MDedge Endocrinology

A small, nonmechanical, implanted device that continuously releases the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) and designed for improving glucose control in people with type 2 diabetes received a resounding, unanimous rejection Sept. 21 from an advisory committee of the Food and Drug Administration.

The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.

“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
 

“No evidence of improved adherence”

Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.

However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
 

Seven years of FDA review

This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.

Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week. 

But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”

All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

A small, nonmechanical, implanted device that continuously releases the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) and designed for improving glucose control in people with type 2 diabetes received a resounding, unanimous rejection Sept. 21 from an advisory committee of the Food and Drug Administration.

The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.

“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
 

“No evidence of improved adherence”

Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.

However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
 

Seven years of FDA review

This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.

Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week. 

But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”

All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

A small, nonmechanical, implanted device that continuously releases the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) and designed for improving glucose control in people with type 2 diabetes received a resounding, unanimous rejection Sept. 21 from an advisory committee of the Food and Drug Administration.

The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.

“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
 

“No evidence of improved adherence”

Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.

However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
 

Seven years of FDA review

This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.

Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week. 

But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”

All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Exercising in the morning may have the biggest impact on the likelihood of having obesity, whereas morning and afternoon exercise appear to reduce the risk of developing type 2 diabetes, suggest two studies.

Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.

The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.

For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.

However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.

Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
 

Morning exercisers perform less physical activity

Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”

The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.

They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.

The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).

The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.

Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).

Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).

Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).

Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).

The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.

“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.

However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.

“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
 

No association between evening activity and type 2 diabetes risk

In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.

The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.

After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.

However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).

The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.

Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

Exercising in the morning may have the biggest impact on the likelihood of having obesity, whereas morning and afternoon exercise appear to reduce the risk of developing type 2 diabetes, suggest two studies.

Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.

The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.

For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.

However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.

Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
 

Morning exercisers perform less physical activity

Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”

The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.

They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.

The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).

The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.

Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).

Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).

Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).

Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).

The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.

“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.

However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.

“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
 

No association between evening activity and type 2 diabetes risk

In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.

The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.

After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.

However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).

The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.

Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

Exercising in the morning may have the biggest impact on the likelihood of having obesity, whereas morning and afternoon exercise appear to reduce the risk of developing type 2 diabetes, suggest two studies.

Tongyu Ma, PhD, research assistant professor with the Health Sciences Department, Franklin Pierce University, Rindge, N.H., and colleagues studied data on almost 5,300 individuals, finding a strong association between moderate to vigorous physical activity (MVPA) and obesity.

The research, published in Obesity, showed that people who exercised in the morning had a lower body mass index than that of those who exercised at other times, even though they were more sedentary.

For the second study, Chirag J. Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, and colleagues examined more than 93,000 individuals and found that morning and afternoon, but not evening, exercise reduced the risk for type 2 diabetes.

However, the results, published in Diabetologia, also indicated that people who undertook at least MVPA were protected against developing type 2 diabetes no matter what time of day they exercised.

Along with considering the timing of exercise, the authors suggest that it is “helpful to include some higher intensity activity to help reduce the risk of developing diabetes and other cardiovascular disease.”
 

Morning exercisers perform less physical activity

Dr. Ma and colleagues noted that “although a beneficial association among the levels of physical activity with obesity has been frequently reported, the optimal timing of physical activity for decreasing obesity remains controversial.”

The researchers analyzed data from the National Health and Nutrition Examination Survey for the 2003-2004 and 2005-2006 cycles, because accelerometry was implemented in those periods.

They included 5,285 individuals aged ≥ 20 years who had physical activity measured via an accelerometer worn on the right hip during waking hours for 7 consecutive days.

The diurnal pattern of MVPA was classified into three clusters by the established technique of K-means clustering analysis: morning (n = 642), midday (n = 2,456), and evening (n = 2,187).

The association between MVPA, diurnal pattern, and obesity was then assessed in linear regression models taking into account a range of potential confounding factors.

Overall, participants in the morning cluster were older and more likely to be female than those in the other clusters (P < .001 for both). They were also more likely to be nonsmokers (P = .007) and to have less than high school education (P = .0041).

Morning cluster individuals performed less physical activity and were more sedentary than those in the midday and evening groups (P < .001 for both), although they were more likely to be healthy eaters (P = .004), with a lower calorie intake (P < .001).

Individuals in the morning cluster had, on average, a lower body mass index than those in other clusters, at 27.4 vs. 28.4 in the midday cluster and 28.2 in the evening cluster (P for interaction = .02).

Morning cluster participants also had a lower waist circumference than participants in the midday or evening cluster: 95.9 cm, 97.9 cm, and 97.3 cm, respectively (P for interaction = .06).

The team reported that there was a strong linear association between MVPA and obesity in the morning cluster, whereas there was a weaker curvilinear association in the midday and evening clusters.

“This is exciting new research that is consistent with a common tip for meeting exercise goals – that is, schedule exercise in the morning before emails, phone calls, or meetings that might distract you,” Rebecca Krukowski, PhD, professor, public health sciences, University of Virginia, Charlottesville, said in a release.

However, she noted that the cross-sectional nature of the study means that it is “not known whether people who exercise consistently in the morning may be systematically different from those who exercise at other times, in ways that were not measured in this study.

“For example, people who exercise regularly in the morning could have more predictable schedules, such as being less likely to be shift workers or less likely to have caregiving responsibilities that impede morning exercise,” said Dr. Krukowski, who was not involved in the study.
 

No association between evening activity and type 2 diabetes risk

In the second study, the team studied 93,095 persons in the UK Biobank, with a mean age of 62 years and no history of type 2 diabetes, who wore a wrist accelerometer for 1 week.

The movement data were used to estimate the metabolic equivalent of task, which was then summed into the total physical activity completed in the morning, afternoon, and evening and linked to the development of incident type 2 diabetes.

After adjustment for potential confounding factors, both morning and afternoon physical activity were associated with a reduced risk of developing type 2 diabetes, at hazard ratios of 0.90 (P = 7 × 10-8) and 0.91 (P = 1 × 10-5), respectively.

However, there was no association between evening activity and the risk for type 2 diabetes, at a hazard ratio of 0.95 (P = .07).

The team found, however, that MVPA and vigorous physical activity were associated with a reduced risk for type 2 diabetes at all times of day.

Dr. Patel’s study was supported in part by National Institutes of Health grants. No other funding was declared. No relevant financial relationships were declared.

A version of this article appeared on Medscape.com.

A significant mortality gap persists between patients with type 2 diabetes and cardiovascular disease and similarly aged patients with neither condition. Data from the Emerging Risk Factors Collaboration showed that on average, a 60-year-old female patient with type 2 diabetes and a history of myocardial infarction dies around 14 years earlier than a similarly aged patient with neither of these conditions.

Therefore, I was keen to hear the key new recommendations from the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiovascular disease in patients with diabetes. These recommendations were presented at the recent ESC 2023 congress in Amsterdam, which I was fortunate enough to attend.

The comprehensive guideline cemented the fact that our primary goal in type 2 diabetes management is a reduction in cardiovascular events and mortality, rather than the glucocentric goals that have been followed previously. Of course, good glycemic control remains important to protect against the microvascular complications of diabetes, but glycemic control has only a modest impact on macrovascular complications such as cardiovascular disease.

The updated guideline recommends that all patients with type 2 diabetes without symptomatic atherosclerotic cardiovascular disease or severe target-organ damage be screened for the risk for cardiovascular disease using a new 10-year cardiovascular risk calculator called SCORE2-Diabetes. This calculator extends the well-established SCORE2 cardiovascular risk-prediction tool with added predictors specifically related to type 2 diabetes. It also accounts for variation in risk across Europe.

Using SCORE2 Diabetes will be a change in practice for me, as I have been using QRISK3, which is a United Kingdom–based cardiovascular risk tool that has been less extensively validated in patients with type 2 diabetes. Helpfully, an ESC CVD Risk Calculation app is available and can be tailored to your geographical region to calculate a SCORE2-Diabetes risk score easily. For example, Eastern Europe has a higher cardiovascular risk profile than Western Europe.

Cardiovascular risk categories are now defined on the basis of the presence of atherosclerotic cardiovascular disease, severe target-organ damage, or the 10-year cardiovascular risk using SCORE2-Diabetes.

For patients at very high cardiovascular risk (for example, those with type 2 diabetes and established atherosclerotic cardiovascular disease), the ESC guidance recommends dual therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor to reduce cardiovascular risk independent of glucose control (that is, A1c). This dual therapy is recommended in addition to standard-of-care antiplatelet, antihypertensive, and lipid-lowering therapies.

There is no doubt that the evidence for GLP-1 receptor agonist use and reduction in atherosclerotic cardiovascular disease in type 2 diabetes is compelling, perhaps more so than the evidence for SGLT2 inhibitor use. However, this recommendation will be challenging to implement, given the current global supply issues with GLP-1 receptor agonists, which are driven by the off-label use of these medications for the management of obesity. GLP-1 receptor agonist supplies are not expected to stabilize until mid-2024.

Controversially, the updated ESC guidance suggests the use of metformin only in patients with type 2 diabetes and atherosclerotic cardiovascular disease if additional glucose control is required. This is a misstep, in my opinion, as insulin resistance is one of the key pathophysiologic abnormalities in patients with type 2 diabetes. One of the key advantages of metformin is an improvement in insulin sensitivity. This recommendation will not change my practice, and I will continue to prescribe metformin alongside GLP-1 receptor agonists or SGLT2 inhibitors for my patients at highest cardiovascular risk.

The updated ESC guidance also explicitly reminds healthcare professionals to look for significant comorbidities, such as heart failure of all subtypes and chronic kidney disease.

The ESC guidance recommends a systematic survey for heart failure symptoms and signs at each clinical encounter in all patients with type 2 diabetes. Although I agree that heart failure is underdiagnosed in this population, the recommendation will be challenging to implement and has significant workload implications, as heart failure often presents in insidious, nonspecific ways in primary care.

For patients with type 2 diabetes and heart failure with reduced ejection fraction, SGLT2 inhibitors are recommended to reduce the risk for heart failure hospitalization and cardiovascular death. Again, this recommendation is independent of glycemic control. In addition, for patients with type 2 diabetes and heart failure with mid-range ejection fraction or heart failure with preserved ejection fraction (that is, left ventricular ejection fraction > 40%), SGLT2 inhibitors are also recommended to reduce the risk for heart failure hospitalization or cardiovascular death independent of glycemic control. This recommendation is consistent with other updated global heart failure guidance. Increasingly, the pillars of heart failure therapy are being challenged with the early initiation of SGLT2 inhibitors, given their compelling evidence base, early symptomatic benefit, and ease of use, with less requirement of routine blood monitoring.

Finally, for patients with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors and finerenone are now recommended to reduce the risk for kidney failure and cardiovascular disease, independent of glycemic control and in addition to standard of care.

Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist with quite different pharmacokinetics and clinical effects, compared with those of spironolactone and eplerenone, which are steroidal MRAs. Specifically, finerenone does not significantly lower blood pressure and has fewer steroid-induced adverse effects such as gynecomastia, impotence, and low libido. However, like steroidal MRAs, finerenone can result in hyperkalemia.

Finerenone has demonstrated significant kidney and cardiovascular benefits across the spectrum of chronic kidney disease in patients with type 2 diabetes. It entails no significant imbalance in adverse events, hence this recommendation. This observation reinforces the importance of measuring urinary albumin–creatinine ratio in patients with type 2 diabetes and preserved kidney function.

In conclusion, the 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes are forward-thinking recommendations. They look beyond glycemia and reflect the current evidence for newer glucose-lowering therapies with proven cardiorenal benefits. Nevertheless, the implementation of these guidelines will be challenging, given their workload implications, the unstable supply of GLP-1 receptor agonists, and a persisting glucocentric approach to type 2 diabetes care in some areas. Implementation will require ongoing education for health care professionals about the risk-benefit ratios of SGLT2 inhibitors and GLP-1 receptor agonists. It also will require a re-evaluation of workforce strategy to support the development of a skilled and sustainable workforce.

