Opinion

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

The complex pathophysiology of obesity requires a multidisciplinary approach that includes lifestyle and medical interventions for successful management. Antiobesity medications (AOMs) have emerged as a powerful and life-changing tool for many individuals with obesity who are unable to sustain long-term weight loss through lifestyle changes alone. As with other chronic diseases such as hypertension and hyperlipidemia, the goal of decades of research has been to develop antiobesity medications with long-term efficacy and safety. Recent groundbreaking findings from a phase 2 trial show immense potential for a new AOM.

Here are five things to know about the role of agonists in the management of obesity.

1. Gut hormone physiology informs the development of AOMs.

The three hormones associated with obesity or diabetes are glucagonlike peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. GLP-1, a peptide released from the intestines in response to food ingestion, increases insulin production, reduces gut motility, and suppresses appetite. GIP is also an intestinal hormone that increases meal-stimulated insulin production and additionally facilitates lipolysis. Glucagon is known to increase hepatic glucose output but will also increase insulin secretion in the setting of hyperglycemia. Glucagon also promotes lipolysis.

Though these hormones are more commonly thought of as incretins, gut hormones that stimulate postprandial insulin secretion, their role in energy physiology is more diverse. Because of multiple mechanisms of action, incretins are increasingly referred to as nutrient-stimulated hormones (NuSH), a term which encompasses other peptides with therapeutic potential (e.g., amylin, oxyntomodulin, peptide tyrosine–tyrosine).

2. Studies have shown that NuSH therapies are highly effective AOMs.

In 2021 the Food and Drug Administration approved subcutaneous semaglutide 2.4 mg, a GLP-1 receptor agonist, for the treatment of obesity. Clinical trials demonstrating an average weight loss of 15% in patients taking semaglutide ushered in a new era of AOMs associated with significant weight loss that not only improve disease activity but also have the potential to achieve diabetes remission. Recent findings from the OASIS I trial demonstrated an average weight loss of 15.1% from baseline in patients treated with oral semaglutide for 68 weeks. Medical societies, including the American Diabetes Association and the American Association for the Study of Liver Diseases, recommend 10%-15% weight loss to fully treat weight-related comorbidities like type 2 diabetes and nonalcoholic fatty liver disease. In 2022, tirzepatide, a dual GLP-1 and GIP receptor agonist, demonstrated an average weight loss of 22.5% in phase 3 of the SURMOUNT-1 trial for obesity – a weight loss approaching that of some bariatric surgeries.

3. Clinical trial data show that the novel triple agonist retatrutide induces significant weight loss.

Preclinical studies on the newest NuSH therapy, triple GLP-1–GIP–glucagon receptor agonist retatrutide, showed predominant activity at the GIP receptor, with less GLP-1– and glucagon-receptor agonism than that of endogenous GLP-1 and GIP. Results from a phase 2 trial published in June 2023 showed a weight loss of 24% at 48 weeks in adults with obesity treated with retatrutide, which is the greatest weight loss reported in an obesity trial so far. Moreover, for the first time in obesity pharmacotherapy research, 100% of participants achieved clinically significant weight loss (defined as ≥ 5% of baseline weight).

4. Retatrutide may improve lipid metabolism.

In the phase 2 trial, retatrutide reduced low-density lipoprotein cholesterol levels by approximately 20%. This degree of reduced plasma LDL-C is dramatic in weight loss studies. Typically, weight loss significantly reduces triglyceride levels, increases high-density lipoprotein cholesterol levels, and has a modest effect on LDL-C reduction of about 5%.

A 20% reduction in LDL-C with retatrutide is hypothesis generating. Preclinical studies have shown glucagon to be an important regulator of proprotein convertase subtilisin/kexin type 9 degradation, with the lack of glucagon resulting in increased PCSK9 levels, decreased LDL receptors, and increased plasma LDL; conversely, treatment with glucagon decreased plasma LDL.

5. The long-term safety of retatrutide still needs to be determined.

In the 48-week phase 2 trial, retatrutide was observed to have a side-effect profile largely similar to other NuSH therapies (e.g., semaglutide 2.4 mg, tirzepatide), with a predominance of gastrointestinal symptoms including nausea, diarrhea, vomiting, and constipation. However, side effects potentially unique to retatrutide also emerged. Cutaneous hyperesthesia and skin sensitivity were reported in 7% of participants in the retatrutide group vs. 1% in the placebo group; none of these effects were associated with physical skin findings. Of note, 17 out of 198 (9%) participants in the retatrutide group developed cardiac arrhythmia vs. two out of 70 (3%) in the placebo group. There was no consistent pattern of arrhythmia type (e.g., supraventricular, ventricular) observed, and some of these events were reported as “palpitations” or “increased heart rate” without further detail. Phase 3 clinical trial data will provide further insight into the long-term safety of retatrutide.

Dr. Tchang is assistant professor of clinical medicine, division of endocrinology, Weill Cornell Medicine and physician, department of medicine, New York-Presbyterian/Weill Cornell Medical Center, both in New York. She has disclosed ties with Gelesis 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.

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.

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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

This transcript has been edited for clarity.

Hello. It’s Mark Kris from Memorial Sloan-Kettering, still musing on things I learned at ASCO 2023.

I learned that there is a new C word.

People used to be afraid to use the word “cancer,” so they would call it the C word. Hopefully we’ve gotten over that stigma, that cancer is an illness that can be fought like any other illness.

There’s a new C word now that people seem, again, afraid to use, and that word is “cure.” It’s almost a true rarity that – again, I’m talking about the lung cancer world in particular – folks use the word “cure.” I didn’t hear it at ASCO, but the truth of the matter is that’s a word we should be using and be using more.

What do our patients want? I think if you truly ask a patient what their goal of care should be, it would be to cure the illness. What I mean by “cure” is to eradicate the cancer that is in their body, keep the cancer and its effects from interfering with their ability to continue their lives, and to do it for the length of their natural life. That’s what our patients want. Yes, overall survival is important, but not as much as a life free of cancer and the burden that it puts on people having cancer in the body.

When you start thinking about cure and how to make it a goal of care, a number of issues immediately crop up. The first one is defining what is meant by “cure.” We don’t have a strict definition of cure. Again, I would probably go to the patients and ask them what they mean by it. There may be some landmark part of the definition that needs to be discussed and addressed, but again, to me it’s having your life not disturbed by cancer, and that generally comes by eradicating cancer. Living with cancer is harder than the living after cancer has been cured. But we don’t have a good definition.

We also don’t have a good way of designing clinical trials to assess whether the regimen is curative. I don’t think I’ve ever seen a trial in lung cancer that looked at the ability of any given treatment to cure patients. We need to come up with ways to design trials to do that. Now, in addition to clinical trials, we don’t have a good body of evidence to design our preclinical experiments to look for those treatments that can lead to cures, or total eradication of cancer in whatever model system might be used. If we make cure the goal, then we need to find ways preclinically to identify those strategies that could lead to that.

Also in the realm of clinical trials, we need a very clear statistical underpinning to show that one or another treatment has a better chance of cure and to show with scientific rigor that one treatment is better than the other when it comes to cure. I think there needs to be more attention to this, and as we think about revamping the clinical trial process, we need to focus more on cure.

I’m saving the most important step for last. None of this can happen unless we try to make it happen and we say cure is possible. My mentor, George Boswell, always taught us that we would, in every single patient with cancer, try to develop a curative strategy. Is there a curative strategy for this patient? If so, pursue it with all the tools and vigor that we have. We really need to think that way.

Obviously, not every patient with cancer can be cured with our current armamentarium of anticancer treatments, but we need to make sure we put it on the table. We need to [confirm] that a strategy does not currently exist that could lead to cure. And of course, if we do find that strategy, we need to pursue it with all the energy and resources that we have.

Please don’t be afraid to use the word “cure.” Our patients want that. They deserve it. We should work hard to try to provide it and work toward developing strategies that we can propose and cure more patients.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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

A patient inquires about whether he or she can use an EpiPen after the expiration date. What should you advise?

A. The EpiPen is unlikely to be effective after the expiration date.

B. The EpiPen may be dangerous to use after the expiration date.

C. The EpiPen is likely to be okay up to 2 years past the expiration date.

I think that choice C is the most accurate and will get to all the evidence shortly. The expiration date is not the date that the drug stops being effective or potentially becomes toxic. It is a date, required by law, that the manufacturer can guarantee greater than 90% original potency of the medication.

