancer,” Dr. Aminian explained.

The SPLENDID study involved 30,318 adults with obesity (median age, 46 years; 77% women; median body mass index, 45 kg/m²). 

The 5,053 patients who underwent Roux-en-Y gastric bypass (66%) or sleeve gastrectomy (34%) were matched (1:5) to 25,265 patients who did not undergo bariatric surgery (nonsurgical control group).

At 10 years, patients who had bariatric surgery had lost 27.5 kg (60 pounds) compared with 2.7 kg (6 pounds) for peers who didn’t have the surgery, a difference of 19.2%. 

During a median follow-up of 6.1 years, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-associated cancer (incidence rate of 3.0 vs. 4.6 events per 1,000 person-years).

At 10 years, the cumulative incidence of obesity-associated cancer was significantly lower in the bariatric surgery group (2.9% vs. 4.9%; absolute risk difference, 2.0%; 95% confidence interval [CI], 1.2%-2.7%; adjusted hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P = .002).

Most cancer types were less common in the bariatric surgery group. However, a comprehensive analysis of the impact of bariatric surgery on individual cancer types was not possible.

In the fully-adjusted Cox models, the association between bariatric surgery and individual cancer types was significant only for endometrial cancer (adjusted HR, 0.47; 95% CI, 0.27-0.83). 

For the other individual cancers, there was a “trend or signal toward a reduction in their risk after the surgery,” Dr. Aminian said.

He noted that endometrial cancer has the strongest association with obesity, and patients who seek bariatric surgery are typically obese, middle-aged women.

“So, it was not surprising that we had more cases of endometrial cancer than other types of cancer,” he said.

The SPLENDID study also showed a significant reduction in cancer-related mortality at 10 years in patients with vs. without bariatric surgery (0.8% vs. 1.4%; adjusted HR, 0.52; 95% CI, 0.31-0.88; P = .01).

The benefits of bariatric surgery were evident in both women and men, younger and older patients, and Black and White patients, and were similarly observed after both gastric bypass and sleeve gastrectomy.

For the cancer protective effect, patients need to lose at least 20%-25% of their body weight, which is almost impossible with diet alone, Dr. Aminian said.

Obesity is “second only to tobacco” as a preventable cause of cancer in the United States, senior author Steven Nissen, MD, chief academic officer of the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, said in a news release.

“This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality,” Dr. Nissen said.
 

Questions remain

In an accompanying editorial, Anita P. Courcoulas, MD, of the University of Pittsburgh Medical Center, said future studies should look at potential factors that influence the association between bariatric surgery and reduced cancer risk, with an eye toward individualizing treatment and figuring out who will benefit the most.

“It is likely that cancer risk reduction after bariatric surgery varies by sex, age, race and ethnicity, type of bariatric surgery, alcohol and smoking status, cancer site, diabetes status, body mass index, and other factors,” Dr. Courcoulas pointed out.

“In addition, there is a need to understand the specific biological mechanisms of effect responsible for the observed change in cancer risk because these mechanisms have not been clearly investigated and elucidated in humans,” she said.

“If this association is further validated, it would extend the benefits of bariatric surgery to another important area of long-term health and prevention. This additional information could then further guide for whom bariatric surgery is most beneficial,” Dr. Courcoulas concluded.

The study had no specific funding. Dr. Aminian reported receiving grants and speaking honoraria from Medtronic. Dr. Nissen reported receiving grants from Novartis, Eli Lilly, AbbVie, Silence Therapeutics, AstraZeneca, Esperion Therapeutics, Amgen, and Bristol Myers Squibb. A complete list of author disclosures is available with the original article.  Dr. Courcoulas had no relevant disclosures.

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

Kendra Joseph of San Antonio, Tex., had given up on the idea of having a second child. At 40 years old, and with a daughter pleading for a sibling, she and her husband were nervous about the risk of trying for another child due to her advanced maternal age. Mrs. Joseph had ended an earlier pregnancy at 15 weeks after finding out her son had Edwards syndrome, a genetic trait that’s fatal in most cases.

Now a new Texas law that bans abortion past 6 weeks would mean that if either she or her baby were at risk of dying, she might still have to carry the baby to term. For Mrs. Joseph, it wasn’t worth the risk at first. Then in February, just as they had decided against another baby, the couple found out they were expecting. She’s thrilled about her pregnancy, but it’s also been a nervewracking few months.

“It’s scary being pregnant anyway,” she says, “but these new restrictions add a layer of stress.”

Twenty-eight states could ban or tightly restrict abortion if the Supreme Court overturns the landmark Roe v. Wade decision. A leaked draft of the court’s opinion has been widely interpreted as signaling that the court will overturn the law. This means that women who are at a higher risk of pregnancy complications or those who have chronic conditions before getting pregnant could be at risk of dying if they can’t get an abortion.

According to the CDC, the maternal mortality rate in the United States in 2020 was 23.8 deaths per 100,000 live births – among the highest in the developed world. The rate is eight times as high as it is in countries like the Netherlands, Norway, and New Zealand.

“Many of the women I take care of have a pregnancy that presents a real and present danger to their health, and this often goes along with the fact that they’re very unlikely to have a healthy baby,” says Chavi Karkowsky, MD, a maternal fetal medicine specialist at Montefiore Medical Center, New York.