Dr. Fernando is a general practitioner partner with North Berwick (Scotland) Health Centre, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education. He disclosed receiving speakers’ fees from Eli Lilly and Novo Nordisk.

A version of this article appeared on Medscape.com.

A significant mortality gap persists between patients with type 2 diabetes and cardiovascular disease and similarly aged patients with neither condition. Data from the Emerging Risk Factors Collaboration showed that on average, a 60-year-old female patient with type 2 diabetes and a history of myocardial infarction dies around 14 years earlier than a similarly aged patient with neither of these conditions.

Therefore, I was keen to hear the key new recommendations from the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiovascular disease in patients with diabetes. These recommendations were presented at the recent ESC 2023 congress in Amsterdam, which I was fortunate enough to attend.

The comprehensive guideline cemented the fact that our primary goal in type 2 diabetes management is a reduction in cardiovascular events and mortality, rather than the glucocentric goals that have been followed previously. Of course, good glycemic control remains important to protect against the microvascular complications of diabetes, but glycemic control has only a modest impact on macrovascular complications such as cardiovascular disease.

The updated guideline recommends that all patients with type 2 diabetes without symptomatic atherosclerotic cardiovascular disease or severe target-organ damage be screened for the risk for cardiovascular disease using a new 10-year cardiovascular risk calculator called SCORE2-Diabetes. This calculator extends the well-established SCORE2 cardiovascular risk-prediction tool with added predictors specifically related to type 2 diabetes. It also accounts for variation in risk across Europe.

Using SCORE2 Diabetes will be a change in practice for me, as I have been using QRISK3, which is a United Kingdom–based cardiovascular risk tool that has been less extensively validated in patients with type 2 diabetes. Helpfully, an ESC CVD Risk Calculation app is available and can be tailored to your geographical region to calculate a SCORE2-Diabetes risk score easily. For example, Eastern Europe has a higher cardiovascular risk profile than Western Europe.

Cardiovascular risk categories are now defined on the basis of the presence of atherosclerotic cardiovascular disease, severe target-organ damage, or the 10-year cardiovascular risk using SCORE2-Diabetes.

For patients at very high cardiovascular risk (for example, those with type 2 diabetes and established atherosclerotic cardiovascular disease), the ESC guidance recommends dual therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor to reduce cardiovascular risk independent of glucose control (that is, A1c). This dual therapy is recommended in addition to standard-of-care antiplatelet, antihypertensive, and lipid-lowering therapies.

There is no doubt that the evidence for GLP-1 receptor agonist use and reduction in atherosclerotic cardiovascular disease in type 2 diabetes is compelling, perhaps more so than the evidence for SGLT2 inhibitor use. However, this recommendation will be challenging to implement, given the current global supply issues with GLP-1 receptor agonists, which are driven by the off-label use of these medications for the management of obesity. GLP-1 receptor agonist supplies are not expected to stabilize until mid-2024.

Controversially, the updated ESC guidance suggests the use of metformin only in patients with type 2 diabetes and atherosclerotic cardiovascular disease if additional glucose control is required. This is a misstep, in my opinion, as insulin resistance is one of the key pathophysiologic abnormalities in patients with type 2 diabetes. One of the key advantages of metformin is an improvement in insulin sensitivity. This recommendation will not change my practice, and I will continue to prescribe metformin alongside GLP-1 receptor agonists or SGLT2 inhibitors for my patients at highest cardiovascular risk.

The updated ESC guidance also explicitly reminds healthcare professionals to look for significant comorbidities, such as heart failure of all subtypes and chronic kidney disease.

The ESC guidance recommends a systematic survey for heart failure symptoms and signs at each clinical encounter in all patients with type 2 diabetes. Although I agree that heart failure is underdiagnosed in this population, the recommendation will be challenging to implement and has significant workload implications, as heart failure often presents in insidious, nonspecific ways in primary care.

For patients with type 2 diabetes and heart failure with reduced ejection fraction, SGLT2 inhibitors are recommended to reduce the risk for heart failure hospitalization and cardiovascular death. Again, this recommendation is independent of glycemic control. In addition, for patients with type 2 diabetes and heart failure with mid-range ejection fraction or heart failure with preserved ejection fraction (that is, left ventricular ejection fraction > 40%), SGLT2 inhibitors are also recommended to reduce the risk for heart failure hospitalization or cardiovascular death independent of glycemic control. This recommendation is consistent with other updated global heart failure guidance. Increasingly, the pillars of heart failure therapy are being challenged with the early initiation of SGLT2 inhibitors, given their compelling evidence base, early symptomatic benefit, and ease of use, with less requirement of routine blood monitoring.

Finally, for patients with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors and finerenone are now recommended to reduce the risk for kidney failure and cardiovascular disease, independent of glycemic control and in addition to standard of care.

Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist with quite different pharmacokinetics and clinical effects, compared with those of spironolactone and eplerenone, which are steroidal MRAs. Specifically, finerenone does not significantly lower blood pressure and has fewer steroid-induced adverse effects such as gynecomastia, impotence, and low libido. However, like steroidal MRAs, finerenone can result in hyperkalemia.

Finerenone has demonstrated significant kidney and cardiovascular benefits across the spectrum of chronic kidney disease in patients with type 2 diabetes. It entails no significant imbalance in adverse events, hence this recommendation. This observation reinforces the importance of measuring urinary albumin–creatinine ratio in patients with type 2 diabetes and preserved kidney function.

In conclusion, the 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes are forward-thinking recommendations. They look beyond glycemia and reflect the current evidence for newer glucose-lowering therapies with proven cardiorenal benefits. Nevertheless, the implementation of these guidelines will be challenging, given their workload implications, the unstable supply of GLP-1 receptor agonists, and a persisting glucocentric approach to type 2 diabetes care in some areas. Implementation will require ongoing education for health care professionals about the risk-benefit ratios of SGLT2 inhibitors and GLP-1 receptor agonists. It also will require a re-evaluation of workforce strategy to support the development of a skilled and sustainable workforce.

Dr. Fernando is a general practitioner partner with North Berwick (Scotland) Health Centre, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education. He disclosed receiving speakers’ fees from Eli Lilly and Novo Nordisk.

A version of this article appeared on Medscape.com.

A significant mortality gap persists between patients with type 2 diabetes and cardiovascular disease and similarly aged patients with neither condition. Data from the Emerging Risk Factors Collaboration showed that on average, a 60-year-old female patient with type 2 diabetes and a history of myocardial infarction dies around 14 years earlier than a similarly aged patient with neither of these conditions.

Therefore, I was keen to hear the key new recommendations from the 2023 European Society of Cardiology (ESC) guidelines for the management of cardiovascular disease in patients with diabetes. These recommendations were presented at the recent ESC 2023 congress in Amsterdam, which I was fortunate enough to attend.

The comprehensive guideline cemented the fact that our primary goal in type 2 diabetes management is a reduction in cardiovascular events and mortality, rather than the glucocentric goals that have been followed previously. Of course, good glycemic control remains important to protect against the microvascular complications of diabetes, but glycemic control has only a modest impact on macrovascular complications such as cardiovascular disease.

The updated guideline recommends that all patients with type 2 diabetes without symptomatic atherosclerotic cardiovascular disease or severe target-organ damage be screened for the risk for cardiovascular disease using a new 10-year cardiovascular risk calculator called SCORE2-Diabetes. This calculator extends the well-established SCORE2 cardiovascular risk-prediction tool with added predictors specifically related to type 2 diabetes. It also accounts for variation in risk across Europe.

Using SCORE2 Diabetes will be a change in practice for me, as I have been using QRISK3, which is a United Kingdom–based cardiovascular risk tool that has been less extensively validated in patients with type 2 diabetes. Helpfully, an ESC CVD Risk Calculation app is available and can be tailored to your geographical region to calculate a SCORE2-Diabetes risk score easily. For example, Eastern Europe has a higher cardiovascular risk profile than Western Europe.

Cardiovascular risk categories are now defined on the basis of the presence of atherosclerotic cardiovascular disease, severe target-organ damage, or the 10-year cardiovascular risk using SCORE2-Diabetes.

For patients at very high cardiovascular risk (for example, those with type 2 diabetes and established atherosclerotic cardiovascular disease), the ESC guidance recommends dual therapy with a GLP-1 receptor agonist and an SGLT2 inhibitor to reduce cardiovascular risk independent of glucose control (that is, A1c). This dual therapy is recommended in addition to standard-of-care antiplatelet, antihypertensive, and lipid-lowering therapies.

There is no doubt that the evidence for GLP-1 receptor agonist use and reduction in atherosclerotic cardiovascular disease in type 2 diabetes is compelling, perhaps more so than the evidence for SGLT2 inhibitor use. However, this recommendation will be challenging to implement, given the current global supply issues with GLP-1 receptor agonists, which are driven by the off-label use of these medications for the management of obesity. GLP-1 receptor agonist supplies are not expected to stabilize until mid-2024.

Controversially, the updated ESC guidance suggests the use of metformin only in patients with type 2 diabetes and atherosclerotic cardiovascular disease if additional glucose control is required. This is a misstep, in my opinion, as insulin resistance is one of the key pathophysiologic abnormalities in patients with type 2 diabetes. One of the key advantages of metformin is an improvement in insulin sensitivity. This recommendation will not change my practice, and I will continue to prescribe metformin alongside GLP-1 receptor agonists or SGLT2 inhibitors for my patients at highest cardiovascular risk.

The updated ESC guidance also explicitly reminds healthcare professionals to look for significant comorbidities, such as heart failure of all subtypes and chronic kidney disease.

The ESC guidance recommends a systematic survey for heart failure symptoms and signs at each clinical encounter in all patients with type 2 diabetes. Although I agree that heart failure is underdiagnosed in this population, the recommendation will be challenging to implement and has significant workload implications, as heart failure often presents in insidious, nonspecific ways in primary care.

For patients with type 2 diabetes and heart failure with reduced ejection fraction, SGLT2 inhibitors are recommended to reduce the risk for heart failure hospitalization and cardiovascular death. Again, this recommendation is independent of glycemic control. In addition, for patients with type 2 diabetes and heart failure with mid-range ejection fraction or heart failure with preserved ejection fraction (that is, left ventricular ejection fraction > 40%), SGLT2 inhibitors are also recommended to reduce the risk for heart failure hospitalization or cardiovascular death independent of glycemic control. This recommendation is consistent with other updated global heart failure guidance. Increasingly, the pillars of heart failure therapy are being challenged with the early initiation of SGLT2 inhibitors, given their compelling evidence base, early symptomatic benefit, and ease of use, with less requirement of routine blood monitoring.

Finally, for patients with type 2 diabetes and chronic kidney disease, SGLT2 inhibitors and finerenone are now recommended to reduce the risk for kidney failure and cardiovascular disease, independent of glycemic control and in addition to standard of care.

Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist with quite different pharmacokinetics and clinical effects, compared with those of spironolactone and eplerenone, which are steroidal MRAs. Specifically, finerenone does not significantly lower blood pressure and has fewer steroid-induced adverse effects such as gynecomastia, impotence, and low libido. However, like steroidal MRAs, finerenone can result in hyperkalemia.

Finerenone has demonstrated significant kidney and cardiovascular benefits across the spectrum of chronic kidney disease in patients with type 2 diabetes. It entails no significant imbalance in adverse events, hence this recommendation. This observation reinforces the importance of measuring urinary albumin–creatinine ratio in patients with type 2 diabetes and preserved kidney function.

In conclusion, the 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes are forward-thinking recommendations. They look beyond glycemia and reflect the current evidence for newer glucose-lowering therapies with proven cardiorenal benefits. Nevertheless, the implementation of these guidelines will be challenging, given their workload implications, the unstable supply of GLP-1 receptor agonists, and a persisting glucocentric approach to type 2 diabetes care in some areas. Implementation will require ongoing education for health care professionals about the risk-benefit ratios of SGLT2 inhibitors and GLP-1 receptor agonists. It also will require a re-evaluation of workforce strategy to support the development of a skilled and sustainable workforce.