Epinephrine is a costly drug and is usually replaced when the Epipen expires. Weir and colleagues studied six epinephrine syringes 30 months past their expiration date.¹ Three of the syringes and one control, nonexpired syringe were analyzed using liquid chromatography-mass spectrometry and nuclear magnetic resonance to determine epinephrine content. The contents of the other three syringes of epinephrine were cultured for bacteria and fungus, which yielded no microbial growth. The study showed that the content of epinephrine present in the original sample remained unchanged, compared with the control.

Rachid et al. looked at 35 EpiPens 3-36 months past their expiration dates.² The percentage of epinephrine found remained 84%-101%, with all EpiPens less than 24 months past expiration having > 90% of the labeled epinephrine dose. Cantrell and colleagues evaluated a combination of 40 EpiPens and Epipen Jrs that were 1-50 months past expiration.³ These pens had not been kept in ideal conditions, as some had been in cars, outdoor cabins, and other environments without temperature control. Sixty-one percent of the Epipens and 56% of the EpiPen Juniors had > 90% of the labeled epinephrine content. I think expired Epipens can be used as a back-up option – that is, they are safe to use if there is not an Epipen available that is not expired.
 

Shelf life extension program

Lyon and colleagues reported data from the Shelf Life Extension Program (SLEP).⁴ A total of 122 drugs were studied representing 3,005 lots. Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. Several antibiotics were studied, including ciprofloxacin (mean extension, 55 months), amoxicillin (mean extension, 23 months), and doxycycline (mean extension, 50 months).

What about other drugs not in pill form?

I am frequently asked about the longevity of medication formulations that are not in pill form. For example, I have been asked about using expired eye drops. There are few data on this. Reis at al. studied whether travoprost that was past the expiration date still lowered intraocular pressures.⁵ Intraocular pressures in glaucoma patients treated with travoprost 6 weeks after the seal was broken were compared with pressures when drops were used immediately after the container seal was broken. There was no significant difference in intraocular pressure between the two treatment groups during the study.

I found one case report of harm from using expired eye medications. Use of expired eye drops was associated with a case of bilateral toxic epithelial keratopathy.⁶ Eye drops can be contaminated and cause irritation from the breakdown products of preservatives.

Many people use inhalers for many years. This is especially true for albuterol, which is often used for very intermittent symptoms. I found one recent study on the stability of albuterol. Kutty et al. studied expired albuterol inhalers and solutions up to 20 years past expiration.⁷ Almost all lots of albuterol maintained > 90% of product (73%-103%), many years past their expiration date. Even at 73% retained activity, the dose would likely be effective.
 

Pearl: Expired epinephrine and albuterol appear to retain activity several years past expiration.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He has no conflicts of interest. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Weir WB et al. Prehosp Emerg Care. 2018 Jul-Aug;22(4):414-8.

2. Rachid O et al. Ann Allergy Asthma Immunol. 2015 Apr;114(4):354-6.

3. Cantrell FL et al. Ann Intern Med. 2017 Jun 20;166(12):918-9.

4. Lyon RC et al. J Pharmaceut Sci. 2006;95(7):1549-60.

5. Reis R et al. Clin Ther. 2004 Dec;26(12):2121-7.

6. AlGhadeer H, AlHumaiden A. J Clin Pharm Ther. 2022 Dec;47(12):2379-82.

7. Kutty RG et al. Heliyon. 2022 Aug 5;8(8):e10104.

A patient inquires about whether he or she can use an EpiPen after the expiration date. What should you advise?

A. The EpiPen is unlikely to be effective after the expiration date.

B. The EpiPen may be dangerous to use after the expiration date.

C. The EpiPen is likely to be okay up to 2 years past the expiration date.

I think that choice C is the most accurate and will get to all the evidence shortly. The expiration date is not the date that the drug stops being effective or potentially becomes toxic. It is a date, required by law, that the manufacturer can guarantee greater than 90% original potency of the medication.

Epinephrine is a costly drug and is usually replaced when the Epipen expires. Weir and colleagues studied six epinephrine syringes 30 months past their expiration date.¹ Three of the syringes and one control, nonexpired syringe were analyzed using liquid chromatography-mass spectrometry and nuclear magnetic resonance to determine epinephrine content. The contents of the other three syringes of epinephrine were cultured for bacteria and fungus, which yielded no microbial growth. The study showed that the content of epinephrine present in the original sample remained unchanged, compared with the control.

Rachid et al. looked at 35 EpiPens 3-36 months past their expiration dates.² The percentage of epinephrine found remained 84%-101%, with all EpiPens less than 24 months past expiration having > 90% of the labeled epinephrine dose. Cantrell and colleagues evaluated a combination of 40 EpiPens and Epipen Jrs that were 1-50 months past expiration.³ These pens had not been kept in ideal conditions, as some had been in cars, outdoor cabins, and other environments without temperature control. Sixty-one percent of the Epipens and 56% of the EpiPen Juniors had > 90% of the labeled epinephrine content. I think expired Epipens can be used as a back-up option – that is, they are safe to use if there is not an Epipen available that is not expired.
 

Shelf life extension program

Lyon and colleagues reported data from the Shelf Life Extension Program (SLEP).⁴ A total of 122 drugs were studied representing 3,005 lots. Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. Several antibiotics were studied, including ciprofloxacin (mean extension, 55 months), amoxicillin (mean extension, 23 months), and doxycycline (mean extension, 50 months).

What about other drugs not in pill form?

I am frequently asked about the longevity of medication formulations that are not in pill form. For example, I have been asked about using expired eye drops. There are few data on this. Reis at al. studied whether travoprost that was past the expiration date still lowered intraocular pressures.⁵ Intraocular pressures in glaucoma patients treated with travoprost 6 weeks after the seal was broken were compared with pressures when drops were used immediately after the container seal was broken. There was no significant difference in intraocular pressure between the two treatment groups during the study.

I found one case report of harm from using expired eye medications. Use of expired eye drops was associated with a case of bilateral toxic epithelial keratopathy.⁶ Eye drops can be contaminated and cause irritation from the breakdown products of preservatives.

Many people use inhalers for many years. This is especially true for albuterol, which is often used for very intermittent symptoms. I found one recent study on the stability of albuterol. Kutty et al. studied expired albuterol inhalers and solutions up to 20 years past expiration.⁷ Almost all lots of albuterol maintained > 90% of product (73%-103%), many years past their expiration date. Even at 73% retained activity, the dose would likely be effective.
 

Pearl: Expired epinephrine and albuterol appear to retain activity several years past expiration.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He has no conflicts of interest. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Weir WB et al. Prehosp Emerg Care. 2018 Jul-Aug;22(4):414-8.

2. Rachid O et al. Ann Allergy Asthma Immunol. 2015 Apr;114(4):354-6.

3. Cantrell FL et al. Ann Intern Med. 2017 Jun 20;166(12):918-9.

4. Lyon RC et al. J Pharmaceut Sci. 2006;95(7):1549-60.

5. Reis R et al. Clin Ther. 2004 Dec;26(12):2121-7.

6. AlGhadeer H, AlHumaiden A. J Clin Pharm Ther. 2022 Dec;47(12):2379-82.

7. Kutty RG et al. Heliyon. 2022 Aug 5;8(8):e10104.

A patient inquires about whether he or she can use an EpiPen after the expiration date. What should you advise?

A. The EpiPen is unlikely to be effective after the expiration date.

B. The EpiPen may be dangerous to use after the expiration date.

C. The EpiPen is likely to be okay up to 2 years past the expiration date.

I think that choice C is the most accurate and will get to all the evidence shortly. The expiration date is not the date that the drug stops being effective or potentially becomes toxic. It is a date, required by law, that the manufacturer can guarantee greater than 90% original potency of the medication.

Epinephrine is a costly drug and is usually replaced when the Epipen expires. Weir and colleagues studied six epinephrine syringes 30 months past their expiration date.¹ Three of the syringes and one control, nonexpired syringe were analyzed using liquid chromatography-mass spectrometry and nuclear magnetic resonance to determine epinephrine content. The contents of the other three syringes of epinephrine were cultured for bacteria and fungus, which yielded no microbial growth. The study showed that the content of epinephrine present in the original sample remained unchanged, compared with the control.