Maternal mortality, she says, can be caused by health conditions that some women may not know about before getting pregnant. (For example, finding out she had cervical cancer at a prenatal visit and then having to choose between chemotherapy and her baby.) And there are also life-threatening conditions caused by pregnancy, like preeclampsia, which can cause high blood pressure and kidney damage, as well as gestational diabetes. Research has also shown that the risk of maternal mortality increases with age.

University of Colorado researchers, in a study published in the journal Demography, found that banning abortion nationwide would lead to a 20% increase in maternal death. For Black women, the increase in mortality could be as high as 33%, due to higher rates of poverty and less access to health care, says Amanda Stevenson, PhD, a sociologist at the University of Colorado and one of the study’s authors. Black women in the U.S. are more than three times as likely to die as a result of pregnancy complications due to poor exposure to health care, structural racism, and chronic health conditions, according to the CDC.

If Roe v. Wade is overturned, more women will likely die because remaining pregnant poses a far greater mortality risk for them than the risk associated with an abortion, says Dr. Stevenson.

For women with high-risk pregnancies who need an abortion, traveling out of state puts them at a health risk, says Jamila Perritt, MD, an ob.gyn. in Washington, D.C. and president of Physicians for Reproductive Health. In places where abortion is restricted, it can cause significant delays in accessing medical care. “Abortion is a time-sensitive procedure, and as the pregnancy progresses, it can become increasingly difficult to find a clinic that will provide care,” she says.

She recalls one of her patients who had a heart problem that required a pregnancy to be ended. The patient at first had to travel to find a doctor who could evaluate her unique condition, then go out of state to get an abortion. All the while, the clock was ticking and her health was at risk. In this case, the patient had the money to travel out of state, find child care, and pay for the procedure.

“This was a resourced individual, and while this was difficult for her, it wasn’t impossible,” says Dr. Perritt.

Many of the states with the highest maternal mortality rates, including Louisiana, Texas, Arkansas, Alabama, South Carolina, and Georgia, also plan to strictly limit abortions or ban them completely. Some abortion opponents insist this won’t harm mothers.

“The pro-life movement loves both babies and moms,” says Sarah Zagorski, a spokeswoman for Louisiana Right to Life. “It is a tragedy that Louisiana has high mortality rates among pregnant women. However, legal abortion does not improve these rates.”

But for many women who need an abortion, statewide bans may make it hard to get. This worries Kendra Joseph, who’s now 18 weeks into her pregnancy.

“I try to put the bad things that could happen out of my mind, but it’s really hard when you’re dealing with these totally unnecessary and cruel restrictions. We as women, we’re just losing so much,” she says.

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

Kendra Joseph of San Antonio, Tex., had given up on the idea of having a second child. At 40 years old, and with a daughter pleading for a sibling, she and her husband were nervous about the risk of trying for another child due to her advanced maternal age. Mrs. Joseph had ended an earlier pregnancy at 15 weeks after finding out her son had Edwards syndrome, a genetic trait that’s fatal in most cases.

Now a new Texas law that bans abortion past 6 weeks would mean that if either she or her baby were at risk of dying, she might still have to carry the baby to term. For Mrs. Joseph, it wasn’t worth the risk at first. Then in February, just as they had decided against another baby, the couple found out they were expecting. She’s thrilled about her pregnancy, but it’s also been a nervewracking few months.

“It’s scary being pregnant anyway,” she says, “but these new restrictions add a layer of stress.”

Twenty-eight states could ban or tightly restrict abortion if the Supreme Court overturns the landmark Roe v. Wade decision. A leaked draft of the court’s opinion has been widely interpreted as signaling that the court will overturn the law. This means that women who are at a higher risk of pregnancy complications or those who have chronic conditions before getting pregnant could be at risk of dying if they can’t get an abortion.

According to the CDC, the maternal mortality rate in the United States in 2020 was 23.8 deaths per 100,000 live births – among the highest in the developed world. The rate is eight times as high as it is in countries like the Netherlands, Norway, and New Zealand.

“Many of the women I take care of have a pregnancy that presents a real and present danger to their health, and this often goes along with the fact that they’re very unlikely to have a healthy baby,” says Chavi Karkowsky, MD, a maternal fetal medicine specialist at Montefiore Medical Center, New York.

Maternal mortality, she says, can be caused by health conditions that some women may not know about before getting pregnant. (For example, finding out she had cervical cancer at a prenatal visit and then having to choose between chemotherapy and her baby.) And there are also life-threatening conditions caused by pregnancy, like preeclampsia, which can cause high blood pressure and kidney damage, as well as gestational diabetes. Research has also shown that the risk of maternal mortality increases with age.

University of Colorado researchers, in a study published in the journal Demography, found that banning abortion nationwide would lead to a 20% increase in maternal death. For Black women, the increase in mortality could be as high as 33%, due to higher rates of poverty and less access to health care, says Amanda Stevenson, PhD, a sociologist at the University of Colorado and one of the study’s authors. Black women in the U.S. are more than three times as likely to die as a result of pregnancy complications due to poor exposure to health care, structural racism, and chronic health conditions, according to the CDC.

If Roe v. Wade is overturned, more women will likely die because remaining pregnant poses a far greater mortality risk for them than the risk associated with an abortion, says Dr. Stevenson.