Dr. Fernando is a general practitioner partner with North Berwick (Scotland) Health Centre, with a specialist interest in diabetes; cardiovascular, renal, and metabolic diseases; and medical education. He disclosed receiving speakers’ fees from Eli Lilly and Novo Nordisk.

A version of this article appeared on Medscape.com.

TOPLINE:

Compared with body mass index, waist-hip ratio (WHR) had the strongest and most consistent association with all-cause mortality and was the only measurement unaffected by BMI.

METHODOLOGY:

• Cohort study of incident deaths from the U.K. Biobank (2006-2022), including data from 22 centers across the United Kingdom.
• A total of 387,672 participants were divided into a discovery cohort (n = 337,078) and validation cohort (n = 50,594), with the latter consisting of 25,297 deaths and 2,297 controls.
• The discovery cohort was used to derive genetically determined adiposity measures while the validation cohort was used for analyses.
• Exposure-outcome associations were analyzed through observational and mendelian randomization analyses.

TAKEAWAY:

• In adjusted analysis, a J-shaped association was found for both measured BMI and fat mass index (FMI), whereas the association with WHR was linear (hazard ratio 1.41 per standard deviation increase).
• There was a significant association between all three adiposity measures and all-cause mortality, with odds ratio 1.29 per SD change in genetically determined BMI (P = 1.44×10-13), 1.45 per SD change in genetically determined FMI, 1.45 (P = 6.27×10-30), and 1.51 per SD change in genetically determined WHR (P = 2.11×10-9).
• Compared with BMI, WHR had the stronger association with all-cause mortality, although it was not significantly stronger than FMI.
• The association of genetically determined BMI and FMI with all-cause mortality varied across quantiles of observed BMI, but WHR did not (P = .04, P = .02, and P = .58, for BMI, FMI, and WHR, respectively).

IN PRACTICE:

“Current World Health Organization recommendations for optimal BMI range are inaccurate across individuals with various body compositions and therefore suboptimal for clinical guidelines.”

SOURCE:

Study by Irfan Khan, MSc, of the Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Hamilton, Ont., and colleagues. Published online  in JAMA Network Open.

LIMITATIONS:

Study population was genetically homogeneous, White, and British, so results may not be representative of other racial or ethnic groups.

DISCLOSURES:

Study was funded by, and Irfan Khan received support from, the Ontario Graduate Scholarship–Masters Scholarship, awarded by the government of Ontario.

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

TOPLINE:

Compared with body mass index, waist-hip ratio (WHR) had the strongest and most consistent association with all-cause mortality and was the only measurement unaffected by BMI.

METHODOLOGY:

• Cohort study of incident deaths from the U.K. Biobank (2006-2022), including data from 22 centers across the United Kingdom.
• A total of 387,672 participants were divided into a discovery cohort (n = 337,078) and validation cohort (n = 50,594), with the latter consisting of 25,297 deaths and 2,297 controls.
• The discovery cohort was used to derive genetically determined adiposity measures while the validation cohort was used for analyses.
• Exposure-outcome associations were analyzed through observational and mendelian randomization analyses.

TAKEAWAY:

• In adjusted analysis, a J-shaped association was found for both measured BMI and fat mass index (FMI), whereas the association with WHR was linear (hazard ratio 1.41 per standard deviation increase).
• There was a significant association between all three adiposity measures and all-cause mortality, with odds ratio 1.29 per SD change in genetically determined BMI (P = 1.44×10-13), 1.45 per SD change in genetically determined FMI, 1.45 (P = 6.27×10-30), and 1.51 per SD change in genetically determined WHR (P = 2.11×10-9).
• Compared with BMI, WHR had the stronger association with all-cause mortality, although it was not significantly stronger than FMI.
• The association of genetically determined BMI and FMI with all-cause mortality varied across quantiles of observed BMI, but WHR did not (P = .04, P = .02, and P = .58, for BMI, FMI, and WHR, respectively).

IN PRACTICE:

“Current World Health Organization recommendations for optimal BMI range are inaccurate across individuals with various body compositions and therefore suboptimal for clinical guidelines.”

SOURCE:

Study by Irfan Khan, MSc, of the Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Hamilton, Ont., and colleagues. Published online  in JAMA Network Open.

LIMITATIONS:

Study population was genetically homogeneous, White, and British, so results may not be representative of other racial or ethnic groups.

DISCLOSURES:

Study was funded by, and Irfan Khan received support from, the Ontario Graduate Scholarship–Masters Scholarship, awarded by the government of Ontario.

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

TOPLINE:

Compared with body mass index, waist-hip ratio (WHR) had the strongest and most consistent association with all-cause mortality and was the only measurement unaffected by BMI.

METHODOLOGY:

• Cohort study of incident deaths from the U.K. Biobank (2006-2022), including data from 22 centers across the United Kingdom.
• A total of 387,672 participants were divided into a discovery cohort (n = 337,078) and validation cohort (n = 50,594), with the latter consisting of 25,297 deaths and 2,297 controls.
• The discovery cohort was used to derive genetically determined adiposity measures while the validation cohort was used for analyses.
• Exposure-outcome associations were analyzed through observational and mendelian randomization analyses.

TAKEAWAY:

• In adjusted analysis, a J-shaped association was found for both measured BMI and fat mass index (FMI), whereas the association with WHR was linear (hazard ratio 1.41 per standard deviation increase).
• There was a significant association between all three adiposity measures and all-cause mortality, with odds ratio 1.29 per SD change in genetically determined BMI (P = 1.44×10-13), 1.45 per SD change in genetically determined FMI, 1.45 (P = 6.27×10-30), and 1.51 per SD change in genetically determined WHR (P = 2.11×10-9).
• Compared with BMI, WHR had the stronger association with all-cause mortality, although it was not significantly stronger than FMI.
• The association of genetically determined BMI and FMI with all-cause mortality varied across quantiles of observed BMI, but WHR did not (P = .04, P = .02, and P = .58, for BMI, FMI, and WHR, respectively).

IN PRACTICE:

“Current World Health Organization recommendations for optimal BMI range are inaccurate across individuals with various body compositions and therefore suboptimal for clinical guidelines.”

SOURCE:

Study by Irfan Khan, MSc, of the Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Hamilton, Ont., and colleagues. Published online  in JAMA Network Open.

LIMITATIONS:

Study population was genetically homogeneous, White, and British, so results may not be representative of other racial or ethnic groups.

DISCLOSURES:

Study was funded by, and Irfan Khan received support from, the Ontario Graduate Scholarship–Masters Scholarship, awarded by the government of Ontario.

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

With ever-expanding treatment options for the ablation of benign thyroid nodules, the American Thyroid Association has issued an expert consensus statement that addresses the safe implementation and utilization of the techniques.

“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.

“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.

Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.

The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
 

Ablation methods can depend on nodule type

Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.

Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.

While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
 

Patient counseling – managing expectations

Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.

Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.

Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.

Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.

Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.

Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.

“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.

Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
 

Follow-up

For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.

Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.

Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
 

Learning curve

Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.

“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.

“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”

RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.

Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.

“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.

For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.

Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.

Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.

“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”

The authors’ disclosures are detailed in the published report.

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

With ever-expanding treatment options for the ablation of benign thyroid nodules, the American Thyroid Association has issued an expert consensus statement that addresses the safe implementation and utilization of the techniques.

“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.

“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.

Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.

The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
 

Ablation methods can depend on nodule type

Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.

Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.

While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
 

Patient counseling – managing expectations

Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.

Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.

Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.

Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.

Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.

Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.

“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.

Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
 

Follow-up

For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.

Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.

Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
 

Learning curve

Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.

“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.

“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”

RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.

Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.

“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.

For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.

Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.

Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.

“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”

The authors’ disclosures are detailed in the published report.

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

With ever-expanding treatment options for the ablation of benign thyroid nodules, the American Thyroid Association has issued an expert consensus statement that addresses the safe implementation and utilization of the techniques.

“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.

“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.

Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.

The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
 

Ablation methods can depend on nodule type

Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.

Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.

While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
 

Patient counseling – managing expectations

Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.

Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.

Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.

Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.

Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.

Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.

“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.

Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
 

Follow-up

For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.

Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.

Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
 

Learning curve

Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.

“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.

“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”

RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.

Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.

“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.

For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.

Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.

Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.

“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”

The authors’ disclosures are detailed in the published report.

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

This transcript has been edited for clarity.

Let’s assume, for the sake of argument, that I am a healthy 43-year old man. Nevertheless, I am interested in getting my vitamin D level checked. My primary care doc says it’s unnecessary, but that doesn’t matter because a variety of direct-to-consumer testing companies will do it without a doctor’s prescription – for a fee of course.

Is that okay? Should I be able to get the test?

What if instead of my vitamin D level, I want to test my testosterone level, or my PSA, or my cadmium level, or my Lyme disease antibodies, or even have a full-body MRI scan? All of these tests are available from a variety of direct-to-consumer testing companies. If I am willing to pay, should I be able to get those too?

These questions are becoming more and more common, because the direct-to-consumer testing market is exploding.

We’re talking about direct-to-consumer testing, thanks to this paper: Policies of US Companies Offering Direct-to-Consumer Laboratory Tests, appearing in JAMA Internal Medicine, which characterizes the testing practices of direct-to-consumer testing companies.

But before we get to the study, a word on this market. Direct-to-consumer lab testing is projected to be a $2 billion industry by 2025, and lab testing megacorporations Quest Diagnostics and Labcorp are both jumping headlong into this space.

Why is this happening? A couple of reasons, I think. First, the increasing cost of health care has led payers to place significant restrictions on what tests can be ordered and under what circumstances. Physicians are all too familiar with the “prior authorization” system that seeks to limit even the tests we think would benefit our patients.

Frustrated with such a system, it’s no wonder that patients are increasingly deciding to go it on their own. Sure, insurance won’t cover these tests, but the prices are transparent and competition actually keeps them somewhat reasonable. So, is this a win-win? Shouldn’t we allow people to get the tests they want, at least if they are willing to pay for it?

Of course, it’s not quite that simple. If the tests are normal, or negative, then sure – no harm, no foul. But when they are positive, everything changes. What happens when the PSA test I got myself via a direct-to-consumer testing company comes back elevated? Well, at that point, I am right back into the traditional mode of medicine – seeing my doctor, probably getting repeat testing, biopsies, etc., – and some payer will be on the hook for that, which is to say that all of us will be on the hook for that.

One other reason direct-to-consumer testing is getting more popular is a more difficult-to-characterize phenomenon which I might call postpandemic individualism. I’ve seen this across several domains, but I think in some ways the pandemic led people to focus more attention on themselves, perhaps because we were so isolated from each other. Optimizing health through data – whether using a fitness tracking watch, meticulously counting macronutrient intake, or ordering your own lab tests – may be a form of exerting control over a universe that feels increasingly chaotic. But what do I know? I’m not a psychologist.

The study characterizes a total of 21 direct-to-consumer testing companies. They offer a variety of services, as you can see here, with the majority in the endocrine space: thyroid, diabetes, men’s and women’s health. A smattering of companies offer more esoteric testing, such as heavy metals and Lyme disease.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no relevant conflicts of interest.

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

This transcript has been edited for clarity.

Let’s assume, for the sake of argument, that I am a healthy 43-year old man. Nevertheless, I am interested in getting my vitamin D level checked. My primary care doc says it’s unnecessary, but that doesn’t matter because a variety of direct-to-consumer testing companies will do it without a doctor’s prescription – for a fee of course.

Is that okay? Should I be able to get the test?

What if instead of my vitamin D level, I want to test my testosterone level, or my PSA, or my cadmium level, or my Lyme disease antibodies, or even have a full-body MRI scan? All of these tests are available from a variety of direct-to-consumer testing companies. If I am willing to pay, should I be able to get those too?

These questions are becoming more and more common, because the direct-to-consumer testing market is exploding.

We’re talking about direct-to-consumer testing, thanks to this paper: Policies of US Companies Offering Direct-to-Consumer Laboratory Tests, appearing in JAMA Internal Medicine, which characterizes the testing practices of direct-to-consumer testing companies.