Rachid et al. looked at 35 EpiPens 3-36 months past their expiration dates.² The percentage of epinephrine found remained 84%-101%, with all EpiPens less than 24 months past expiration having > 90% of the labeled epinephrine dose. Cantrell and colleagues evaluated a combination of 40 EpiPens and Epipen Jrs that were 1-50 months past expiration.³ These pens had not been kept in ideal conditions, as some had been in cars, outdoor cabins, and other environments without temperature control. Sixty-one percent of the Epipens and 56% of the EpiPen Juniors had > 90% of the labeled epinephrine content. I think expired Epipens can be used as a back-up option – that is, they are safe to use if there is not an Epipen available that is not expired.
 

Shelf life extension program

Lyon and colleagues reported data from the Shelf Life Extension Program (SLEP).⁴ A total of 122 drugs were studied representing 3,005 lots. Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. Several antibiotics were studied, including ciprofloxacin (mean extension, 55 months), amoxicillin (mean extension, 23 months), and doxycycline (mean extension, 50 months).

What about other drugs not in pill form?

I am frequently asked about the longevity of medication formulations that are not in pill form. For example, I have been asked about using expired eye drops. There are few data on this. Reis at al. studied whether travoprost that was past the expiration date still lowered intraocular pressures.⁵ Intraocular pressures in glaucoma patients treated with travoprost 6 weeks after the seal was broken were compared with pressures when drops were used immediately after the container seal was broken. There was no significant difference in intraocular pressure between the two treatment groups during the study.

I found one case report of harm from using expired eye medications. Use of expired eye drops was associated with a case of bilateral toxic epithelial keratopathy.⁶ Eye drops can be contaminated and cause irritation from the breakdown products of preservatives.

Many people use inhalers for many years. This is especially true for albuterol, which is often used for very intermittent symptoms. I found one recent study on the stability of albuterol. Kutty et al. studied expired albuterol inhalers and solutions up to 20 years past expiration.⁷ Almost all lots of albuterol maintained > 90% of product (73%-103%), many years past their expiration date. Even at 73% retained activity, the dose would likely be effective.
 

Pearl: Expired epinephrine and albuterol appear to retain activity several years past expiration.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He has no conflicts of interest. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Weir WB et al. Prehosp Emerg Care. 2018 Jul-Aug;22(4):414-8.

2. Rachid O et al. Ann Allergy Asthma Immunol. 2015 Apr;114(4):354-6.

3. Cantrell FL et al. Ann Intern Med. 2017 Jun 20;166(12):918-9.

4. Lyon RC et al. J Pharmaceut Sci. 2006;95(7):1549-60.

5. Reis R et al. Clin Ther. 2004 Dec;26(12):2121-7.

6. AlGhadeer H, AlHumaiden A. J Clin Pharm Ther. 2022 Dec;47(12):2379-82.

7. Kutty RG et al. Heliyon. 2022 Aug 5;8(8):e10104.

I wanted to very briefly highlight a truly extraordinary event in my professional experience as a clinical investigator for almost 40 years in the area of the gynecologic malignancies: the simultaneous publication in The New England Journal of Medicine of two landmark, paradigm-changing studies involving the management of advanced endometrial cancer.

City of Hope

In my career, of course, I’ve treated endometrial cancer, but the paradigm, the algorithms, and the strategies we’ve used have, for the most part, simply followed what we’ve done for ovarian cancer. If platinums worked in ovarian cancer, they probably worked in endometrial cancer, and that was true. If paclitaxel worked and had activity in ovarian cancer, it probably would in endometrial cancer, and that was true. It took some time, but basically, we use the same frontline chemotherapy in advanced or recurrent endometrial cancer as we’ve used in ovarian cancer, and on and on.

That world has changed, very much for the positive. Not only have pharmaceutical companies, academic investigators, and individual investigators in the community setting seen endometrial cancer as a major priority, but we have exciting new developments, and very specifically, of course, the immunotherapeutic agents known as checkpoint inhibitors.

One of these two papers was titled “Pembrolizumab Plus Chemotherapy in Advanced Endometrial Cancer” and the second one was titled “Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.” Obviously, these were separate studies, but both used checkpoint inhibitor plus the chemotherapeutic agents carboplatin-paclitaxel, compared with chemotherapy alone as frontline therapy for advanced or recurrent ovarian cancer and demonstrated a statistically significant, and in my opinion, highly clinically meaningful improvement, in progression-free survival in favor of the regimen that included the checkpoint inhibitors.

Clearly, we will need longer follow-up to see both the overall magnitude of the effect of these therapies on overall survival and the duration of the effect – the shape of the curve. Do we cure many more people? Do we delay time to progression and death? That remains to be seen.

But the outcomes we have now are remarkably positive for patients and have absolutely changed the standard of care in the management of recurrent or advanced endometrial cancer.

I should note that this includes both patients who have evidence of mismatch repair deficiency and those patients who do not have evidence of deficiency, which is a large patient population. These studies demonstrated the benefit to the entire population of patients.

However, on the basis of the data that we have – not only in endometrial cancer, but in other tumor types – the greatest impact was seen in patients with evidence of mismatch repair deficiency, where the immunotherapy agent has been shown to be most relevant; not exclusively, but most relevant.

These are very important papers. If you have an interest in endometrial cancer or immunotherapy, I would encourage you to read these papers. They change the paradigm of management for advanced endometrial cancer, and they clearly point out directions for future research in the management of this class of gynecologic cancers.

Dr. Markman is a professor in the department of medical oncology and therapeutics research at City of Hope in Duarte, Calif., and the president of Medicine & Science at City of Hope Atlanta, Chicago, and Phoenix. He reported conflicts of interest with AstraZeneca and GlaxoSmithKline.

This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

I wanted to very briefly highlight a truly extraordinary event in my professional experience as a clinical investigator for almost 40 years in the area of the gynecologic malignancies: the simultaneous publication in The New England Journal of Medicine of two landmark, paradigm-changing studies involving the management of advanced endometrial cancer.

City of Hope

In my career, of course, I’ve treated endometrial cancer, but the paradigm, the algorithms, and the strategies we’ve used have, for the most part, simply followed what we’ve done for ovarian cancer. If platinums worked in ovarian cancer, they probably worked in endometrial cancer, and that was true. If paclitaxel worked and had activity in ovarian cancer, it probably would in endometrial cancer, and that was true. It took some time, but basically, we use the same frontline chemotherapy in advanced or recurrent endometrial cancer as we’ve used in ovarian cancer, and on and on.

That world has changed, very much for the positive. Not only have pharmaceutical companies, academic investigators, and individual investigators in the community setting seen endometrial cancer as a major priority, but we have exciting new developments, and very specifically, of course, the immunotherapeutic agents known as checkpoint inhibitors.

One of these two papers was titled “Pembrolizumab Plus Chemotherapy in Advanced Endometrial Cancer” and the second one was titled “Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.” Obviously, these were separate studies, but both used checkpoint inhibitor plus the chemotherapeutic agents carboplatin-paclitaxel, compared with chemotherapy alone as frontline therapy for advanced or recurrent ovarian cancer and demonstrated a statistically significant, and in my opinion, highly clinically meaningful improvement, in progression-free survival in favor of the regimen that included the checkpoint inhibitors.

Clearly, we will need longer follow-up to see both the overall magnitude of the effect of these therapies on overall survival and the duration of the effect – the shape of the curve. Do we cure many more people? Do we delay time to progression and death? That remains to be seen.

But the outcomes we have now are remarkably positive for patients and have absolutely changed the standard of care in the management of recurrent or advanced endometrial cancer.

I should note that this includes both patients who have evidence of mismatch repair deficiency and those patients who do not have evidence of deficiency, which is a large patient population. These studies demonstrated the benefit to the entire population of patients.

However, on the basis of the data that we have – not only in endometrial cancer, but in other tumor types – the greatest impact was seen in patients with evidence of mismatch repair deficiency, where the immunotherapy agent has been shown to be most relevant; not exclusively, but most relevant.

These are very important papers. If you have an interest in endometrial cancer or immunotherapy, I would encourage you to read these papers. They change the paradigm of management for advanced endometrial cancer, and they clearly point out directions for future research in the management of this class of gynecologic cancers.