For women with high-risk pregnancies who need an abortion, traveling out of state puts them at a health risk, says Jamila Perritt, MD, an ob.gyn. in Washington, D.C. and president of Physicians for Reproductive Health. In places where abortion is restricted, it can cause significant delays in accessing medical care. “Abortion is a time-sensitive procedure, and as the pregnancy progresses, it can become increasingly difficult to find a clinic that will provide care,” she says.

She recalls one of her patients who had a heart problem that required a pregnancy to be ended. The patient at first had to travel to find a doctor who could evaluate her unique condition, then go out of state to get an abortion. All the while, the clock was ticking and her health was at risk. In this case, the patient had the money to travel out of state, find child care, and pay for the procedure.

“This was a resourced individual, and while this was difficult for her, it wasn’t impossible,” says Dr. Perritt.

Many of the states with the highest maternal mortality rates, including Louisiana, Texas, Arkansas, Alabama, South Carolina, and Georgia, also plan to strictly limit abortions or ban them completely. Some abortion opponents insist this won’t harm mothers.

“The pro-life movement loves both babies and moms,” says Sarah Zagorski, a spokeswoman for Louisiana Right to Life. “It is a tragedy that Louisiana has high mortality rates among pregnant women. However, legal abortion does not improve these rates.”

But for many women who need an abortion, statewide bans may make it hard to get. This worries Kendra Joseph, who’s now 18 weeks into her pregnancy.

“I try to put the bad things that could happen out of my mind, but it’s really hard when you’re dealing with these totally unnecessary and cruel restrictions. We as women, we’re just losing so much,” she says.

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

Kendra Joseph of San Antonio, Tex., had given up on the idea of having a second child. At 40 years old, and with a daughter pleading for a sibling, she and her husband were nervous about the risk of trying for another child due to her advanced maternal age. Mrs. Joseph had ended an earlier pregnancy at 15 weeks after finding out her son had Edwards syndrome, a genetic trait that’s fatal in most cases.

Now a new Texas law that bans abortion past 6 weeks would mean that if either she or her baby were at risk of dying, she might still have to carry the baby to term. For Mrs. Joseph, it wasn’t worth the risk at first. Then in February, just as they had decided against another baby, the couple found out they were expecting. She’s thrilled about her pregnancy, but it’s also been a nervewracking few months.

“It’s scary being pregnant anyway,” she says, “but these new restrictions add a layer of stress.”

Twenty-eight states could ban or tightly restrict abortion if the Supreme Court overturns the landmark Roe v. Wade decision. A leaked draft of the court’s opinion has been widely interpreted as signaling that the court will overturn the law. This means that women who are at a higher risk of pregnancy complications or those who have chronic conditions before getting pregnant could be at risk of dying if they can’t get an abortion.

According to the CDC, the maternal mortality rate in the United States in 2020 was 23.8 deaths per 100,000 live births – among the highest in the developed world. The rate is eight times as high as it is in countries like the Netherlands, Norway, and New Zealand.

“Many of the women I take care of have a pregnancy that presents a real and present danger to their health, and this often goes along with the fact that they’re very unlikely to have a healthy baby,” says Chavi Karkowsky, MD, a maternal fetal medicine specialist at Montefiore Medical Center, New York.

Maternal mortality, she says, can be caused by health conditions that some women may not know about before getting pregnant. (For example, finding out she had cervical cancer at a prenatal visit and then having to choose between chemotherapy and her baby.) And there are also life-threatening conditions caused by pregnancy, like preeclampsia, which can cause high blood pressure and kidney damage, as well as gestational diabetes. Research has also shown that the risk of maternal mortality increases with age.

University of Colorado researchers, in a study published in the journal Demography, found that banning abortion nationwide would lead to a 20% increase in maternal death. For Black women, the increase in mortality could be as high as 33%, due to higher rates of poverty and less access to health care, says Amanda Stevenson, PhD, a sociologist at the University of Colorado and one of the study’s authors. Black women in the U.S. are more than three times as likely to die as a result of pregnancy complications due to poor exposure to health care, structural racism, and chronic health conditions, according to the CDC.

If Roe v. Wade is overturned, more women will likely die because remaining pregnant poses a far greater mortality risk for them than the risk associated with an abortion, says Dr. Stevenson.

For women with high-risk pregnancies who need an abortion, traveling out of state puts them at a health risk, says Jamila Perritt, MD, an ob.gyn. in Washington, D.C. and president of Physicians for Reproductive Health. In places where abortion is restricted, it can cause significant delays in accessing medical care. “Abortion is a time-sensitive procedure, and as the pregnancy progresses, it can become increasingly difficult to find a clinic that will provide care,” she says.

She recalls one of her patients who had a heart problem that required a pregnancy to be ended. The patient at first had to travel to find a doctor who could evaluate her unique condition, then go out of state to get an abortion. All the while, the clock was ticking and her health was at risk. In this case, the patient had the money to travel out of state, find child care, and pay for the procedure.

“This was a resourced individual, and while this was difficult for her, it wasn’t impossible,” says Dr. Perritt.

Many of the states with the highest maternal mortality rates, including Louisiana, Texas, Arkansas, Alabama, South Carolina, and Georgia, also plan to strictly limit abortions or ban them completely. Some abortion opponents insist this won’t harm mothers.