But before we get to the study, a word on this market. Direct-to-consumer lab testing is projected to be a $2 billion industry by 2025, and lab testing megacorporations Quest Diagnostics and Labcorp are both jumping headlong into this space.

Why is this happening? A couple of reasons, I think. First, the increasing cost of health care has led payers to place significant restrictions on what tests can be ordered and under what circumstances. Physicians are all too familiar with the “prior authorization” system that seeks to limit even the tests we think would benefit our patients.

Frustrated with such a system, it’s no wonder that patients are increasingly deciding to go it on their own. Sure, insurance won’t cover these tests, but the prices are transparent and competition actually keeps them somewhat reasonable. So, is this a win-win? Shouldn’t we allow people to get the tests they want, at least if they are willing to pay for it?

Of course, it’s not quite that simple. If the tests are normal, or negative, then sure – no harm, no foul. But when they are positive, everything changes. What happens when the PSA test I got myself via a direct-to-consumer testing company comes back elevated? Well, at that point, I am right back into the traditional mode of medicine – seeing my doctor, probably getting repeat testing, biopsies, etc., – and some payer will be on the hook for that, which is to say that all of us will be on the hook for that.

One other reason direct-to-consumer testing is getting more popular is a more difficult-to-characterize phenomenon which I might call postpandemic individualism. I’ve seen this across several domains, but I think in some ways the pandemic led people to focus more attention on themselves, perhaps because we were so isolated from each other. Optimizing health through data – whether using a fitness tracking watch, meticulously counting macronutrient intake, or ordering your own lab tests – may be a form of exerting control over a universe that feels increasingly chaotic. But what do I know? I’m not a psychologist.

The study characterizes a total of 21 direct-to-consumer testing companies. They offer a variety of services, as you can see here, with the majority in the endocrine space: thyroid, diabetes, men’s and women’s health. A smattering of companies offer more esoteric testing, such as heavy metals and Lyme disease.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no relevant conflicts of interest.

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

This transcript has been edited for clarity.

Let’s assume, for the sake of argument, that I am a healthy 43-year old man. Nevertheless, I am interested in getting my vitamin D level checked. My primary care doc says it’s unnecessary, but that doesn’t matter because a variety of direct-to-consumer testing companies will do it without a doctor’s prescription – for a fee of course.

Is that okay? Should I be able to get the test?

What if instead of my vitamin D level, I want to test my testosterone level, or my PSA, or my cadmium level, or my Lyme disease antibodies, or even have a full-body MRI scan? All of these tests are available from a variety of direct-to-consumer testing companies. If I am willing to pay, should I be able to get those too?

These questions are becoming more and more common, because the direct-to-consumer testing market is exploding.

We’re talking about direct-to-consumer testing, thanks to this paper: Policies of US Companies Offering Direct-to-Consumer Laboratory Tests, appearing in JAMA Internal Medicine, which characterizes the testing practices of direct-to-consumer testing companies.

But before we get to the study, a word on this market. Direct-to-consumer lab testing is projected to be a $2 billion industry by 2025, and lab testing megacorporations Quest Diagnostics and Labcorp are both jumping headlong into this space.

Why is this happening? A couple of reasons, I think. First, the increasing cost of health care has led payers to place significant restrictions on what tests can be ordered and under what circumstances. Physicians are all too familiar with the “prior authorization” system that seeks to limit even the tests we think would benefit our patients.

Frustrated with such a system, it’s no wonder that patients are increasingly deciding to go it on their own. Sure, insurance won’t cover these tests, but the prices are transparent and competition actually keeps them somewhat reasonable. So, is this a win-win? Shouldn’t we allow people to get the tests they want, at least if they are willing to pay for it?

Of course, it’s not quite that simple. If the tests are normal, or negative, then sure – no harm, no foul. But when they are positive, everything changes. What happens when the PSA test I got myself via a direct-to-consumer testing company comes back elevated? Well, at that point, I am right back into the traditional mode of medicine – seeing my doctor, probably getting repeat testing, biopsies, etc., – and some payer will be on the hook for that, which is to say that all of us will be on the hook for that.

One other reason direct-to-consumer testing is getting more popular is a more difficult-to-characterize phenomenon which I might call postpandemic individualism. I’ve seen this across several domains, but I think in some ways the pandemic led people to focus more attention on themselves, perhaps because we were so isolated from each other. Optimizing health through data – whether using a fitness tracking watch, meticulously counting macronutrient intake, or ordering your own lab tests – may be a form of exerting control over a universe that feels increasingly chaotic. But what do I know? I’m not a psychologist.

The study characterizes a total of 21 direct-to-consumer testing companies. They offer a variety of services, as you can see here, with the majority in the endocrine space: thyroid, diabetes, men’s and women’s health. A smattering of companies offer more esoteric testing, such as heavy metals and Lyme disease.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no relevant conflicts of interest.

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

TOPLINE:

Patients with type 1 diabetes who received transplanted islets along with a kidney transplant had significantly reduced mortality and transplant failure risks, compared with those who received kidney alone and continued to use insulin.

METHODOLOGY:

• Study population was all patients with type 1 diabetes in France who received a kidney transplant between 2000 and 2017.
• Among 2,393 patients, 327 were eligible for islet transplantation, including 47 who were actually transplanted with islets.
• The subjects were matched for factors including year of transplantation, recipient age, kidney function, and hemoglobin A1c.

TAKEAWAY:

• Those receiving islets along with the kidney transplant had a 53% lower risk of graft failure, compared with the kidney-alone group.
• Those receiving islet transplantation had a significantly higher estimated life expectancy during 10-year follow-up (9.61 vs. 8.85 years).
• At 1 year post islet transplant, there was an estimated 89.4% probability of graft survival and a 70.2% probability of achieving independence from insulin.

IN PRACTICE:

“Although islet transplantation has previously been shown to improve glycemic control, compared with conventional insulin therapy in recent clinical trials, little was known about its long-term impact on patient prognosis until now. ... These results are exciting and provide hope for people living with type 1 diabetes and kidney transplants.”

SOURCE:

Presented Sept. 17, 2023, at the European Society for Organ Transplantation (ESOT) Congress 2023 by Mehdi Maanaoui, MD, a nephrologist at the University of Lille (France).

LIMITATIONS:

Observational, potential for residual confounding.

DISCLOSURES:

Dr. Maanaoui reports no relevant financial relationships.

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

TOPLINE:

Patients with type 1 diabetes who received transplanted islets along with a kidney transplant had significantly reduced mortality and transplant failure risks, compared with those who received kidney alone and continued to use insulin.

METHODOLOGY:

• Study population was all patients with type 1 diabetes in France who received a kidney transplant between 2000 and 2017.
• Among 2,393 patients, 327 were eligible for islet transplantation, including 47 who were actually transplanted with islets.
• The subjects were matched for factors including year of transplantation, recipient age, kidney function, and hemoglobin A1c.

TAKEAWAY:

• Those receiving islets along with the kidney transplant had a 53% lower risk of graft failure, compared with the kidney-alone group.
• Those receiving islet transplantation had a significantly higher estimated life expectancy during 10-year follow-up (9.61 vs. 8.85 years).
• At 1 year post islet transplant, there was an estimated 89.4% probability of graft survival and a 70.2% probability of achieving independence from insulin.

IN PRACTICE:

“Although islet transplantation has previously been shown to improve glycemic control, compared with conventional insulin therapy in recent clinical trials, little was known about its long-term impact on patient prognosis until now. ... These results are exciting and provide hope for people living with type 1 diabetes and kidney transplants.”

SOURCE:

Presented Sept. 17, 2023, at the European Society for Organ Transplantation (ESOT) Congress 2023 by Mehdi Maanaoui, MD, a nephrologist at the University of Lille (France).

LIMITATIONS:

Observational, potential for residual confounding.

DISCLOSURES:

Dr. Maanaoui reports no relevant financial relationships.

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

TOPLINE:

Patients with type 1 diabetes who received transplanted islets along with a kidney transplant had significantly reduced mortality and transplant failure risks, compared with those who received kidney alone and continued to use insulin.

METHODOLOGY:

• Study population was all patients with type 1 diabetes in France who received a kidney transplant between 2000 and 2017.
• Among 2,393 patients, 327 were eligible for islet transplantation, including 47 who were actually transplanted with islets.
• The subjects were matched for factors including year of transplantation, recipient age, kidney function, and hemoglobin A1c.

TAKEAWAY:

• Those receiving islets along with the kidney transplant had a 53% lower risk of graft failure, compared with the kidney-alone group.
• Those receiving islet transplantation had a significantly higher estimated life expectancy during 10-year follow-up (9.61 vs. 8.85 years).
• At 1 year post islet transplant, there was an estimated 89.4% probability of graft survival and a 70.2% probability of achieving independence from insulin.

IN PRACTICE:

“Although islet transplantation has previously been shown to improve glycemic control, compared with conventional insulin therapy in recent clinical trials, little was known about its long-term impact on patient prognosis until now. ... These results are exciting and provide hope for people living with type 1 diabetes and kidney transplants.”

SOURCE:

Presented Sept. 17, 2023, at the European Society for Organ Transplantation (ESOT) Congress 2023 by Mehdi Maanaoui, MD, a nephrologist at the University of Lille (France).

LIMITATIONS:

Observational, potential for residual confounding.

DISCLOSURES:

Dr. Maanaoui reports no relevant financial relationships.

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

Investigational muvalaplin (Eli Lilly), the first oral therapy being developed to lower lipoprotein (a) levels, was shown to reduce levels in a phase 1 trial, with no safety concerns, researchers report.

In a separate phase 2 study, olpasiran (Amgen), which is given by injection, lowered Lp(a) levels for nearly 1 year after the last dose, also without safety concerns, in a phase 2 trial extension.

Researchers presented these findings in two late breaking science sessions at the recent annual congress of the European Society of Cardiology. The muvalaplin trial was also simultaneously published online as a preliminary communication in JAMA.
 

Phase 1 trial of muvalaplin

Epidemiologic and genetic evidence suggests that Lp(a) has a causal role in cardiovascular disease (CVD) events, Stephen J. Nicholls, MBBS, PhD, and colleagues wrote.

In initial studies, Lp(a) was reduced by approximately 80% with an antisense oligonucleotide (pelacarsen, Ionis) and by up to 98% with RNA interference (olpasiran) – both injectable therapies.

Muvalaplin is a small molecule that disrupts the binding of apolipoprotein(a) to apo B100 that forms Lp(a), said Dr. Nicholls, from Monash University and Victoria Heart Institute, both in Melbourne.

In this first-in-human, phase 1 trial in 114 healthy individuals, Lp(a) levels were reduced up to 65% following daily administration of 100-800 mg of muvalaplin for 14 days, without safety or tolerability concerns or significant effects on plasminogen, a homologous protein, he said in an interview.

Approximately 20% of the population have high LP(a) levels, Dr. Nicholls noted.

“We saw in the PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor trials that Lp(a) lowering is associated with benefit, but those agents substantially lower LDL cholesterol,” he said. “Now, here for the first time we have an oral agent” that lowers Lp(a) levels. However, “we will still need to determine if this leads to a reduction in cardiovascular risk,” in longer and larger trials.

The researchers randomly assigned healthy adults aged 18-69 with a BMI of 30 kg/m² or less, into two groups.

The 55 participants in the single ascending dose group were randomly assigned to receive muvalaplin (1 mg, 10 mg, 30 mg, 100 mg, 200 mg, 400 mg, or 800 mg) or matching placebo daily for 14 days. They had a mean age of 29 years; 64% were female and 91% were White. Their median Lp(a) level was 10.3 mg/dL.

The 59 participants in the multiple ascending dose group, who were required to have Lp(a) of at least 30 mg/dL, were randomly assigned to receive muvalaplin (30 mg, 100 mg, 300 mg, 500 mg, or 800 mg) or placebo daily for 14 days. They had a mean age of 32; 58% were female and 80% were White. Their median Lp(a) level was 58.4 mg/dL.

The maximum placebo-adjusted Lp(a) reduction was 63% to 65%, which occurred on days 14 and 15, in participants who received doses of at least 100 mg.