Dr. Markman is a professor in the department of medical oncology and therapeutics research at City of Hope in Duarte, Calif., and the president of Medicine & Science at City of Hope Atlanta, Chicago, and Phoenix. He reported conflicts of interest with AstraZeneca and GlaxoSmithKline.

This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

I wanted to very briefly highlight a truly extraordinary event in my professional experience as a clinical investigator for almost 40 years in the area of the gynecologic malignancies: the simultaneous publication in The New England Journal of Medicine of two landmark, paradigm-changing studies involving the management of advanced endometrial cancer.

City of Hope

In my career, of course, I’ve treated endometrial cancer, but the paradigm, the algorithms, and the strategies we’ve used have, for the most part, simply followed what we’ve done for ovarian cancer. If platinums worked in ovarian cancer, they probably worked in endometrial cancer, and that was true. If paclitaxel worked and had activity in ovarian cancer, it probably would in endometrial cancer, and that was true. It took some time, but basically, we use the same frontline chemotherapy in advanced or recurrent endometrial cancer as we’ve used in ovarian cancer, and on and on.

That world has changed, very much for the positive. Not only have pharmaceutical companies, academic investigators, and individual investigators in the community setting seen endometrial cancer as a major priority, but we have exciting new developments, and very specifically, of course, the immunotherapeutic agents known as checkpoint inhibitors.

One of these two papers was titled “Pembrolizumab Plus Chemotherapy in Advanced Endometrial Cancer” and the second one was titled “Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer.” Obviously, these were separate studies, but both used checkpoint inhibitor plus the chemotherapeutic agents carboplatin-paclitaxel, compared with chemotherapy alone as frontline therapy for advanced or recurrent ovarian cancer and demonstrated a statistically significant, and in my opinion, highly clinically meaningful improvement, in progression-free survival in favor of the regimen that included the checkpoint inhibitors.

Clearly, we will need longer follow-up to see both the overall magnitude of the effect of these therapies on overall survival and the duration of the effect – the shape of the curve. Do we cure many more people? Do we delay time to progression and death? That remains to be seen.

But the outcomes we have now are remarkably positive for patients and have absolutely changed the standard of care in the management of recurrent or advanced endometrial cancer.

I should note that this includes both patients who have evidence of mismatch repair deficiency and those patients who do not have evidence of deficiency, which is a large patient population. These studies demonstrated the benefit to the entire population of patients.

However, on the basis of the data that we have – not only in endometrial cancer, but in other tumor types – the greatest impact was seen in patients with evidence of mismatch repair deficiency, where the immunotherapy agent has been shown to be most relevant; not exclusively, but most relevant.

These are very important papers. If you have an interest in endometrial cancer or immunotherapy, I would encourage you to read these papers. They change the paradigm of management for advanced endometrial cancer, and they clearly point out directions for future research in the management of this class of gynecologic cancers.

Dr. Markman is a professor in the department of medical oncology and therapeutics research at City of Hope in Duarte, Calif., and the president of Medicine & Science at City of Hope Atlanta, Chicago, and Phoenix. He reported conflicts of interest with AstraZeneca and GlaxoSmithKline.

This transcript has been edited for clarity. 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.

Recorded Aug. 26, 2023. This transcript has been edited for clarity.

Robert A. Harrington, MD: I’m here with my good friend, Manesh Patel, from Duke University. We’re at the European Society of Cardiology (ESC) congress in Amsterdam, and I pulled Manesh into the studio for a conversation about something that’s really topical right now: sudden cardiac death in athletes.

What I hope to do [in this interview] is really pick Manesh’s brain on how we are thinking about this. Are we going to think about treatment issues? Are we going to think about prevention issues? Are we thinking about screening? We’ll try to make it practical.

Dr. Manesh Patel is chief of cardiovascular medicine at Duke University and also the director of the Duke Heart Center. Manesh, thanks for joining me here.
 

Bronny James and Damar Hamlin

Manesh R. Patel, MD: Excited to be here, Bob. Always.

Harrington: [Recently,] a news article comes out about the cause of Bronny James’ sudden cardiac death. Let me put this into a bigger societal context.

Last winter, Damar Hamlin, from the Buffalo Bills, suffered a traumatic injury on the field, and with that, had cardiac arrest. He’s back playing football – great to see. You and I are involved with the American Heart Association. He’s been very supportive of our efforts around things like CPR. He’s been terrific. It’s great to see him playing.

We know a little less about Bronny James. The news articles say the cause is both functional and anatomical, and it seems to be congenital, but we don’t have any details beyond this. Let’s not focus on the people; let’s focus on the topic.

Patel: I’m excited that we’re having the conversation. First and foremost, we’re excited that, with what we’ve seen on a national stage, these two individuals are doing well. They survived sudden cardiac death, which is a testament to all the things that we’ll talk about.

There are many important questions, like, is this increasing? Is this something we can prevent? And what are those things that might be happening to athletes?

Harrington: Can we predict it?

Patel: Right. I think the idea of sudden cardiac death in athletes is really a critical one for us to think about because it does concern participation and what we think about that. There are many experts who’ve been studying this for years that I now get to work with.

Harrington: Tell us a little bit about the kind of things you’ve been doing in this area.

Patel: Even before these events in the COVID era, we were wondering about athletes getting myocarditis, just in general, what do we know about that? People like Aaron Baggish, Kim Harmon, Jonathan Drezner, and others have been studying this.

Harrington: You and I did a show on athletes and COVID-19.

Patel: With the American Heart Association (AHA), the Cornell Foundation, and others, we started the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). This registry is across the United States, and athletes can sign up.

Harrington: Is it voluntary? Do the schools sign them up?

Patel: The athletes sign up. Team trainers and doctors talk to the athletes. We don’t really know the risks of some of these conditions. There’s a lot of gray area – people with certain conditions that were really interesting; aortas that are dilated in tall people.

Harrington: Long QT.

Patel: Long QT. There are certainly things that we know we should be intervening on and others where participation is a question. All of these we are trying to longitudinally put into the registry and follow them over time.

The second thing is understanding from the last Bethesda Conference that we want shared decision-making. There are going to be conditions where you say, “Look, I think your risk is high. You’ve a family history of sudden cardiac death. You have arrhythmias while you’re exercising.”

Harrington: You have a big, thick heart.

Patel: If you have hypertrophic cardiomyopathy, whether you’re an athlete or a 40-year-old adult, we’re going to have the same conversation. I think that holds. There’s a variety or a spectrum where we don’t know. I think the registry is one big step.

Thinking back to when somebody has an event, I would say take the teachable moment with the AHA and others to make sure your communities and your areas have automated external defibrillators (AEDs) and CPR training, and that we get to 100%: 100% response, 100% CPR, 100% defibrillation. I think that’s the first step.
 

Chain of survival

Harrington: Let’s really focus on the chain of survival. It is a chain: If any link is broken, your chance of survival really drops. We’ve had some well-known cases within our AHA community, including somebody who talks about it regularly: Kevin Volpp, from the University of Pennsylvania, a health economist. He had almost the perfect chain of survival. He had sudden cardiac death in a restaurant that was immediately observed, CPR started, EMTs called, and AED on the scene. Impressive.

Patel: That was in Cincinnati, where there are communities that have really worked on these things. I think you’re right. The chain of survival with rapid CPR to build a nation of survivors is key. The people at the AHA are helping us do this; there is a national call to make sure CPR is something that people feel comfortable doing. That they do it in men and women. They do it for anyone that goes down. And realize that it’s CPR that is hands-only. I think that’s an important lesson from Damar’s work, Nancy Brown’s, and AHA’s. Actually, schools in many countries require that to get through primary school.

Harrington: CPR training is a requirement to graduate from high school in some states.

Patel: My son just graduated from high school, and we spent time at his school making sure that everybody had access to CPR training. I think the way to do this is to start with that. Now, getting more specific about teams and athletes, I think most have emergency action plans, but it’s having action plans that work because of where you are and where the AED locations might be, or what the sport is. Having a plan on how you’re going to get that athlete to a place where you can help them recover is an important piece.

From there, I think the conversation for us is about what can we do as a society and as a country to answer some critical questions, including some real-world questions that people are asking: We had COVID-19 and we’re hearing these cases. Is this going up or down, and are these related?