“The pro-life movement loves both babies and moms,” says Sarah Zagorski, a spokeswoman for Louisiana Right to Life. “It is a tragedy that Louisiana has high mortality rates among pregnant women. However, legal abortion does not improve these rates.”

But for many women who need an abortion, statewide bans may make it hard to get. This worries Kendra Joseph, who’s now 18 weeks into her pregnancy.

“I try to put the bad things that could happen out of my mind, but it’s really hard when you’re dealing with these totally unnecessary and cruel restrictions. We as women, we’re just losing so much,” she says.

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

NEW ORLEANS – Obesity in adolescence is linked to an increased risk for type 1 diabetes onset in adulthood, new research suggests.

These new data, from Israeli military recruits followed for over a decade, suggest that obesity may be playing a causal role in type 1 as well as type 2 diabetes.

The incidence of type 1 diabetes has been increasing by about 2%-3% annually over recent decades, but the reasons aren’t clear. The study is the first to examine the role of obesity in adolescence and type 1 diabetes in young adulthood, and also the first to examine the question of using antibody status as part of the criteria for a type 1 diagnosis.

The findings were reported at the annual scientific sessions of the American Diabetes Association by Gilad Twig, MD, PhD, professor of medicine at Sheba Medical Center, Tel HaShomer, Israel. “For people who might have a high risk for developing type 1 diabetes, these results emphasize the importance of maintaining a normal weight,” he said in an interview. He noted that, although this recommendation applies to everyone, “here it’s becoming more precise for the population – more individualized in the sense that this might specifically help you.”

Naveed Sattar, PhD, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, said in an interview that carrying too much weight “will make the pancreas have to work harder to make insulin to keep the sugar normal. So, if you’re stressing the system and the pancreas is already likely to fail, it will fail faster.”

Clinically, Dr. Sattar said, “Lifestyle does matter to the risk of developing type 1 diabetes. The weighting may be different [from type 2]. The major factor in type 1 is still the genetics, but if you have a family history of type 1 and your genetic potential is greater, you will minimize your risk by staying leaner.”
 

Study highlights that type 1 is not always ‘juvenile’

In addition to countering the long-held belief that type 1 diabetes is primarily a condition of thin individuals and unrelated to obesity, the data also reinforce the emerging recognition that type 1 diabetes isn’t always “juvenile” and in fact often arises in adulthood.

“About half of all cases of type 1 diabetes develop after age 18. By reputation, people think it’s a disease of children. But it’s begun to grow so that now 50% of cases occur after late adolescence,” noted Dr. Twig.

Dr. Sattar pointed to a UK Biobank study showing that nearly half of all cases of type 1 diabetes arise after age 30 years. “You absolutely can get type 1 in adulthood. It’s not rare.”
 

Direct correlation seen in otherwise healthy young people

The retrospective nationwide cohort study included 1,426,362 17-year-olds (834,050 male and 592,312 female) who underwent medical evaluation prior to military conscription starting in January 1996 and followed them through 2016. At baseline, none had a history of dysglycemia.

The data were linked with information about adult-onset type 1 diabetes in the Israeli National Diabetes Registry. In all, 777 incident type 1 diabetes cases were recorded over the study period, with a rate of 4.9 cases per 100,000 person-years.

Over a median follow-up of 11.2 years, there was a graded incidence of type 1 diabetes across BMI groups from underweight to obesity, from 3.6 to 8.4 cases per 100,000 person-years.

After adjustment for sex, birth year, age at study entry, education, and cognitive performance with BMI 5th-49th percentiles as the reference, the hazard ratios were 1.05 for the 50th-74th BMI percentiles, 1.41 for 75th-84th, 1.54 for those who were overweight, and 2.05 for those with obesity.

Every 5-unit increment in BMI corresponded to a 35% greater incidence of type 1 diabetes (adjusted hazard ratio 1.35) and every one increment was associated with a 35% greater risk (1.25), both values significant.

Sensitivity analyses resulted in similar findings for those with no other chronic health conditions at baseline. The results also didn’t change in a separate analysis of 574,720 subjects in whom autoantibody data were available to confirm the type 1 diabetes diagnosis.
 

Hypotheses for mechanisms

The mechanism for the association isn’t clear, but in a simultaneously published article in Diabetologia, Dr. Twig and colleagues outline several hypotheses. One relates to the growing evidence of a link between various autoimmune conditions, which point to the possibility of elevated adipokines and cytokines in obesity diminishing self-tolerance by promoting proinflammatory processes.

The authors cite data from the TrialNet Pathway to Prevention study of relatives of people with type 1 diabetes in which participants who were overweight and obese had an increased risk of islet autoantibody expression. However, not all data have supported this finding.

“Obesity is related to several other autoimmune conditions, so it’s not a complete surprise it might be related to another,” Dr. Twig noted.

Other possibilities include vitamin D deficiency, a high-fat diet, and alterations in gut microbiota.

And then there’s the “accelerator hypothesis,” suggesting that both type 1 and type 2 diabetes result from insulin resistance and genetic background that affect the rate of beta cell loss and the disease phenotype. Dr. Sattar said that the accelerator hypotheses “makes complete sense to me. Because the population is so obese, we’re seeing it more now whereas we might not have seen it 40 years ago when the BMI differentials were far less in society.”