The levels returned to baseline by day 29 for the 30-mg dose, day 43 for the 100-mg dose, and day 64 for the 300- to 800-mg doses. 

There were no deaths or serious adverse events. Treatment-associated adverse events were reported by 62% in the single ascending dose group and by 80% in the multiple ascending dose group; these were mild and transient and included headache, fatigue, and vomiting.  

Muvalaplin had no significant effects on LDL cholesterol, HDL cholesterol, or total cholesterol or apo B100, and did not significantly affect plasminogen levels or activity.

The team is currently conducting the phase 2 KRAKEN trial. They plan to enroll 233 patients aged 40 and older with elevated Lp(a) levels (≥ 175 nmol/L) and high risk for cardiovascular events. The primary outcome is change in Lp(a) levels at 12 weeks, and the estimated primary trial completion is this coming January.
 

OCEAN (a)-DOSE extended study of olpasiran

In a separate presentation, Michelle L. O’Donoghue, MD, MPH, reported findings from an extension of the phase 2 trial of olpasiran in patients with atherosclerotic CVD and elevated Lp(a).

courtesy Brigham and Women&#039;s Hospital

Olpasiran is a small interfering RNA (siRNA) molecule directed to the liver that prevents the assembly of Lp(a).

Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School in Boston, presented the main results from the OCEAN(a) DOSE (TIMI 67) study of olpasiran, at the 2022 annual scientific sessions of the American Heart Association, and the trial was simultaneously published online in the New England Journal of Medicine.

The trial included 281 patients with established atherosclerotic CVD and Lp(a) greater than 150 nmol/L (60 mg/dL). Participants were randomly assigned to one of four doses of olpasiran (10 mg, 75 mg, or 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously.

At 36 weeks, doses of 75 mg or more of olpasiran every 12 weeks led to reductions of more than 95% in levels of Lp(a).

The extension study aimed to examine the effects of olpasiran on levels of the oxidized phospholipids on apolipoprotein B100 (OxPL-apoB) and on levels of Lp(a), as well as safety, after the last administered dose.

The minimum extended off-treatment period was 72 weeks from randomization (in 276 patients). Complete follow-up was a median of 86 weeks (50 weeks after the last administered dose).

The study showed that “olpasiran is an siRNA that robustly lowers Lp(a) levels” and “leads to a marked and durable reduction” in proatherogenic OxPL-apoB, Dr. O’Donoghue reported.

Patients on doses of at least 75 mg every 12 weeks “sustained around a 40%-50% placebo-adjusted reduction in Lp(a) levels close to 1 year after the last dose.”

The long-term clinical efficacy and safety of olpasiran are being further evaluated in the ongoing phase 3 OCEAN(a)-Outcomes trial which has as an estimated enrollment of 6000 and projected completion in December 2026.

These are “exciting” results, and “we’re all waiting with bated breath for more news,” said session cochairperson Louise Bowman, MD, University of Oxford (England).

In reply to questions from the audience, Dr. O’Donoghue said that the only adverse events that were imbalanced during the on-treatment phase were injection-site reactions and localized hypersensitivity reactions, which were not reported during the off-treatment period. There was also no evidence of a proinflammatory increase in phospholipids, or of a rebound effect on Lp(a) levels after stopping olpasiran.

The muvalaplin study was funded by Eli Lilly. Dr. Nicholls reported numerous conflicts of interest with various pharmaceutical companies. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Merck, and Novartis; consulting with Amgen and Novartis; and serving as a data and safety monitor for AstraZeneca and Janssen.

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

Investigational muvalaplin (Eli Lilly), the first oral therapy being developed to lower lipoprotein (a) levels, was shown to reduce levels in a phase 1 trial, with no safety concerns, researchers report.

In a separate phase 2 study, olpasiran (Amgen), which is given by injection, lowered Lp(a) levels for nearly 1 year after the last dose, also without safety concerns, in a phase 2 trial extension.

Researchers presented these findings in two late breaking science sessions at the recent annual congress of the European Society of Cardiology. The muvalaplin trial was also simultaneously published online as a preliminary communication in JAMA.
 

Phase 1 trial of muvalaplin

Epidemiologic and genetic evidence suggests that Lp(a) has a causal role in cardiovascular disease (CVD) events, Stephen J. Nicholls, MBBS, PhD, and colleagues wrote.

In initial studies, Lp(a) was reduced by approximately 80% with an antisense oligonucleotide (pelacarsen, Ionis) and by up to 98% with RNA interference (olpasiran) – both injectable therapies.

Muvalaplin is a small molecule that disrupts the binding of apolipoprotein(a) to apo B100 that forms Lp(a), said Dr. Nicholls, from Monash University and Victoria Heart Institute, both in Melbourne.

In this first-in-human, phase 1 trial in 114 healthy individuals, Lp(a) levels were reduced up to 65% following daily administration of 100-800 mg of muvalaplin for 14 days, without safety or tolerability concerns or significant effects on plasminogen, a homologous protein, he said in an interview.

Approximately 20% of the population have high LP(a) levels, Dr. Nicholls noted.

“We saw in the PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor trials that Lp(a) lowering is associated with benefit, but those agents substantially lower LDL cholesterol,” he said. “Now, here for the first time we have an oral agent” that lowers Lp(a) levels. However, “we will still need to determine if this leads to a reduction in cardiovascular risk,” in longer and larger trials.

The researchers randomly assigned healthy adults aged 18-69 with a BMI of 30 kg/m² or less, into two groups.

The 55 participants in the single ascending dose group were randomly assigned to receive muvalaplin (1 mg, 10 mg, 30 mg, 100 mg, 200 mg, 400 mg, or 800 mg) or matching placebo daily for 14 days. They had a mean age of 29 years; 64% were female and 91% were White. Their median Lp(a) level was 10.3 mg/dL.

The 59 participants in the multiple ascending dose group, who were required to have Lp(a) of at least 30 mg/dL, were randomly assigned to receive muvalaplin (30 mg, 100 mg, 300 mg, 500 mg, or 800 mg) or placebo daily for 14 days. They had a mean age of 32; 58% were female and 80% were White. Their median Lp(a) level was 58.4 mg/dL.

The maximum placebo-adjusted Lp(a) reduction was 63% to 65%, which occurred on days 14 and 15, in participants who received doses of at least 100 mg.

The levels returned to baseline by day 29 for the 30-mg dose, day 43 for the 100-mg dose, and day 64 for the 300- to 800-mg doses. 

There were no deaths or serious adverse events. Treatment-associated adverse events were reported by 62% in the single ascending dose group and by 80% in the multiple ascending dose group; these were mild and transient and included headache, fatigue, and vomiting.  

Muvalaplin had no significant effects on LDL cholesterol, HDL cholesterol, or total cholesterol or apo B100, and did not significantly affect plasminogen levels or activity.

The team is currently conducting the phase 2 KRAKEN trial. They plan to enroll 233 patients aged 40 and older with elevated Lp(a) levels (≥ 175 nmol/L) and high risk for cardiovascular events. The primary outcome is change in Lp(a) levels at 12 weeks, and the estimated primary trial completion is this coming January.
 

OCEAN (a)-DOSE extended study of olpasiran

In a separate presentation, Michelle L. O’Donoghue, MD, MPH, reported findings from an extension of the phase 2 trial of olpasiran in patients with atherosclerotic CVD and elevated Lp(a).

courtesy Brigham and Women&#039;s Hospital

Olpasiran is a small interfering RNA (siRNA) molecule directed to the liver that prevents the assembly of Lp(a).

Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School in Boston, presented the main results from the OCEAN(a) DOSE (TIMI 67) study of olpasiran, at the 2022 annual scientific sessions of the American Heart Association, and the trial was simultaneously published online in the New England Journal of Medicine.

The trial included 281 patients with established atherosclerotic CVD and Lp(a) greater than 150 nmol/L (60 mg/dL). Participants were randomly assigned to one of four doses of olpasiran (10 mg, 75 mg, or 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously.

At 36 weeks, doses of 75 mg or more of olpasiran every 12 weeks led to reductions of more than 95% in levels of Lp(a).

The extension study aimed to examine the effects of olpasiran on levels of the oxidized phospholipids on apolipoprotein B100 (OxPL-apoB) and on levels of Lp(a), as well as safety, after the last administered dose.

The minimum extended off-treatment period was 72 weeks from randomization (in 276 patients). Complete follow-up was a median of 86 weeks (50 weeks after the last administered dose).

The study showed that “olpasiran is an siRNA that robustly lowers Lp(a) levels” and “leads to a marked and durable reduction” in proatherogenic OxPL-apoB, Dr. O’Donoghue reported.

Patients on doses of at least 75 mg every 12 weeks “sustained around a 40%-50% placebo-adjusted reduction in Lp(a) levels close to 1 year after the last dose.”

The long-term clinical efficacy and safety of olpasiran are being further evaluated in the ongoing phase 3 OCEAN(a)-Outcomes trial which has as an estimated enrollment of 6000 and projected completion in December 2026.

These are “exciting” results, and “we’re all waiting with bated breath for more news,” said session cochairperson Louise Bowman, MD, University of Oxford (England).

In reply to questions from the audience, Dr. O’Donoghue said that the only adverse events that were imbalanced during the on-treatment phase were injection-site reactions and localized hypersensitivity reactions, which were not reported during the off-treatment period. There was also no evidence of a proinflammatory increase in phospholipids, or of a rebound effect on Lp(a) levels after stopping olpasiran.

The muvalaplin study was funded by Eli Lilly. Dr. Nicholls reported numerous conflicts of interest with various pharmaceutical companies. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Merck, and Novartis; consulting with Amgen and Novartis; and serving as a data and safety monitor for AstraZeneca and Janssen.

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

Investigational muvalaplin (Eli Lilly), the first oral therapy being developed to lower lipoprotein (a) levels, was shown to reduce levels in a phase 1 trial, with no safety concerns, researchers report.

In a separate phase 2 study, olpasiran (Amgen), which is given by injection, lowered Lp(a) levels for nearly 1 year after the last dose, also without safety concerns, in a phase 2 trial extension.

Researchers presented these findings in two late breaking science sessions at the recent annual congress of the European Society of Cardiology. The muvalaplin trial was also simultaneously published online as a preliminary communication in JAMA.
 

Phase 1 trial of muvalaplin

Epidemiologic and genetic evidence suggests that Lp(a) has a causal role in cardiovascular disease (CVD) events, Stephen J. Nicholls, MBBS, PhD, and colleagues wrote.

In initial studies, Lp(a) was reduced by approximately 80% with an antisense oligonucleotide (pelacarsen, Ionis) and by up to 98% with RNA interference (olpasiran) – both injectable therapies.

Muvalaplin is a small molecule that disrupts the binding of apolipoprotein(a) to apo B100 that forms Lp(a), said Dr. Nicholls, from Monash University and Victoria Heart Institute, both in Melbourne.

In this first-in-human, phase 1 trial in 114 healthy individuals, Lp(a) levels were reduced up to 65% following daily administration of 100-800 mg of muvalaplin for 14 days, without safety or tolerability concerns or significant effects on plasminogen, a homologous protein, he said in an interview.

Approximately 20% of the population have high LP(a) levels, Dr. Nicholls noted.

“We saw in the PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor trials that Lp(a) lowering is associated with benefit, but those agents substantially lower LDL cholesterol,” he said. “Now, here for the first time we have an oral agent” that lowers Lp(a) levels. However, “we will still need to determine if this leads to a reduction in cardiovascular risk,” in longer and larger trials.

The researchers randomly assigned healthy adults aged 18-69 with a BMI of 30 kg/m² or less, into two groups.

The 55 participants in the single ascending dose group were randomly assigned to receive muvalaplin (1 mg, 10 mg, 30 mg, 100 mg, 200 mg, 400 mg, or 800 mg) or matching placebo daily for 14 days. They had a mean age of 29 years; 64% were female and 91% were White. Their median Lp(a) level was 10.3 mg/dL.