Soon, hopefully the same group I talked about and others will have a publication, working with the NCAA to look at all of the deaths that they observed in NCAA Division I athletes over 20 years, including the sudden cardiac deaths. I won’t share the results because the publication isn’t out, but I think that’s the kind of important information that will help us understand if these rates are going up or down.

Harrington: What’s associated with that risk? Then we can start getting at whether it is something that, when we’re doing assessment for suitability for sports, has risk factors that should warrant more investigation.

Patel: Much like the field of cardiology, we haven’t enough of an evidence base, the right technologies, or the studies to determine how we should do screening, or not screening, across the board. Again, there is variation. There are some countries where anyone participating is going to get an ECG and an echocardiogram. There are other countries, like the United States, where it’s going to be a bit dependent on athlete risk.

Harrington: And where you live.

Patel: And where you live. Unfortunately, again, that brings in the idea that it might not be equitable in how we’re evaluating these individuals. I do think the opportunity to start to standardize that evaluation exists, and it likely comes from the ability to look back and say, “Here are some higher-risk individuals or some higher-risk scenarios.”

Harrington: Isn’t this what we do all the time in clinical medicine?

Patel: It’s going to be applied to a population that maybe is not as studied. I said this to you before we came on. The other thing is to make sure that the shared decision-making allows athletes who feel like they have a chance or want to play. During COVID, we had many college athletes, high school athletes, and kids not able to participate in sports. There was significant depression, feeling of loneliness, and even physical loss. People were actually getting less conditioned quickly. There’s a great benefit to sports participation.

Harrington: We were extrapolating from older data. If I’ve just had this new infection, COVID, and I’ve maybe got some signs of it in my heart, why can’t I exercise? That’s extrapolating from old myocarditis data.

Patel: We’re having to learn and follow it. I think there’s value in following that and getting those data. The second thing I think is really valuable is that we’ve shown that these individuals, if you do have these conversations and follow them, can participate and can be part of understanding the risk just like anything else.

Harrington: Is it sport specific? Are there some sports where maybe the conversation should be a little more intense than in other sports?

Patel: I think what we’ll see is that the conversations may be sport specific, and some may concern the number of athletes tested. At times, it’s pretty complicated. It does look like there are, as you know, different weight-bearing performance athletes, endurance athletes, or what I’ll call burst sports. There will probably be data that will identify certain sports where we may need to pay a bit more attention.

Harrington: What about the contact issues? Damar had a very specific thing, we think, happen to him. Football is a violent, contact-oriented sport, but fortunately we don’t regularly see what happened to Damar.

Patel: We’re talking about sudden cardiac death, but obviously, contact issues and neurologic evaluation is a whole other topic. That’s another big issue that I know many are following, and the NCAA is carefully, too. For Damar, I think we know that it was commotio cordis. At least when that happens, when there’s a ball or a trauma to the chest, those things have to be timed just so to actually lead to this event. Thankfully, it’s not very frequent, but it can happen.

Harrington: Hockey pucks, baseballs, soccer balls, a helmet to the chest ...

Patel: You have to be in a specific cycle of the squeeze. We don’t see that very frequently. I do think the evaluation and treatment, hopefully, makes a difference. One thing that we’re evolving in the screening world is our imaging; it’s getting better. We are not just doing echocardiograms; we are able to do other studies. There’s a mix of imaging and other technologies.

Is screening the answer?

Harrington: Let’s talk about that because screening is the area, I would say, with the most controversy – and a large amount of emotional controversy. Some argue that the data are not good enough to screen, or doctors are saying, “Wait a minute, why are we screening all these kids?” You said you were at your son’s high school doing CPR training. How many athletes are at his high school? There are many, and that’s a pretty small high school. Big communities, big universities, and the professional sports can afford it. Should we be doing this at the community level?

Patel: There have been some data. The Italians have done standard screening for some time, and it’s shown us that if you did echocardiograms in many individuals, you do find some cases that are hypertrophic cardiomyopathy in pathology. The issue is just how much you have to do and the resource utilization. I think as we get to a world where screening studies can happen with smaller technology and AI, that can be democratizing in how we get to athletes.

Harrington: Give an example of that. We were talking outside, you and I, about some of the new stethoscope technology.

Patel: Yes, stethoscopes are going to be one of the examples. We have stethoscopes that have the ability to get sounds and ECG signals, or at least some lead signals.

Harrington: Yes.

Patel: Potentially you can imagine that sound and ECG tracing in an AI environment, at least getting you from “everyone gets a listen with one stethoscope in their gym from their coach,” and it goes to the cloud. When there are enough questions, these are the ones that have to go further. Now, that’s a big study that has to be carried out; I’m not in any way saying we should do that.

Harrington: The technology is coming.

Patel: We start to see that our ability to rapidly do something to meet our athletes or our patients where they are will happen soon. Remember that the performance curve can vary, but once you have a sound where you can start to say that this is a regular flow murmur vs. “I’m worried about this,” especially as you mark it with ECG – that’s one example.

Smaller imaging is another example. For many years, ECGs have been talked about. There are entire courses that we run looking at ECGs in athletes. Remembering that Aaron Baggish and others are publishing that these individuals are large. When we look at their hearts, we see that they’re large, but when you adjust for size, often you can identify that many of them are within what we think are normal. Structurally, there are still many cases where you look at hearts and you’re asking, “Is this a thick heart? Is this noncompaction? Is this some pathology?”

That’s where you need imaging expertise. I think you have to have those individuals. I’m not advocating screening. I’m advocating studying it and that we should be thinking about the population. I don’t see a world where we don’t eventually start to really look to prevent those.

Harrington: Right. Whether it’s understanding that there are certain risk factors associated with this and we have to dedicate screening resources to those individuals, or if we want to do it more broadly on the population level to understand this with deeper dives into certain individuals, we’ve got to study it.

Patel: Some of the experts in sports medicine and sports cardiology have been collecting these data for a while. It’s time that we are there, because with these events we have the opportunity to share more of these data and maybe raise awareness – not in the teachable moment only – to get others to contribute.

I do believe that long term there’s an opportunity. We’ve seen that. We see that the rates, unfortunately, for marathon runners, where people unfortunately have events, seem to be higher. And we’ve seen the studies on troponin leaks in these individuals or evidence that there’s some effect on the heart from these events. We want people to be able to be long-term healthy.
 

Early defibrillation

Harrington: A large amount of work needs to be done. We talked with regard to screening, we’ve talked about CPR. We really need to have a nation of people who can do hands-only CPR. Let’s talk about AEDs, another key part of the chain of survival.

Patel: We have another important study going on, but an important message first: AEDs are critical to survival. We know that CPR is critical, but so is getting people to a defibrillator.

Harrington: Early defibrillation.

Patel: Early defibrillation. Early CPR is one of the biggest markers of making sure we perfuse people to get to early defibrillation, but then you have to get early defibrillation. There’s been a huge push in many communities, again, along with AHA and others, to make sure that AEDs are available not only in the U.S. but around the world. We’re at ESC and we see the push around the world to get AEDs available. They’ve come down in size and come down in cost, and that’s made it much more accessible. That’s really good. They’re still not always there.

We’ve seen really interesting randomized studies with people in some European countries where they have certain areas, just because of the locations, where bystanders will help get an AED  vs. randomizing to the EMS truck. They seem better in some of those variations. Chris Granger, at our institution, with Monique Starks, Dan Mark, and others, is doing a study in North Carolina where we’re testing different ways to potentially get AEDs in communities. We’re randomizing counties to one or two ways of getting AEDs to those individuals.

Harrington: Can you have an app where you just click “Find me an AED”?

Patel: Is there a world where the AED is found or is something bringing you the AED? Are there drones? Are there people driving? Are there ways that an AED is brought to the scene? All of those are going to be critical. It starts with continuing to figure out ways to support the costs of getting AEDs in places. The technology is continuing to evolve.

Harrington: It really is the premedical system stuff that makes the difference. Once EMS arrives with trained individuals who can defibrillate, they can transport you to a medical facility where trained physicians are at. It’s that pre-EMS thing that is so critical.

Patel: We talk often about athletes, but cardiac arrest care in general, and the chain of survival with CPR and AEDs, is critical. I still see patients in the CICU at Duke where, unfortunately, the biggest driver, as you just highlighted in that chain of survival, is how rapid we were in that golden hour. In the first 15 minutes, are you getting CPR, are you getting AED? Are you getting to a system?