Dr. Twig has no disclosures. Dr. Sattar has consulted for or received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution.

NEW ORLEANS – Obesity in adolescence is linked to an increased risk for type 1 diabetes onset in adulthood, new research suggests.

These new data, from Israeli military recruits followed for over a decade, suggest that obesity may be playing a causal role in type 1 as well as type 2 diabetes.

The incidence of type 1 diabetes has been increasing by about 2%-3% annually over recent decades, but the reasons aren’t clear. The study is the first to examine the role of obesity in adolescence and type 1 diabetes in young adulthood, and also the first to examine the question of using antibody status as part of the criteria for a type 1 diagnosis.

The findings were reported at the annual scientific sessions of the American Diabetes Association by Gilad Twig, MD, PhD, professor of medicine at Sheba Medical Center, Tel HaShomer, Israel. “For people who might have a high risk for developing type 1 diabetes, these results emphasize the importance of maintaining a normal weight,” he said in an interview. He noted that, although this recommendation applies to everyone, “here it’s becoming more precise for the population – more individualized in the sense that this might specifically help you.”

Naveed Sattar, PhD, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, said in an interview that carrying too much weight “will make the pancreas have to work harder to make insulin to keep the sugar normal. So, if you’re stressing the system and the pancreas is already likely to fail, it will fail faster.”

Clinically, Dr. Sattar said, “Lifestyle does matter to the risk of developing type 1 diabetes. The weighting may be different [from type 2]. The major factor in type 1 is still the genetics, but if you have a family history of type 1 and your genetic potential is greater, you will minimize your risk by staying leaner.”
 

Study highlights that type 1 is not always ‘juvenile’

In addition to countering the long-held belief that type 1 diabetes is primarily a condition of thin individuals and unrelated to obesity, the data also reinforce the emerging recognition that type 1 diabetes isn’t always “juvenile” and in fact often arises in adulthood.

“About half of all cases of type 1 diabetes develop after age 18. By reputation, people think it’s a disease of children. But it’s begun to grow so that now 50% of cases occur after late adolescence,” noted Dr. Twig.

Dr. Sattar pointed to a UK Biobank study showing that nearly half of all cases of type 1 diabetes arise after age 30 years. “You absolutely can get type 1 in adulthood. It’s not rare.”
 

Direct correlation seen in otherwise healthy young people

The retrospective nationwide cohort study included 1,426,362 17-year-olds (834,050 male and 592,312 female) who underwent medical evaluation prior to military conscription starting in January 1996 and followed them through 2016. At baseline, none had a history of dysglycemia.

The data were linked with information about adult-onset type 1 diabetes in the Israeli National Diabetes Registry. In all, 777 incident type 1 diabetes cases were recorded over the study period, with a rate of 4.9 cases per 100,000 person-years.

Over a median follow-up of 11.2 years, there was a graded incidence of type 1 diabetes across BMI groups from underweight to obesity, from 3.6 to 8.4 cases per 100,000 person-years.

After adjustment for sex, birth year, age at study entry, education, and cognitive performance with BMI 5th-49th percentiles as the reference, the hazard ratios were 1.05 for the 50th-74th BMI percentiles, 1.41 for 75th-84th, 1.54 for those who were overweight, and 2.05 for those with obesity.

Every 5-unit increment in BMI corresponded to a 35% greater incidence of type 1 diabetes (adjusted hazard ratio 1.35) and every one increment was associated with a 35% greater risk (1.25), both values significant.

Sensitivity analyses resulted in similar findings for those with no other chronic health conditions at baseline. The results also didn’t change in a separate analysis of 574,720 subjects in whom autoantibody data were available to confirm the type 1 diabetes diagnosis.
 

Hypotheses for mechanisms

The mechanism for the association isn’t clear, but in a simultaneously published article in Diabetologia, Dr. Twig and colleagues outline several hypotheses. One relates to the growing evidence of a link between various autoimmune conditions, which point to the possibility of elevated adipokines and cytokines in obesity diminishing self-tolerance by promoting proinflammatory processes.

The authors cite data from the TrialNet Pathway to Prevention study of relatives of people with type 1 diabetes in which participants who were overweight and obese had an increased risk of islet autoantibody expression. However, not all data have supported this finding.

“Obesity is related to several other autoimmune conditions, so it’s not a complete surprise it might be related to another,” Dr. Twig noted.

Other possibilities include vitamin D deficiency, a high-fat diet, and alterations in gut microbiota.

And then there’s the “accelerator hypothesis,” suggesting that both type 1 and type 2 diabetes result from insulin resistance and genetic background that affect the rate of beta cell loss and the disease phenotype. Dr. Sattar said that the accelerator hypotheses “makes complete sense to me. Because the population is so obese, we’re seeing it more now whereas we might not have seen it 40 years ago when the BMI differentials were far less in society.”

Dr. Twig has no disclosures. Dr. Sattar has consulted for or received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution.

NEW ORLEANS – Obesity in adolescence is linked to an increased risk for type 1 diabetes onset in adulthood, new research suggests.

These new data, from Israeli military recruits followed for over a decade, suggest that obesity may be playing a causal role in type 1 as well as type 2 diabetes.