The 59 participants in the multiple ascending dose group, who were required to have Lp(a) of at least 30 mg/dL, were randomly assigned to receive muvalaplin (30 mg, 100 mg, 300 mg, 500 mg, or 800 mg) or placebo daily for 14 days. They had a mean age of 32; 58% were female and 80% were White. Their median Lp(a) level was 58.4 mg/dL.

The maximum placebo-adjusted Lp(a) reduction was 63% to 65%, which occurred on days 14 and 15, in participants who received doses of at least 100 mg.

The levels returned to baseline by day 29 for the 30-mg dose, day 43 for the 100-mg dose, and day 64 for the 300- to 800-mg doses. 

There were no deaths or serious adverse events. Treatment-associated adverse events were reported by 62% in the single ascending dose group and by 80% in the multiple ascending dose group; these were mild and transient and included headache, fatigue, and vomiting.  

Muvalaplin had no significant effects on LDL cholesterol, HDL cholesterol, or total cholesterol or apo B100, and did not significantly affect plasminogen levels or activity.

The team is currently conducting the phase 2 KRAKEN trial. They plan to enroll 233 patients aged 40 and older with elevated Lp(a) levels (≥ 175 nmol/L) and high risk for cardiovascular events. The primary outcome is change in Lp(a) levels at 12 weeks, and the estimated primary trial completion is this coming January.
 

OCEAN (a)-DOSE extended study of olpasiran

In a separate presentation, Michelle L. O’Donoghue, MD, MPH, reported findings from an extension of the phase 2 trial of olpasiran in patients with atherosclerotic CVD and elevated Lp(a).

courtesy Brigham and Women&#039;s Hospital

Olpasiran is a small interfering RNA (siRNA) molecule directed to the liver that prevents the assembly of Lp(a).

Dr. O’Donoghue, from Brigham and Women’s Hospital and Harvard Medical School in Boston, presented the main results from the OCEAN(a) DOSE (TIMI 67) study of olpasiran, at the 2022 annual scientific sessions of the American Heart Association, and the trial was simultaneously published online in the New England Journal of Medicine.

The trial included 281 patients with established atherosclerotic CVD and Lp(a) greater than 150 nmol/L (60 mg/dL). Participants were randomly assigned to one of four doses of olpasiran (10 mg, 75 mg, or 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously.

At 36 weeks, doses of 75 mg or more of olpasiran every 12 weeks led to reductions of more than 95% in levels of Lp(a).

The extension study aimed to examine the effects of olpasiran on levels of the oxidized phospholipids on apolipoprotein B100 (OxPL-apoB) and on levels of Lp(a), as well as safety, after the last administered dose.

The minimum extended off-treatment period was 72 weeks from randomization (in 276 patients). Complete follow-up was a median of 86 weeks (50 weeks after the last administered dose).

The study showed that “olpasiran is an siRNA that robustly lowers Lp(a) levels” and “leads to a marked and durable reduction” in proatherogenic OxPL-apoB, Dr. O’Donoghue reported.

Patients on doses of at least 75 mg every 12 weeks “sustained around a 40%-50% placebo-adjusted reduction in Lp(a) levels close to 1 year after the last dose.”

The long-term clinical efficacy and safety of olpasiran are being further evaluated in the ongoing phase 3 OCEAN(a)-Outcomes trial which has as an estimated enrollment of 6000 and projected completion in December 2026.

These are “exciting” results, and “we’re all waiting with bated breath for more news,” said session cochairperson Louise Bowman, MD, University of Oxford (England).

In reply to questions from the audience, Dr. O’Donoghue said that the only adverse events that were imbalanced during the on-treatment phase were injection-site reactions and localized hypersensitivity reactions, which were not reported during the off-treatment period. There was also no evidence of a proinflammatory increase in phospholipids, or of a rebound effect on Lp(a) levels after stopping olpasiran.

The muvalaplin study was funded by Eli Lilly. Dr. Nicholls reported numerous conflicts of interest with various pharmaceutical companies. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Merck, and Novartis; consulting with Amgen and Novartis; and serving as a data and safety monitor for AstraZeneca and Janssen.

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

A newly published scientific statement from the American Heart Association focuses on the impact of aggressive low-density lipoprotein cholesterol (LDL-C) lowering on the risk for dementia and hemorrhagic stroke.

“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.

The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.

The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.

They reached four main conclusions:

• First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
• Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
• Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
• Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.

The research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article appeared on Medscape.com.

A newly published scientific statement from the American Heart Association focuses on the impact of aggressive low-density lipoprotein cholesterol (LDL-C) lowering on the risk for dementia and hemorrhagic stroke.

“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.

The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.

The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.

They reached four main conclusions:

• First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
• Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
• Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
• Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.

The research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article appeared on Medscape.com.

A newly published scientific statement from the American Heart Association focuses on the impact of aggressive low-density lipoprotein cholesterol (LDL-C) lowering on the risk for dementia and hemorrhagic stroke.

“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.

The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.

The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.

They reached four main conclusions:

• First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
• Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
• Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
• Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.

The research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article appeared on Medscape.com.

A radiologist who claims he was forced to resign after requesting to work from home has settled his discrimination lawsuit with a New York hospital.

Although the case was resolved without a definitive win, legal analysts say the complaint raises important questions about whether some physicians have the right to work from home.

Since the pandemic, employers across the country have become more accepting of professionals working remotely. But are some doctors legally entitled to the accommodation? And if so, how do physicians prove the allowance is reasonable for their circumstances?

Richard Heiden, MD, sued New York City Health and Hospitals in 2020, claiming discrimination and retaliation violations under the American with Disabilities Act (ADA) and the New York State Human Rights Law. Dr. Heiden, who has ulcerative colitis, had asked to work off-site during the start of the pandemic, but the hospital denied his accommodation request. Shortly later, administrators accused Dr. Heiden of poor performance and requested he resign or administrators would terminate him, according to his lawsuit.

Attorneys for New York City Health and Hospitals contended that Dr. Heiden was a poorly performing radiologist who was undergoing a performance review at the time of his accommodation request. The radiologist’s departure was related to the results of the review and had nothing to do with his disability or accommodation request, according to the hospital.

The undisclosed settlement ends a 3-year court battle between Dr. Heiden and the hospital corporation.

In an email, Laura Williams, an attorney for the hospital corporation, said that “the settlement was in the best interest of all parties.”

Dr. Heiden and his attorneys also did not respond to requests for comment.

A critical piece to the puzzle is understanding who is protected under the ADA and is therefore entitled to reasonable accommodations, said Doron Dorfman, JSD, an associate professor at Seton Hall University Law School in Newark, N.J., who focuses on disability law.

A common misconception is that only physicians with a physical disability are “disabled,” he said. However, under the law, a disabled individual is anyone with a physical or mental impairment – including mental illness – that limits major life activities; a person with a history of such impairment; or a person who is perceived by others as having an impairment.

“The law is much broader than many people think,” he said. “I think a lot of people don’t think about those with invisible disabilities, such as people with allergies, those who are immunocompromised, those with chronic illnesses. A lot of people don’t see themselves as disabled, and a lot of employers don’t see them as disabled.”

Working from home has not historically been considered a “reasonable accommodation” under the ADA, Mr. Dorfman said. However, that appears to be changing.

“There has been a sea change,” Mr. Dorfman said. “The question is coming before the courts more frequently, and recent legal decisions show judges may be altering their views on the subject.”
 

What led to the doctor’s lawsuit?

Dr. Heiden, a longtime radiologist, had practiced at Lincoln Medical and Mental Health Center for about a year when he requested to work remotely. (Lincoln is operated by New York City Health and Hospitals.) At the time, the governor of New York had ordered a statewide lockdown because of COVID-19, and Dr. Heiden expressed concern that his ulcerative colitis made him a high-risk individual for the virus, according to court documents.

In his March 22, 2020, request, Dr. Heiden said that, except for fluoroscopy, his job could be done entirely from his home, according to a district court summary of the case. He also offered to pay for any costs associated with the remote work setup.

Around the same time, New York City Health and Hospitals permitted its facilities to issue a limited number of workstations to radiologists to facilitate remote work in the event of COVID-related staffing shortages. Administrators were in the process of acquiring remote radiology workstations and determining which radiologists at Lincoln would receive them, according to the case summary.

On March 24, the chair of radiology at Lincoln met with Dr. Heiden to review the results of a recent focused professional practice evaluation (FPPE). An FPPE refers to an intensive review of an expansive selection of patient cases handled by the subject physician. During the meeting, the chair that claimed Dr. Heiden was a poor performer and was accurate in his assessments 93.8% of the time, which was below the hospital’s 97% threshold, according to Dr. Heiden’s lawsuit. Dr. Heiden disagreed with the results, and the two engaged in several more meetings.

Meanwhile, Dr. Heiden’s accommodation request was forwarded to other administrators. In an email introduced into court evidence, the chair indicated he did not support the accommodation, writing that Dr. Heiden’s “skill set does not meet the criteria for the initial installations” of the workstations.

On March 26, 2020, the chair allegedly asked Dr. Heiden to either resign or he would be terminated and reported to the New York State Office of Professional Medical Conduct. Four days later, Dr. Heiden learned that his accommodation request had been denied. He resigned on April 2, 2020.

In his lawsuit, Dr. Heiden claimed that the hospital discriminated against him on the basis of his disability in violation of ADA by denying him equal terms and conditions of employment and failing to provide a reasonable accommodation.

The defendants, who included the radiology chair, did not dispute that Dr. Heiden was asked to resign or that administrators warned termination, but they argued the impetus was his FPPE results and a history of inaccurate interpretations. Other clinicians and physicians had expressed concerns about Dr. Heiden’s “lack of clarity [and] interpretive errors,” according to deposition testimony. The hospital emphasized the FPPE had concluded before Dr. Heiden’s accommodation request was made.

New York City Health and Hospitals requested a federal judge dismiss the lawsuit for lack of valid claims. In January 2023, U.S. District Judge Lewis Liman allowed the case to proceed, ruling that some of Dr. Heiden’s claims had merit.

“Plaintiff has satisfied his obligation to proffer sufficient evidence to create an inference of retaliatory or discriminatory intent,” Judge Liman wrote in his decision. “[The chair] had not always planned to ask for plaintiff’s resignation based on the results of the FPPE completed on March 10, 2020. The decision to ask for that resignation arose shortly after the request for the accommodation. And there is evidence from which the jury could find that [the chair] was not receptive to making the accommodation.”

A jury trial was scheduled for July 2023, but the parties reached a settlement on May 31, 2023.
 

Is working from home reasonable for physicians?

The widespread swing to remote work in recent years has paved a smoother road for physicians who request the accommodation, said Peter Poullos, MD, clinical associate professor of radiology, gastroenterology, and hepatology at Stanford (Calif.) University and founder and cochair of the Stanford Medicine Alliance for Disability Inclusion and Equity.

“There is now a precedent and examples all over that working from home for some is a viable alternative to working in the hospital or a clinic,” Dr. Poullos said. “If a lawyer can point to instances of other people having received the same accommodation, even if the accommodation was given to someone without a disability, it’s much harder for an employer to say: ‘It’s not possible.’ Because clearly, it is.”

A key factor is the employee’s job duties and whether the employee can complete them remotely, said Mr. Dorfman. With physicians, the reasonableness would heavily depend on their specialty.

A radiologist, for example, would probably have a stronger case for performing their duties remotely compared with a surgeon, Dr. Poullos said.

In general, whether an accommodation is reasonable is decided on a case-by-case basis and usually includes reviewing supporting documentation from a medical provider, said Emily Harvey, a Denver-based disability law attorney. Employers are allowed to deny accommodations if they would cause an undue burden to the employer or fundamentally alter the nature or operation of the job or business.

“When it comes to the ADA, and disability rights in general, the analysis is based on the need of the individual,” she said. “Two people with identical diagnoses could need vastly different accommodations to be successful in the same job.”

Mr. Dorfman added that employers are only required to provide an accommodation that is reasonable under the circumstances, whether or not that accommodation meets the preferred request of the employee. For instance, if an immunocompromised physician asked to work from home, but the employer could ensure that all those working around the physician will mask, that could be reasonable enough.