Harrington: Are you getting a rapid transport?

Patel: Are you getting a neurologic assessment? Are you getting cooled or not? Those are important things.

Harrington: All right. Let’s try to wrap this up. Teachable moments, we talked about. One of the things about cases in prominent athletes is that it makes it to the newspaper and then it raises awareness. There is a drawing inference from a small group of cases to the broader societal issues. That’s an important topic.

We’ve talked about possible screening options, identifying at-risk individuals and high-risk individuals. A large amount of data has already been accumulated, but there is more work to be done. We focused on how to use those teachable moments to really influence the chain of survival, not just for athletes but for society at large.

I love your point about the Bethesda Conference on shared decision-making. Like with everything else, we have to have that two-way conversation: What are the athlete’s goals, hopes, and aspirations?

Patel: That group of experts, in addition to shared decision-making, gave us a whole list of conditions that we should be aware of and the cutpoints of where we think normal and not normal live for athletes. I think that’s used by many.

Can we build our systems to make research happen faster for the individuals? These athletes are at colleges that are obviously doing so much to make sure they’re okay. The people who are helping with this registry, and others, are going to continue to work to ask whether we can engage them as citizen participants and scientists. I think athletes are going to become some of our best advocates for why you’d want to know about yourself and how to perform CPR.

Harrington: I love the concept of citizen scientists, that we all have an obligation to contribute to the evidence base because we all want to use that evidence.

This has been a terrific conversation. I’ve been joined by my good friend, Dr. Manesh Patel from Duke University. I hope you’ve enjoyed our discussion here at the ESC. We have been taking a little break from the science going on around us to talk about sudden cardiac death in athletes. It really does have implications for broader societal concepts.

Dr. Harrington is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, New York, as well as a former president of the American Heart Association. He has disclosed the following relevant financial relationships: Research relationships with Baim Institute (DSMB); CSL (RCT executive committee); Janssen (RCT chair); National Heart, Lung, and Blood Institute (RCT executive committee, DSMB chair); Patient-Centered Outcomes Research Institute (RCT co-chair); Duke Clinical Research Institute. Consulting relationships with Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; Cytokinetics. Dr. Patel is professor of medicine, Duke University; chief, division of cardiology; director, Duke Heart Center, Duke University Medical Center, Durham, N.C. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bayer; Janssen; Novartis (consultant). Received research grant from Bayer; Janssen.

A version of this article appeared on Medscape.com.

Recorded Aug. 26, 2023. This transcript has been edited for clarity.

Robert A. Harrington, MD: I’m here with my good friend, Manesh Patel, from Duke University. We’re at the European Society of Cardiology (ESC) congress in Amsterdam, and I pulled Manesh into the studio for a conversation about something that’s really topical right now: sudden cardiac death in athletes.

What I hope to do [in this interview] is really pick Manesh’s brain on how we are thinking about this. Are we going to think about treatment issues? Are we going to think about prevention issues? Are we thinking about screening? We’ll try to make it practical.

Dr. Manesh Patel is chief of cardiovascular medicine at Duke University and also the director of the Duke Heart Center. Manesh, thanks for joining me here.
 

Bronny James and Damar Hamlin

Manesh R. Patel, MD: Excited to be here, Bob. Always.

Harrington: [Recently,] a news article comes out about the cause of Bronny James’ sudden cardiac death. Let me put this into a bigger societal context.

Last winter, Damar Hamlin, from the Buffalo Bills, suffered a traumatic injury on the field, and with that, had cardiac arrest. He’s back playing football – great to see. You and I are involved with the American Heart Association. He’s been very supportive of our efforts around things like CPR. He’s been terrific. It’s great to see him playing.

We know a little less about Bronny James. The news articles say the cause is both functional and anatomical, and it seems to be congenital, but we don’t have any details beyond this. Let’s not focus on the people; let’s focus on the topic.

Patel: I’m excited that we’re having the conversation. First and foremost, we’re excited that, with what we’ve seen on a national stage, these two individuals are doing well. They survived sudden cardiac death, which is a testament to all the things that we’ll talk about.

There are many important questions, like, is this increasing? Is this something we can prevent? And what are those things that might be happening to athletes?

Harrington: Can we predict it?

Patel: Right. I think the idea of sudden cardiac death in athletes is really a critical one for us to think about because it does concern participation and what we think about that. There are many experts who’ve been studying this for years that I now get to work with.

Harrington: Tell us a little bit about the kind of things you’ve been doing in this area.

Patel: Even before these events in the COVID era, we were wondering about athletes getting myocarditis, just in general, what do we know about that? People like Aaron Baggish, Kim Harmon, Jonathan Drezner, and others have been studying this.

Harrington: You and I did a show on athletes and COVID-19.

Patel: With the American Heart Association (AHA), the Cornell Foundation, and others, we started the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). This registry is across the United States, and athletes can sign up.

Harrington: Is it voluntary? Do the schools sign them up?

Patel: The athletes sign up. Team trainers and doctors talk to the athletes. We don’t really know the risks of some of these conditions. There’s a lot of gray area – people with certain conditions that were really interesting; aortas that are dilated in tall people.

Harrington: Long QT.

Patel: Long QT. There are certainly things that we know we should be intervening on and others where participation is a question. All of these we are trying to longitudinally put into the registry and follow them over time.

The second thing is understanding from the last Bethesda Conference that we want shared decision-making. There are going to be conditions where you say, “Look, I think your risk is high. You’ve a family history of sudden cardiac death. You have arrhythmias while you’re exercising.”

Harrington: You have a big, thick heart.

Patel: If you have hypertrophic cardiomyopathy, whether you’re an athlete or a 40-year-old adult, we’re going to have the same conversation. I think that holds. There’s a variety or a spectrum where we don’t know. I think the registry is one big step.

Thinking back to when somebody has an event, I would say take the teachable moment with the AHA and others to make sure your communities and your areas have automated external defibrillators (AEDs) and CPR training, and that we get to 100%: 100% response, 100% CPR, 100% defibrillation. I think that’s the first step.
 

Chain of survival

Harrington: Let’s really focus on the chain of survival. It is a chain: If any link is broken, your chance of survival really drops. We’ve had some well-known cases within our AHA community, including somebody who talks about it regularly: Kevin Volpp, from the University of Pennsylvania, a health economist. He had almost the perfect chain of survival. He had sudden cardiac death in a restaurant that was immediately observed, CPR started, EMTs called, and AED on the scene. Impressive.

Patel: That was in Cincinnati, where there are communities that have really worked on these things. I think you’re right. The chain of survival with rapid CPR to build a nation of survivors is key. The people at the AHA are helping us do this; there is a national call to make sure CPR is something that people feel comfortable doing. That they do it in men and women. They do it for anyone that goes down. And realize that it’s CPR that is hands-only. I think that’s an important lesson from Damar’s work, Nancy Brown’s, and AHA’s. Actually, schools in many countries require that to get through primary school.

Harrington: CPR training is a requirement to graduate from high school in some states.

Patel: My son just graduated from high school, and we spent time at his school making sure that everybody had access to CPR training. I think the way to do this is to start with that. Now, getting more specific about teams and athletes, I think most have emergency action plans, but it’s having action plans that work because of where you are and where the AED locations might be, or what the sport is. Having a plan on how you’re going to get that athlete to a place where you can help them recover is an important piece.

From there, I think the conversation for us is about what can we do as a society and as a country to answer some critical questions, including some real-world questions that people are asking: We had COVID-19 and we’re hearing these cases. Is this going up or down, and are these related?

Soon, hopefully the same group I talked about and others will have a publication, working with the NCAA to look at all of the deaths that they observed in NCAA Division I athletes over 20 years, including the sudden cardiac deaths. I won’t share the results because the publication isn’t out, but I think that’s the kind of important information that will help us understand if these rates are going up or down.

Harrington: What’s associated with that risk? Then we can start getting at whether it is something that, when we’re doing assessment for suitability for sports, has risk factors that should warrant more investigation.

Patel: Much like the field of cardiology, we haven’t enough of an evidence base, the right technologies, or the studies to determine how we should do screening, or not screening, across the board. Again, there is variation. There are some countries where anyone participating is going to get an ECG and an echocardiogram. There are other countries, like the United States, where it’s going to be a bit dependent on athlete risk.

Harrington: And where you live.