The incidence of type 1 diabetes has been increasing by about 2%-3% annually over recent decades, but the reasons aren’t clear. The study is the first to examine the role of obesity in adolescence and type 1 diabetes in young adulthood, and also the first to examine the question of using antibody status as part of the criteria for a type 1 diagnosis.

The findings were reported at the annual scientific sessions of the American Diabetes Association by Gilad Twig, MD, PhD, professor of medicine at Sheba Medical Center, Tel HaShomer, Israel. “For people who might have a high risk for developing type 1 diabetes, these results emphasize the importance of maintaining a normal weight,” he said in an interview. He noted that, although this recommendation applies to everyone, “here it’s becoming more precise for the population – more individualized in the sense that this might specifically help you.”

Naveed Sattar, PhD, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, said in an interview that carrying too much weight “will make the pancreas have to work harder to make insulin to keep the sugar normal. So, if you’re stressing the system and the pancreas is already likely to fail, it will fail faster.”

Clinically, Dr. Sattar said, “Lifestyle does matter to the risk of developing type 1 diabetes. The weighting may be different [from type 2]. The major factor in type 1 is still the genetics, but if you have a family history of type 1 and your genetic potential is greater, you will minimize your risk by staying leaner.”
 

Study highlights that type 1 is not always ‘juvenile’

In addition to countering the long-held belief that type 1 diabetes is primarily a condition of thin individuals and unrelated to obesity, the data also reinforce the emerging recognition that type 1 diabetes isn’t always “juvenile” and in fact often arises in adulthood.

“About half of all cases of type 1 diabetes develop after age 18. By reputation, people think it’s a disease of children. But it’s begun to grow so that now 50% of cases occur after late adolescence,” noted Dr. Twig.

Dr. Sattar pointed to a UK Biobank study showing that nearly half of all cases of type 1 diabetes arise after age 30 years. “You absolutely can get type 1 in adulthood. It’s not rare.”
 

Direct correlation seen in otherwise healthy young people

The retrospective nationwide cohort study included 1,426,362 17-year-olds (834,050 male and 592,312 female) who underwent medical evaluation prior to military conscription starting in January 1996 and followed them through 2016. At baseline, none had a history of dysglycemia.

The data were linked with information about adult-onset type 1 diabetes in the Israeli National Diabetes Registry. In all, 777 incident type 1 diabetes cases were recorded over the study period, with a rate of 4.9 cases per 100,000 person-years.

Over a median follow-up of 11.2 years, there was a graded incidence of type 1 diabetes across BMI groups from underweight to obesity, from 3.6 to 8.4 cases per 100,000 person-years.

After adjustment for sex, birth year, age at study entry, education, and cognitive performance with BMI 5th-49th percentiles as the reference, the hazard ratios were 1.05 for the 50th-74th BMI percentiles, 1.41 for 75th-84th, 1.54 for those who were overweight, and 2.05 for those with obesity.

Every 5-unit increment in BMI corresponded to a 35% greater incidence of type 1 diabetes (adjusted hazard ratio 1.35) and every one increment was associated with a 35% greater risk (1.25), both values significant.

Sensitivity analyses resulted in similar findings for those with no other chronic health conditions at baseline. The results also didn’t change in a separate analysis of 574,720 subjects in whom autoantibody data were available to confirm the type 1 diabetes diagnosis.
 

Hypotheses for mechanisms

The mechanism for the association isn’t clear, but in a simultaneously published article in Diabetologia, Dr. Twig and colleagues outline several hypotheses. One relates to the growing evidence of a link between various autoimmune conditions, which point to the possibility of elevated adipokines and cytokines in obesity diminishing self-tolerance by promoting proinflammatory processes.

The authors cite data from the TrialNet Pathway to Prevention study of relatives of people with type 1 diabetes in which participants who were overweight and obese had an increased risk of islet autoantibody expression. However, not all data have supported this finding.

“Obesity is related to several other autoimmune conditions, so it’s not a complete surprise it might be related to another,” Dr. Twig noted.

Other possibilities include vitamin D deficiency, a high-fat diet, and alterations in gut microbiota.

And then there’s the “accelerator hypothesis,” suggesting that both type 1 and type 2 diabetes result from insulin resistance and genetic background that affect the rate of beta cell loss and the disease phenotype. Dr. Sattar said that the accelerator hypotheses “makes complete sense to me. Because the population is so obese, we’re seeing it more now whereas we might not have seen it 40 years ago when the BMI differentials were far less in society.”

Dr. Twig has no disclosures. Dr. Sattar has consulted for or received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics through his institution.

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Transgender and nonbinary adolescents are twice as likely to experience sexual violence as their cisgendered peers but are less likely to attempt rape or commit sexual assault, researchers have found.

The study, which was published online  in JAMA Network Open, is among the first on the sexual violence that trans, nonbinary, and other gender nonconforming adolescents experience. Previous studies have focused on adults.

“In the busy world of clinical care, it is essential that clinicians be aware of potential disparities their patients are navigating,” said Michele Ybarra, PhD, MPH, president and research director of the Center for Innovative Public Health Research, San Clemente, California, who led the study. “This includes sexual violence victimization for gender minority youth and the need to talk about consent and boundaries for youth of all genders.”