A recent case analysis by Bloomberg Law shows that more courts are siding with employees who request remote work, compared with in past years. Employees who made disability-related remote work requests prevailed in 40% of federal court rulings from 2021 to 2023 versusa success rate of 30% from 2017 to 2019, according to the July 2023 analysis.

The analysis shows that employers still win the majority of the time, but that the gap is closing, Mr. Dorfman said.

In a September 2020 decision, for example, a Massachusetts District Court ruled in favor of an employee with asthma who was precluding from working at home by a behavioral and mental health agency. U.S. Magistrate Judge Katherine Robertson said that the manager was entitled to telework as a reasonable accommodation under the ADA for 60 days or until further notice. The lawsuit was settled in 2021.

“I think judges are much more used to working from home themselves,” Mr. Dorfman said. “That may affect their sense of accepting remote work as a reasonable accommodation. Their personal experience with it [may] actually inform their view of the topic.”
 

Your accommodation request was denied: Now what?

If you are unsure about your rights under the ADA, a first step is understanding the law’s protections and learning the obligations of your employer. 

Keep in mind that not everyone at your workplace may understand the law and what is required, said Dr. Poullos. When making a request to work from home, ensure that you’re using the right words and asking the right people, he advised. Some physicians, for instance, may only discuss the request with their direct supervisor and give up when the request is denied. “The employee might say, ‘I’ve been dealing with some medical issues and I’m really tired and need to adjust my schedule.’ They don’t mention the word ‘disability,’ they don’t mention the ADA, they don’t mention the word ‘accommodation,’ and so that might not trigger the appropriate response.”

Lisa Meeks, PhD, an expert and researcher in disabilities in medical education, encourages physicians and others to follow the appeals process at their institution if they feel their accommodation request has been unjustly denied.

Research shows that physicians who make accommodation requests rarely escalate denials to an appeal, grievance, or complaint, said Dr. Meeks, cohost of the Docs With Disabilities podcast and director of the Docs With Disabilities Initiative. The initiative aims to use research, education, and stories to drive change in perceptions, disability policy, and procedures in health professions and in biomedical and science education.

If an accommodation cannot be agreed on, doctors can reach out the Equal Employment Opportunity Commission and file a discrimination charge. The agency will review the case and provide an opinion on whether the charge has merit. The EEOC’s decision is not binding in court, and even if the agency believes the charge has no merit, employees still have the right to sue, he said.

Ms. Harvey added that the EEOC has many resources on its website, and that most states also have civil rights agencies that have additional resources. Every state and U.S. territory also has a protection and advocacy organization that may be able to help. Physicians can also review their state bar to locate and consult with disability rights attorneys.

Although it may seem like an uphill battle to push for an accommodation, it can be worth it in the end, said Michael Argenyi, MD, an addiction medicine specialist and assistant professor at the University of Massachusetts, Worcester. Dr. Argenyi, who has hearing loss, was featured on the Docs With Disabilities podcast.

“It’s difficult to ‘rock the boat’ and ask for support from the C-suite for employees with disabilities, or to rearrange a small medical office budget to establish a byline just for accommodations,” Dr. Argenyi said. “Yet, the payoff is worthwhile – patients and fellow colleagues notice commitments to diversity building and inclusion.”

A version of this article appeared on Medscape.com.

A radiologist who claims he was forced to resign after requesting to work from home has settled his discrimination lawsuit with a New York hospital.

Although the case was resolved without a definitive win, legal analysts say the complaint raises important questions about whether some physicians have the right to work from home.

Since the pandemic, employers across the country have become more accepting of professionals working remotely. But are some doctors legally entitled to the accommodation? And if so, how do physicians prove the allowance is reasonable for their circumstances?

Richard Heiden, MD, sued New York City Health and Hospitals in 2020, claiming discrimination and retaliation violations under the American with Disabilities Act (ADA) and the New York State Human Rights Law. Dr. Heiden, who has ulcerative colitis, had asked to work off-site during the start of the pandemic, but the hospital denied his accommodation request. Shortly later, administrators accused Dr. Heiden of poor performance and requested he resign or administrators would terminate him, according to his lawsuit.

Attorneys for New York City Health and Hospitals contended that Dr. Heiden was a poorly performing radiologist who was undergoing a performance review at the time of his accommodation request. The radiologist’s departure was related to the results of the review and had nothing to do with his disability or accommodation request, according to the hospital.

The undisclosed settlement ends a 3-year court battle between Dr. Heiden and the hospital corporation.

In an email, Laura Williams, an attorney for the hospital corporation, said that “the settlement was in the best interest of all parties.”

Dr. Heiden and his attorneys also did not respond to requests for comment.

A critical piece to the puzzle is understanding who is protected under the ADA and is therefore entitled to reasonable accommodations, said Doron Dorfman, JSD, an associate professor at Seton Hall University Law School in Newark, N.J., who focuses on disability law.

A common misconception is that only physicians with a physical disability are “disabled,” he said. However, under the law, a disabled individual is anyone with a physical or mental impairment – including mental illness – that limits major life activities; a person with a history of such impairment; or a person who is perceived by others as having an impairment.

“The law is much broader than many people think,” he said. “I think a lot of people don’t think about those with invisible disabilities, such as people with allergies, those who are immunocompromised, those with chronic illnesses. A lot of people don’t see themselves as disabled, and a lot of employers don’t see them as disabled.”

Working from home has not historically been considered a “reasonable accommodation” under the ADA, Mr. Dorfman said. However, that appears to be changing.

“There has been a sea change,” Mr. Dorfman said. “The question is coming before the courts more frequently, and recent legal decisions show judges may be altering their views on the subject.”
 

What led to the doctor’s lawsuit?

Dr. Heiden, a longtime radiologist, had practiced at Lincoln Medical and Mental Health Center for about a year when he requested to work remotely. (Lincoln is operated by New York City Health and Hospitals.) At the time, the governor of New York had ordered a statewide lockdown because of COVID-19, and Dr. Heiden expressed concern that his ulcerative colitis made him a high-risk individual for the virus, according to court documents.

In his March 22, 2020, request, Dr. Heiden said that, except for fluoroscopy, his job could be done entirely from his home, according to a district court summary of the case. He also offered to pay for any costs associated with the remote work setup.

Around the same time, New York City Health and Hospitals permitted its facilities to issue a limited number of workstations to radiologists to facilitate remote work in the event of COVID-related staffing shortages. Administrators were in the process of acquiring remote radiology workstations and determining which radiologists at Lincoln would receive them, according to the case summary.

On March 24, the chair of radiology at Lincoln met with Dr. Heiden to review the results of a recent focused professional practice evaluation (FPPE). An FPPE refers to an intensive review of an expansive selection of patient cases handled by the subject physician. During the meeting, the chair that claimed Dr. Heiden was a poor performer and was accurate in his assessments 93.8% of the time, which was below the hospital’s 97% threshold, according to Dr. Heiden’s lawsuit. Dr. Heiden disagreed with the results, and the two engaged in several more meetings.

Meanwhile, Dr. Heiden’s accommodation request was forwarded to other administrators. In an email introduced into court evidence, the chair indicated he did not support the accommodation, writing that Dr. Heiden’s “skill set does not meet the criteria for the initial installations” of the workstations.

On March 26, 2020, the chair allegedly asked Dr. Heiden to either resign or he would be terminated and reported to the New York State Office of Professional Medical Conduct. Four days later, Dr. Heiden learned that his accommodation request had been denied. He resigned on April 2, 2020.

In his lawsuit, Dr. Heiden claimed that the hospital discriminated against him on the basis of his disability in violation of ADA by denying him equal terms and conditions of employment and failing to provide a reasonable accommodation.

The defendants, who included the radiology chair, did not dispute that Dr. Heiden was asked to resign or that administrators warned termination, but they argued the impetus was his FPPE results and a history of inaccurate interpretations. Other clinicians and physicians had expressed concerns about Dr. Heiden’s “lack of clarity [and] interpretive errors,” according to deposition testimony. The hospital emphasized the FPPE had concluded before Dr. Heiden’s accommodation request was made.

New York City Health and Hospitals requested a federal judge dismiss the lawsuit for lack of valid claims. In January 2023, U.S. District Judge Lewis Liman allowed the case to proceed, ruling that some of Dr. Heiden’s claims had merit.

“Plaintiff has satisfied his obligation to proffer sufficient evidence to create an inference of retaliatory or discriminatory intent,” Judge Liman wrote in his decision. “[The chair] had not always planned to ask for plaintiff’s resignation based on the results of the FPPE completed on March 10, 2020. The decision to ask for that resignation arose shortly after the request for the accommodation. And there is evidence from which the jury could find that [the chair] was not receptive to making the accommodation.”

A jury trial was scheduled for July 2023, but the parties reached a settlement on May 31, 2023.
 

Is working from home reasonable for physicians?

The widespread swing to remote work in recent years has paved a smoother road for physicians who request the accommodation, said Peter Poullos, MD, clinical associate professor of radiology, gastroenterology, and hepatology at Stanford (Calif.) University and founder and cochair of the Stanford Medicine Alliance for Disability Inclusion and Equity.

“There is now a precedent and examples all over that working from home for some is a viable alternative to working in the hospital or a clinic,” Dr. Poullos said. “If a lawyer can point to instances of other people having received the same accommodation, even if the accommodation was given to someone without a disability, it’s much harder for an employer to say: ‘It’s not possible.’ Because clearly, it is.”

A key factor is the employee’s job duties and whether the employee can complete them remotely, said Mr. Dorfman. With physicians, the reasonableness would heavily depend on their specialty.

A radiologist, for example, would probably have a stronger case for performing their duties remotely compared with a surgeon, Dr. Poullos said.

In general, whether an accommodation is reasonable is decided on a case-by-case basis and usually includes reviewing supporting documentation from a medical provider, said Emily Harvey, a Denver-based disability law attorney. Employers are allowed to deny accommodations if they would cause an undue burden to the employer or fundamentally alter the nature or operation of the job or business.

“When it comes to the ADA, and disability rights in general, the analysis is based on the need of the individual,” she said. “Two people with identical diagnoses could need vastly different accommodations to be successful in the same job.”

Mr. Dorfman added that employers are only required to provide an accommodation that is reasonable under the circumstances, whether or not that accommodation meets the preferred request of the employee. For instance, if an immunocompromised physician asked to work from home, but the employer could ensure that all those working around the physician will mask, that could be reasonable enough.

A recent case analysis by Bloomberg Law shows that more courts are siding with employees who request remote work, compared with in past years. Employees who made disability-related remote work requests prevailed in 40% of federal court rulings from 2021 to 2023 versusa success rate of 30% from 2017 to 2019, according to the July 2023 analysis.

The analysis shows that employers still win the majority of the time, but that the gap is closing, Mr. Dorfman said.

In a September 2020 decision, for example, a Massachusetts District Court ruled in favor of an employee with asthma who was precluding from working at home by a behavioral and mental health agency. U.S. Magistrate Judge Katherine Robertson said that the manager was entitled to telework as a reasonable accommodation under the ADA for 60 days or until further notice. The lawsuit was settled in 2021.

“I think judges are much more used to working from home themselves,” Mr. Dorfman said. “That may affect their sense of accepting remote work as a reasonable accommodation. Their personal experience with it [may] actually inform their view of the topic.”
 

Your accommodation request was denied: Now what?

If you are unsure about your rights under the ADA, a first step is understanding the law’s protections and learning the obligations of your employer. 

Keep in mind that not everyone at your workplace may understand the law and what is required, said Dr. Poullos. When making a request to work from home, ensure that you’re using the right words and asking the right people, he advised. Some physicians, for instance, may only discuss the request with their direct supervisor and give up when the request is denied. “The employee might say, ‘I’ve been dealing with some medical issues and I’m really tired and need to adjust my schedule.’ They don’t mention the word ‘disability,’ they don’t mention the ADA, they don’t mention the word ‘accommodation,’ and so that might not trigger the appropriate response.”