Patel: And where you live. Unfortunately, again, that brings in the idea that it might not be equitable in how we’re evaluating these individuals. I do think the opportunity to start to standardize that evaluation exists, and it likely comes from the ability to look back and say, “Here are some higher-risk individuals or some higher-risk scenarios.”

Harrington: Isn’t this what we do all the time in clinical medicine?

Patel: It’s going to be applied to a population that maybe is not as studied. I said this to you before we came on. The other thing is to make sure that the shared decision-making allows athletes who feel like they have a chance or want to play. During COVID, we had many college athletes, high school athletes, and kids not able to participate in sports. There was significant depression, feeling of loneliness, and even physical loss. People were actually getting less conditioned quickly. There’s a great benefit to sports participation.

Harrington: We were extrapolating from older data. If I’ve just had this new infection, COVID, and I’ve maybe got some signs of it in my heart, why can’t I exercise? That’s extrapolating from old myocarditis data.

Patel: We’re having to learn and follow it. I think there’s value in following that and getting those data. The second thing I think is really valuable is that we’ve shown that these individuals, if you do have these conversations and follow them, can participate and can be part of understanding the risk just like anything else.

Harrington: Is it sport specific? Are there some sports where maybe the conversation should be a little more intense than in other sports?

Patel: I think what we’ll see is that the conversations may be sport specific, and some may concern the number of athletes tested. At times, it’s pretty complicated. It does look like there are, as you know, different weight-bearing performance athletes, endurance athletes, or what I’ll call burst sports. There will probably be data that will identify certain sports where we may need to pay a bit more attention.

Harrington: What about the contact issues? Damar had a very specific thing, we think, happen to him. Football is a violent, contact-oriented sport, but fortunately we don’t regularly see what happened to Damar.

Patel: We’re talking about sudden cardiac death, but obviously, contact issues and neurologic evaluation is a whole other topic. That’s another big issue that I know many are following, and the NCAA is carefully, too. For Damar, I think we know that it was commotio cordis. At least when that happens, when there’s a ball or a trauma to the chest, those things have to be timed just so to actually lead to this event. Thankfully, it’s not very frequent, but it can happen.

Harrington: Hockey pucks, baseballs, soccer balls, a helmet to the chest ...

Patel: You have to be in a specific cycle of the squeeze. We don’t see that very frequently. I do think the evaluation and treatment, hopefully, makes a difference. One thing that we’re evolving in the screening world is our imaging; it’s getting better. We are not just doing echocardiograms; we are able to do other studies. There’s a mix of imaging and other technologies.

Is screening the answer?

Harrington: Let’s talk about that because screening is the area, I would say, with the most controversy – and a large amount of emotional controversy. Some argue that the data are not good enough to screen, or doctors are saying, “Wait a minute, why are we screening all these kids?” You said you were at your son’s high school doing CPR training. How many athletes are at his high school? There are many, and that’s a pretty small high school. Big communities, big universities, and the professional sports can afford it. Should we be doing this at the community level?

Patel: There have been some data. The Italians have done standard screening for some time, and it’s shown us that if you did echocardiograms in many individuals, you do find some cases that are hypertrophic cardiomyopathy in pathology. The issue is just how much you have to do and the resource utilization. I think as we get to a world where screening studies can happen with smaller technology and AI, that can be democratizing in how we get to athletes.

Harrington: Give an example of that. We were talking outside, you and I, about some of the new stethoscope technology.

Patel: Yes, stethoscopes are going to be one of the examples. We have stethoscopes that have the ability to get sounds and ECG signals, or at least some lead signals.

Harrington: Yes.

Patel: Potentially you can imagine that sound and ECG tracing in an AI environment, at least getting you from “everyone gets a listen with one stethoscope in their gym from their coach,” and it goes to the cloud. When there are enough questions, these are the ones that have to go further. Now, that’s a big study that has to be carried out; I’m not in any way saying we should do that.

Harrington: The technology is coming.

Patel: We start to see that our ability to rapidly do something to meet our athletes or our patients where they are will happen soon. Remember that the performance curve can vary, but once you have a sound where you can start to say that this is a regular flow murmur vs. “I’m worried about this,” especially as you mark it with ECG – that’s one example.

Smaller imaging is another example. For many years, ECGs have been talked about. There are entire courses that we run looking at ECGs in athletes. Remembering that Aaron Baggish and others are publishing that these individuals are large. When we look at their hearts, we see that they’re large, but when you adjust for size, often you can identify that many of them are within what we think are normal. Structurally, there are still many cases where you look at hearts and you’re asking, “Is this a thick heart? Is this noncompaction? Is this some pathology?”

That’s where you need imaging expertise. I think you have to have those individuals. I’m not advocating screening. I’m advocating studying it and that we should be thinking about the population. I don’t see a world where we don’t eventually start to really look to prevent those.

Harrington: Right. Whether it’s understanding that there are certain risk factors associated with this and we have to dedicate screening resources to those individuals, or if we want to do it more broadly on the population level to understand this with deeper dives into certain individuals, we’ve got to study it.

Patel: Some of the experts in sports medicine and sports cardiology have been collecting these data for a while. It’s time that we are there, because with these events we have the opportunity to share more of these data and maybe raise awareness – not in the teachable moment only – to get others to contribute.

I do believe that long term there’s an opportunity. We’ve seen that. We see that the rates, unfortunately, for marathon runners, where people unfortunately have events, seem to be higher. And we’ve seen the studies on troponin leaks in these individuals or evidence that there’s some effect on the heart from these events. We want people to be able to be long-term healthy.
 

Early defibrillation

Harrington: A large amount of work needs to be done. We talked with regard to screening, we’ve talked about CPR. We really need to have a nation of people who can do hands-only CPR. Let’s talk about AEDs, another key part of the chain of survival.

Patel: We have another important study going on, but an important message first: AEDs are critical to survival. We know that CPR is critical, but so is getting people to a defibrillator.

Harrington: Early defibrillation.

Patel: Early defibrillation. Early CPR is one of the biggest markers of making sure we perfuse people to get to early defibrillation, but then you have to get early defibrillation. There’s been a huge push in many communities, again, along with AHA and others, to make sure that AEDs are available not only in the U.S. but around the world. We’re at ESC and we see the push around the world to get AEDs available. They’ve come down in size and come down in cost, and that’s made it much more accessible. That’s really good. They’re still not always there.

We’ve seen really interesting randomized studies with people in some European countries where they have certain areas, just because of the locations, where bystanders will help get an AED  vs. randomizing to the EMS truck. They seem better in some of those variations. Chris Granger, at our institution, with Monique Starks, Dan Mark, and others, is doing a study in North Carolina where we’re testing different ways to potentially get AEDs in communities. We’re randomizing counties to one or two ways of getting AEDs to those individuals.

Harrington: Can you have an app where you just click “Find me an AED”?

Patel: Is there a world where the AED is found or is something bringing you the AED? Are there drones? Are there people driving? Are there ways that an AED is brought to the scene? All of those are going to be critical. It starts with continuing to figure out ways to support the costs of getting AEDs in places. The technology is continuing to evolve.

Harrington: It really is the premedical system stuff that makes the difference. Once EMS arrives with trained individuals who can defibrillate, they can transport you to a medical facility where trained physicians are at. It’s that pre-EMS thing that is so critical.

Patel: We talk often about athletes, but cardiac arrest care in general, and the chain of survival with CPR and AEDs, is critical. I still see patients in the CICU at Duke where, unfortunately, the biggest driver, as you just highlighted in that chain of survival, is how rapid we were in that golden hour. In the first 15 minutes, are you getting CPR, are you getting AED? Are you getting to a system?

Harrington: Are you getting a rapid transport?

Patel: Are you getting a neurologic assessment? Are you getting cooled or not? Those are important things.

Harrington: All right. Let’s try to wrap this up. Teachable moments, we talked about. One of the things about cases in prominent athletes is that it makes it to the newspaper and then it raises awareness. There is a drawing inference from a small group of cases to the broader societal issues. That’s an important topic.

We’ve talked about possible screening options, identifying at-risk individuals and high-risk individuals. A large amount of data has already been accumulated, but there is more work to be done. We focused on how to use those teachable moments to really influence the chain of survival, not just for athletes but for society at large.

I love your point about the Bethesda Conference on shared decision-making. Like with everything else, we have to have that two-way conversation: What are the athlete’s goals, hopes, and aspirations?