Dr. Ybarra said that while clinicians may be aware that transgender young people face stigma, discrimination, and bullying, they may not be aware that trans youth are also the targets of sexual violence.

Studies indicate that health care providers and communities have significant misconceptions about sexually explicit behavior among trans and nonbinary teens. Misconceptions can lead to discrimination, resulting in higher rates of drug abuse, dropping out of school, suicide, and homelessness.

Dr. Ybarra and her colleagues surveyed 911 trans, nonbinary, or questioning youth on Instagram and Facebook through a collaboration with Growing Up With Media, a national longitudinal survey designed to investigate sexual violence during adolescence.

They also surveyed 3,282 cisgender persons aged 14-16 years who were recruited to the study between June 2018 and March 2020. The term “cisgender” refers to youth who identify with their gender at birth.

The questionnaires asked teens about gender identity, race, economic status, and support systems at home. Factors associated with not experiencing sexual violence included having a strong network of friends, family, and educators; involvement in the community; and having people close who affirm their gender identity.

More than three-fourths (78%) of youth surveyed identified as cisgender, 13.9% identified as questioning, and 7.9% identified as transgender.

Roughly two-thirds (67%) of transgender adolescents said they had experienced serious sexual violence, 73% reported experiencing violence in their communities, and 63% said they had been exposed to aggressive behavior. In contrast, 6.7% of trans youth said they had ever committed sexual violence, while 7.4% of cisgender teens surveyed, or 243 students, said they had done so.

“The relative lack of visibility of gender minority youth in sexual violence research is unacceptable,” Dr. Ybarra told this news organization. “To be counted, one needs to be seen. We aimed to start addressing this exclusion with the current study.”

The findings provide a lens into the levels of sexual violence that LGBTQIA+ youth experience and an opportunity to provide more inclusive care, according to Elizabeth Miller, MD, PhD, FSAHM, Distinguished Professor of Pediatrics, director of the Division of Adolescent and Young Adult Medicine, and medical director of community and population health at UPMC Children’s Hospital of Pittsburgh, who was not involved in the study.

“There are unfortunately pervasive and harmful stereotypes in our society about the ‘sexual deviancy’ attributed to LGBTQIA+ individuals,” Dr. Miller told this news organization. “This study adds to the research literature that counters and challenges these harmful – and inaccurate – perceptions.”

Dr. Miller said clinicians can help this population by offering youth accurate information about relevant support and services, including how to help a friend.

Programs that providers could incorporate include gender transformative approaches, which guide youth to examine gender norms and inequities and that develop leadership skills.

Such programs are more common outside the United States and have been shown to decrease LGBTQIA+ youth exposure to sexual violence, she said.

Dr. Miller said more research is needed to understand the contexts in which gender minority youth experience sexual violence to guide prevention efforts: “We need to move beyond individual-focused interventions to considering community-level interventions to create safer and more inclusive spaces for all youth.”

Dr. Miller has received royalties for writing content for UptoDate Wolters Kluwer outside of the current study. Dr. Ybarra has disclosed no relevant financial relationships.

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

Transgender and nonbinary adolescents are twice as likely to experience sexual violence as their cisgendered peers but are less likely to attempt rape or commit sexual assault, researchers have found.

The study, which was published online  in JAMA Network Open, is among the first on the sexual violence that trans, nonbinary, and other gender nonconforming adolescents experience. Previous studies have focused on adults.

“In the busy world of clinical care, it is essential that clinicians be aware of potential disparities their patients are navigating,” said Michele Ybarra, PhD, MPH, president and research director of the Center for Innovative Public Health Research, San Clemente, California, who led the study. “This includes sexual violence victimization for gender minority youth and the need to talk about consent and boundaries for youth of all genders.”

Dr. Ybarra said that while clinicians may be aware that transgender young people face stigma, discrimination, and bullying, they may not be aware that trans youth are also the targets of sexual violence.

Studies indicate that health care providers and communities have significant misconceptions about sexually explicit behavior among trans and nonbinary teens. Misconceptions can lead to discrimination, resulting in higher rates of drug abuse, dropping out of school, suicide, and homelessness.

Dr. Ybarra and her colleagues surveyed 911 trans, nonbinary, or questioning youth on Instagram and Facebook through a collaboration with Growing Up With Media, a national longitudinal survey designed to investigate sexual violence during adolescence.

They also surveyed 3,282 cisgender persons aged 14-16 years who were recruited to the study between June 2018 and March 2020. The term “cisgender” refers to youth who identify with their gender at birth.

The questionnaires asked teens about gender identity, race, economic status, and support systems at home. Factors associated with not experiencing sexual violence included having a strong network of friends, family, and educators; involvement in the community; and having people close who affirm their gender identity.

More than three-fourths (78%) of youth surveyed identified as cisgender, 13.9% identified as questioning, and 7.9% identified as transgender.

Roughly two-thirds (67%) of transgender adolescents said they had experienced serious sexual violence, 73% reported experiencing violence in their communities, and 63% said they had been exposed to aggressive behavior. In contrast, 6.7% of trans youth said they had ever committed sexual violence, while 7.4% of cisgender teens surveyed, or 243 students, said they had done so.