Lisa Meeks, PhD, an expert and researcher in disabilities in medical education, encourages physicians and others to follow the appeals process at their institution if they feel their accommodation request has been unjustly denied.

Research shows that physicians who make accommodation requests rarely escalate denials to an appeal, grievance, or complaint, said Dr. Meeks, cohost of the Docs With Disabilities podcast and director of the Docs With Disabilities Initiative. The initiative aims to use research, education, and stories to drive change in perceptions, disability policy, and procedures in health professions and in biomedical and science education.

If an accommodation cannot be agreed on, doctors can reach out the Equal Employment Opportunity Commission and file a discrimination charge. The agency will review the case and provide an opinion on whether the charge has merit. The EEOC’s decision is not binding in court, and even if the agency believes the charge has no merit, employees still have the right to sue, he said.

Ms. Harvey added that the EEOC has many resources on its website, and that most states also have civil rights agencies that have additional resources. Every state and U.S. territory also has a protection and advocacy organization that may be able to help. Physicians can also review their state bar to locate and consult with disability rights attorneys.

Although it may seem like an uphill battle to push for an accommodation, it can be worth it in the end, said Michael Argenyi, MD, an addiction medicine specialist and assistant professor at the University of Massachusetts, Worcester. Dr. Argenyi, who has hearing loss, was featured on the Docs With Disabilities podcast.

“It’s difficult to ‘rock the boat’ and ask for support from the C-suite for employees with disabilities, or to rearrange a small medical office budget to establish a byline just for accommodations,” Dr. Argenyi said. “Yet, the payoff is worthwhile – patients and fellow colleagues notice commitments to diversity building and inclusion.”

A version of this article appeared on Medscape.com.

A radiologist who claims he was forced to resign after requesting to work from home has settled his discrimination lawsuit with a New York hospital.

Although the case was resolved without a definitive win, legal analysts say the complaint raises important questions about whether some physicians have the right to work from home.

Since the pandemic, employers across the country have become more accepting of professionals working remotely. But are some doctors legally entitled to the accommodation? And if so, how do physicians prove the allowance is reasonable for their circumstances?

Richard Heiden, MD, sued New York City Health and Hospitals in 2020, claiming discrimination and retaliation violations under the American with Disabilities Act (ADA) and the New York State Human Rights Law. Dr. Heiden, who has ulcerative colitis, had asked to work off-site during the start of the pandemic, but the hospital denied his accommodation request. Shortly later, administrators accused Dr. Heiden of poor performance and requested he resign or administrators would terminate him, according to his lawsuit.

Attorneys for New York City Health and Hospitals contended that Dr. Heiden was a poorly performing radiologist who was undergoing a performance review at the time of his accommodation request. The radiologist’s departure was related to the results of the review and had nothing to do with his disability or accommodation request, according to the hospital.

The undisclosed settlement ends a 3-year court battle between Dr. Heiden and the hospital corporation.

In an email, Laura Williams, an attorney for the hospital corporation, said that “the settlement was in the best interest of all parties.”

Dr. Heiden and his attorneys also did not respond to requests for comment.

A critical piece to the puzzle is understanding who is protected under the ADA and is therefore entitled to reasonable accommodations, said Doron Dorfman, JSD, an associate professor at Seton Hall University Law School in Newark, N.J., who focuses on disability law.

A common misconception is that only physicians with a physical disability are “disabled,” he said. However, under the law, a disabled individual is anyone with a physical or mental impairment – including mental illness – that limits major life activities; a person with a history of such impairment; or a person who is perceived by others as having an impairment.

“The law is much broader than many people think,” he said. “I think a lot of people don’t think about those with invisible disabilities, such as people with allergies, those who are immunocompromised, those with chronic illnesses. A lot of people don’t see themselves as disabled, and a lot of employers don’t see them as disabled.”

Working from home has not historically been considered a “reasonable accommodation” under the ADA, Mr. Dorfman said. However, that appears to be changing.

“There has been a sea change,” Mr. Dorfman said. “The question is coming before the courts more frequently, and recent legal decisions show judges may be altering their views on the subject.”
 

What led to the doctor’s lawsuit?

Dr. Heiden, a longtime radiologist, had practiced at Lincoln Medical and Mental Health Center for about a year when he requested to work remotely. (Lincoln is operated by New York City Health and Hospitals.) At the time, the governor of New York had ordered a statewide lockdown because of COVID-19, and Dr. Heiden expressed concern that his ulcerative colitis made him a high-risk individual for the virus, according to court documents.

In his March 22, 2020, request, Dr. Heiden said that, except for fluoroscopy, his job could be done entirely from his home, according to a district court summary of the case. He also offered to pay for any costs associated with the remote work setup.

Around the same time, New York City Health and Hospitals permitted its facilities to issue a limited number of workstations to radiologists to facilitate remote work in the event of COVID-related staffing shortages. Administrators were in the process of acquiring remote radiology workstations and determining which radiologists at Lincoln would receive them, according to the case summary.

On March 24, the chair of radiology at Lincoln met with Dr. Heiden to review the results of a recent focused professional practice evaluation (FPPE). An FPPE refers to an intensive review of an expansive selection of patient cases handled by the subject physician. During the meeting, the chair that claimed Dr. Heiden was a poor performer and was accurate in his assessments 93.8% of the time, which was below the hospital’s 97% threshold, according to Dr. Heiden’s lawsuit. Dr. Heiden disagreed with the results, and the two engaged in several more meetings.

Meanwhile, Dr. Heiden’s accommodation request was forwarded to other administrators. In an email introduced into court evidence, the chair indicated he did not support the accommodation, writing that Dr. Heiden’s “skill set does not meet the criteria for the initial installations” of the workstations.

On March 26, 2020, the chair allegedly asked Dr. Heiden to either resign or he would be terminated and reported to the New York State Office of Professional Medical Conduct. Four days later, Dr. Heiden learned that his accommodation request had been denied. He resigned on April 2, 2020.

In his lawsuit, Dr. Heiden claimed that the hospital discriminated against him on the basis of his disability in violation of ADA by denying him equal terms and conditions of employment and failing to provide a reasonable accommodation.

The defendants, who included the radiology chair, did not dispute that Dr. Heiden was asked to resign or that administrators warned termination, but they argued the impetus was his FPPE results and a history of inaccurate interpretations. Other clinicians and physicians had expressed concerns about Dr. Heiden’s “lack of clarity [and] interpretive errors,” according to deposition testimony. The hospital emphasized the FPPE had concluded before Dr. Heiden’s accommodation request was made.

New York City Health and Hospitals requested a federal judge dismiss the lawsuit for lack of valid claims. In January 2023, U.S. District Judge Lewis Liman allowed the case to proceed, ruling that some of Dr. Heiden’s claims had merit.

“Plaintiff has satisfied his obligation to proffer sufficient evidence to create an inference of retaliatory or discriminatory intent,” Judge Liman wrote in his decision. “[The chair] had not always planned to ask for plaintiff’s resignation based on the results of the FPPE completed on March 10, 2020. The decision to ask for that resignation arose shortly after the request for the accommodation. And there is evidence from which the jury could find that [the chair] was not receptive to making the accommodation.”

A jury trial was scheduled for July 2023, but the parties reached a settlement on May 31, 2023.
 

Is working from home reasonable for physicians?

The widespread swing to remote work in recent years has paved a smoother road for physicians who request the accommodation, said Peter Poullos, MD, clinical associate professor of radiology, gastroenterology, and hepatology at Stanford (Calif.) University and founder and cochair of the Stanford Medicine Alliance for Disability Inclusion and Equity.

“There is now a precedent and examples all over that working from home for some is a viable alternative to working in the hospital or a clinic,” Dr. Poullos said. “If a lawyer can point to instances of other people having received the same accommodation, even if the accommodation was given to someone without a disability, it’s much harder for an employer to say: ‘It’s not possible.’ Because clearly, it is.”

A key factor is the employee’s job duties and whether the employee can complete them remotely, said Mr. Dorfman. With physicians, the reasonableness would heavily depend on their specialty.

A radiologist, for example, would probably have a stronger case for performing their duties remotely compared with a surgeon, Dr. Poullos said.

In general, whether an accommodation is reasonable is decided on a case-by-case basis and usually includes reviewing supporting documentation from a medical provider, said Emily Harvey, a Denver-based disability law attorney. Employers are allowed to deny accommodations if they would cause an undue burden to the employer or fundamentally alter the nature or operation of the job or business.

“When it comes to the ADA, and disability rights in general, the analysis is based on the need of the individual,” she said. “Two people with identical diagnoses could need vastly different accommodations to be successful in the same job.”

Mr. Dorfman added that employers are only required to provide an accommodation that is reasonable under the circumstances, whether or not that accommodation meets the preferred request of the employee. For instance, if an immunocompromised physician asked to work from home, but the employer could ensure that all those working around the physician will mask, that could be reasonable enough.

A recent case analysis by Bloomberg Law shows that more courts are siding with employees who request remote work, compared with in past years. Employees who made disability-related remote work requests prevailed in 40% of federal court rulings from 2021 to 2023 versusa success rate of 30% from 2017 to 2019, according to the July 2023 analysis.

The analysis shows that employers still win the majority of the time, but that the gap is closing, Mr. Dorfman said.

In a September 2020 decision, for example, a Massachusetts District Court ruled in favor of an employee with asthma who was precluding from working at home by a behavioral and mental health agency. U.S. Magistrate Judge Katherine Robertson said that the manager was entitled to telework as a reasonable accommodation under the ADA for 60 days or until further notice. The lawsuit was settled in 2021.

“I think judges are much more used to working from home themselves,” Mr. Dorfman said. “That may affect their sense of accepting remote work as a reasonable accommodation. Their personal experience with it [may] actually inform their view of the topic.”
 

Your accommodation request was denied: Now what?

If you are unsure about your rights under the ADA, a first step is understanding the law’s protections and learning the obligations of your employer. 

Keep in mind that not everyone at your workplace may understand the law and what is required, said Dr. Poullos. When making a request to work from home, ensure that you’re using the right words and asking the right people, he advised. Some physicians, for instance, may only discuss the request with their direct supervisor and give up when the request is denied. “The employee might say, ‘I’ve been dealing with some medical issues and I’m really tired and need to adjust my schedule.’ They don’t mention the word ‘disability,’ they don’t mention the ADA, they don’t mention the word ‘accommodation,’ and so that might not trigger the appropriate response.”

Lisa Meeks, PhD, an expert and researcher in disabilities in medical education, encourages physicians and others to follow the appeals process at their institution if they feel their accommodation request has been unjustly denied.

Research shows that physicians who make accommodation requests rarely escalate denials to an appeal, grievance, or complaint, said Dr. Meeks, cohost of the Docs With Disabilities podcast and director of the Docs With Disabilities Initiative. The initiative aims to use research, education, and stories to drive change in perceptions, disability policy, and procedures in health professions and in biomedical and science education.

If an accommodation cannot be agreed on, doctors can reach out the Equal Employment Opportunity Commission and file a discrimination charge. The agency will review the case and provide an opinion on whether the charge has merit. The EEOC’s decision is not binding in court, and even if the agency believes the charge has no merit, employees still have the right to sue, he said.

Ms. Harvey added that the EEOC has many resources on its website, and that most states also have civil rights agencies that have additional resources. Every state and U.S. territory also has a protection and advocacy organization that may be able to help. Physicians can also review their state bar to locate and consult with disability rights attorneys.

Although it may seem like an uphill battle to push for an accommodation, it can be worth it in the end, said Michael Argenyi, MD, an addiction medicine specialist and assistant professor at the University of Massachusetts, Worcester. Dr. Argenyi, who has hearing loss, was featured on the Docs With Disabilities podcast.

“It’s difficult to ‘rock the boat’ and ask for support from the C-suite for employees with disabilities, or to rearrange a small medical office budget to establish a byline just for accommodations,” Dr. Argenyi said. “Yet, the payoff is worthwhile – patients and fellow colleagues notice commitments to diversity building and inclusion.”

A version of this article appeared on Medscape.com.