“The relative lack of visibility of gender minority youth in sexual violence research is unacceptable,” Dr. Ybarra told this news organization. “To be counted, one needs to be seen. We aimed to start addressing this exclusion with the current study.”

The findings provide a lens into the levels of sexual violence that LGBTQIA+ youth experience and an opportunity to provide more inclusive care, according to Elizabeth Miller, MD, PhD, FSAHM, Distinguished Professor of Pediatrics, director of the Division of Adolescent and Young Adult Medicine, and medical director of community and population health at UPMC Children’s Hospital of Pittsburgh, who was not involved in the study.

“There are unfortunately pervasive and harmful stereotypes in our society about the ‘sexual deviancy’ attributed to LGBTQIA+ individuals,” Dr. Miller told this news organization. “This study adds to the research literature that counters and challenges these harmful – and inaccurate – perceptions.”

Dr. Miller said clinicians can help this population by offering youth accurate information about relevant support and services, including how to help a friend.

Programs that providers could incorporate include gender transformative approaches, which guide youth to examine gender norms and inequities and that develop leadership skills.

Such programs are more common outside the United States and have been shown to decrease LGBTQIA+ youth exposure to sexual violence, she said.

Dr. Miller said more research is needed to understand the contexts in which gender minority youth experience sexual violence to guide prevention efforts: “We need to move beyond individual-focused interventions to considering community-level interventions to create safer and more inclusive spaces for all youth.”

Dr. Miller has received royalties for writing content for UptoDate Wolters Kluwer outside of the current study. Dr. Ybarra has disclosed no relevant financial relationships.

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

Transgender and nonbinary adolescents are twice as likely to experience sexual violence as their cisgendered peers but are less likely to attempt rape or commit sexual assault, researchers have found.

The study, which was published online  in JAMA Network Open, is among the first on the sexual violence that trans, nonbinary, and other gender nonconforming adolescents experience. Previous studies have focused on adults.

“In the busy world of clinical care, it is essential that clinicians be aware of potential disparities their patients are navigating,” said Michele Ybarra, PhD, MPH, president and research director of the Center for Innovative Public Health Research, San Clemente, California, who led the study. “This includes sexual violence victimization for gender minority youth and the need to talk about consent and boundaries for youth of all genders.”

Dr. Ybarra said that while clinicians may be aware that transgender young people face stigma, discrimination, and bullying, they may not be aware that trans youth are also the targets of sexual violence.

Studies indicate that health care providers and communities have significant misconceptions about sexually explicit behavior among trans and nonbinary teens. Misconceptions can lead to discrimination, resulting in higher rates of drug abuse, dropping out of school, suicide, and homelessness.

Dr. Ybarra and her colleagues surveyed 911 trans, nonbinary, or questioning youth on Instagram and Facebook through a collaboration with Growing Up With Media, a national longitudinal survey designed to investigate sexual violence during adolescence.

They also surveyed 3,282 cisgender persons aged 14-16 years who were recruited to the study between June 2018 and March 2020. The term “cisgender” refers to youth who identify with their gender at birth.

The questionnaires asked teens about gender identity, race, economic status, and support systems at home. Factors associated with not experiencing sexual violence included having a strong network of friends, family, and educators; involvement in the community; and having people close who affirm their gender identity.

More than three-fourths (78%) of youth surveyed identified as cisgender, 13.9% identified as questioning, and 7.9% identified as transgender.

Roughly two-thirds (67%) of transgender adolescents said they had experienced serious sexual violence, 73% reported experiencing violence in their communities, and 63% said they had been exposed to aggressive behavior. In contrast, 6.7% of trans youth said they had ever committed sexual violence, while 7.4% of cisgender teens surveyed, or 243 students, said they had done so.

“The relative lack of visibility of gender minority youth in sexual violence research is unacceptable,” Dr. Ybarra told this news organization. “To be counted, one needs to be seen. We aimed to start addressing this exclusion with the current study.”

The findings provide a lens into the levels of sexual violence that LGBTQIA+ youth experience and an opportunity to provide more inclusive care, according to Elizabeth Miller, MD, PhD, FSAHM, Distinguished Professor of Pediatrics, director of the Division of Adolescent and Young Adult Medicine, and medical director of community and population health at UPMC Children’s Hospital of Pittsburgh, who was not involved in the study.

“There are unfortunately pervasive and harmful stereotypes in our society about the ‘sexual deviancy’ attributed to LGBTQIA+ individuals,” Dr. Miller told this news organization. “This study adds to the research literature that counters and challenges these harmful – and inaccurate – perceptions.”

Dr. Miller said clinicians can help this population by offering youth accurate information about relevant support and services, including how to help a friend.

Programs that providers could incorporate include gender transformative approaches, which guide youth to examine gender norms and inequities and that develop leadership skills.

Such programs are more common outside the United States and have been shown to decrease LGBTQIA+ youth exposure to sexual violence, she said.

Dr. Miller said more research is needed to understand the contexts in which gender minority youth experience sexual violence to guide prevention efforts: “We need to move beyond individual-focused interventions to considering community-level interventions to create safer and more inclusive spaces for all youth.”

Dr. Miller has received royalties for writing content for UptoDate Wolters Kluwer outside of the current study. Dr. Ybarra has disclosed no relevant financial relationships.

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