Patel: That group of experts, in addition to shared decision-making, gave us a whole list of conditions that we should be aware of and the cutpoints of where we think normal and not normal live for athletes. I think that’s used by many.

Can we build our systems to make research happen faster for the individuals? These athletes are at colleges that are obviously doing so much to make sure they’re okay. The people who are helping with this registry, and others, are going to continue to work to ask whether we can engage them as citizen participants and scientists. I think athletes are going to become some of our best advocates for why you’d want to know about yourself and how to perform CPR.

Harrington: I love the concept of citizen scientists, that we all have an obligation to contribute to the evidence base because we all want to use that evidence.

This has been a terrific conversation. I’ve been joined by my good friend, Dr. Manesh Patel from Duke University. I hope you’ve enjoyed our discussion here at the ESC. We have been taking a little break from the science going on around us to talk about sudden cardiac death in athletes. It really does have implications for broader societal concepts.

Dr. Harrington is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, New York, as well as a former president of the American Heart Association. He has disclosed the following relevant financial relationships: Research relationships with Baim Institute (DSMB); CSL (RCT executive committee); Janssen (RCT chair); National Heart, Lung, and Blood Institute (RCT executive committee, DSMB chair); Patient-Centered Outcomes Research Institute (RCT co-chair); Duke Clinical Research Institute. Consulting relationships with Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; Cytokinetics. Dr. Patel is professor of medicine, Duke University; chief, division of cardiology; director, Duke Heart Center, Duke University Medical Center, Durham, N.C. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bayer; Janssen; Novartis (consultant). Received research grant from Bayer; Janssen.

A version of this article appeared on Medscape.com.

Recorded Aug. 26, 2023. This transcript has been edited for clarity.

Robert A. Harrington, MD: I’m here with my good friend, Manesh Patel, from Duke University. We’re at the European Society of Cardiology (ESC) congress in Amsterdam, and I pulled Manesh into the studio for a conversation about something that’s really topical right now: sudden cardiac death in athletes.

What I hope to do [in this interview] is really pick Manesh’s brain on how we are thinking about this. Are we going to think about treatment issues? Are we going to think about prevention issues? Are we thinking about screening? We’ll try to make it practical.

Dr. Manesh Patel is chief of cardiovascular medicine at Duke University and also the director of the Duke Heart Center. Manesh, thanks for joining me here.
 

Bronny James and Damar Hamlin

Manesh R. Patel, MD: Excited to be here, Bob. Always.

Harrington: [Recently,] a news article comes out about the cause of Bronny James’ sudden cardiac death. Let me put this into a bigger societal context.

Last winter, Damar Hamlin, from the Buffalo Bills, suffered a traumatic injury on the field, and with that, had cardiac arrest. He’s back playing football – great to see. You and I are involved with the American Heart Association. He’s been very supportive of our efforts around things like CPR. He’s been terrific. It’s great to see him playing.

We know a little less about Bronny James. The news articles say the cause is both functional and anatomical, and it seems to be congenital, but we don’t have any details beyond this. Let’s not focus on the people; let’s focus on the topic.

Patel: I’m excited that we’re having the conversation. First and foremost, we’re excited that, with what we’ve seen on a national stage, these two individuals are doing well. They survived sudden cardiac death, which is a testament to all the things that we’ll talk about.

There are many important questions, like, is this increasing? Is this something we can prevent? And what are those things that might be happening to athletes?

Harrington: Can we predict it?

Patel: Right. I think the idea of sudden cardiac death in athletes is really a critical one for us to think about because it does concern participation and what we think about that. There are many experts who’ve been studying this for years that I now get to work with.

Harrington: Tell us a little bit about the kind of things you’ve been doing in this area.

Patel: Even before these events in the COVID era, we were wondering about athletes getting myocarditis, just in general, what do we know about that? People like Aaron Baggish, Kim Harmon, Jonathan Drezner, and others have been studying this.

Harrington: You and I did a show on athletes and COVID-19.

Patel: With the American Heart Association (AHA), the Cornell Foundation, and others, we started the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). This registry is across the United States, and athletes can sign up.

Harrington: Is it voluntary? Do the schools sign them up?

Patel: The athletes sign up. Team trainers and doctors talk to the athletes. We don’t really know the risks of some of these conditions. There’s a lot of gray area – people with certain conditions that were really interesting; aortas that are dilated in tall people.

Harrington: Long QT.

Patel: Long QT. There are certainly things that we know we should be intervening on and others where participation is a question. All of these we are trying to longitudinally put into the registry and follow them over time.

The second thing is understanding from the last Bethesda Conference that we want shared decision-making. There are going to be conditions where you say, “Look, I think your risk is high. You’ve a family history of sudden cardiac death. You have arrhythmias while you’re exercising.”

Harrington: You have a big, thick heart.

Patel: If you have hypertrophic cardiomyopathy, whether you’re an athlete or a 40-year-old adult, we’re going to have the same conversation. I think that holds. There’s a variety or a spectrum where we don’t know. I think the registry is one big step.

Thinking back to when somebody has an event, I would say take the teachable moment with the AHA and others to make sure your communities and your areas have automated external defibrillators (AEDs) and CPR training, and that we get to 100%: 100% response, 100% CPR, 100% defibrillation. I think that’s the first step.
 

Chain of survival

Harrington: Let’s really focus on the chain of survival. It is a chain: If any link is broken, your chance of survival really drops. We’ve had some well-known cases within our AHA community, including somebody who talks about it regularly: Kevin Volpp, from the University of Pennsylvania, a health economist. He had almost the perfect chain of survival. He had sudden cardiac death in a restaurant that was immediately observed, CPR started, EMTs called, and AED on the scene. Impressive.

Patel: That was in Cincinnati, where there are communities that have really worked on these things. I think you’re right. The chain of survival with rapid CPR to build a nation of survivors is key. The people at the AHA are helping us do this; there is a national call to make sure CPR is something that people feel comfortable doing. That they do it in men and women. They do it for anyone that goes down. And realize that it’s CPR that is hands-only. I think that’s an important lesson from Damar’s work, Nancy Brown’s, and AHA’s. Actually, schools in many countries require that to get through primary school.

Harrington: CPR training is a requirement to graduate from high school in some states.

Patel: My son just graduated from high school, and we spent time at his school making sure that everybody had access to CPR training. I think the way to do this is to start with that. Now, getting more specific about teams and athletes, I think most have emergency action plans, but it’s having action plans that work because of where you are and where the AED locations might be, or what the sport is. Having a plan on how you’re going to get that athlete to a place where you can help them recover is an important piece.

From there, I think the conversation for us is about what can we do as a society and as a country to answer some critical questions, including some real-world questions that people are asking: We had COVID-19 and we’re hearing these cases. Is this going up or down, and are these related?

Soon, hopefully the same group I talked about and others will have a publication, working with the NCAA to look at all of the deaths that they observed in NCAA Division I athletes over 20 years, including the sudden cardiac deaths. I won’t share the results because the publication isn’t out, but I think that’s the kind of important information that will help us understand if these rates are going up or down.

Harrington: What’s associated with that risk? Then we can start getting at whether it is something that, when we’re doing assessment for suitability for sports, has risk factors that should warrant more investigation.

Patel: Much like the field of cardiology, we haven’t enough of an evidence base, the right technologies, or the studies to determine how we should do screening, or not screening, across the board. Again, there is variation. There are some countries where anyone participating is going to get an ECG and an echocardiogram. There are other countries, like the United States, where it’s going to be a bit dependent on athlete risk.

Harrington: And where you live.

Patel: And where you live. Unfortunately, again, that brings in the idea that it might not be equitable in how we’re evaluating these individuals. I do think the opportunity to start to standardize that evaluation exists, and it likely comes from the ability to look back and say, “Here are some higher-risk individuals or some higher-risk scenarios.”

Harrington: Isn’t this what we do all the time in clinical medicine?

Patel: It’s going to be applied to a population that maybe is not as studied. I said this to you before we came on. The other thing is to make sure that the shared decision-making allows athletes who feel like they have a chance or want to play. During COVID, we had many college athletes, high school athletes, and kids not able to participate in sports. There was significant depression, feeling of loneliness, and even physical loss. People were actually getting less conditioned quickly. There’s a great benefit to sports participation.

Harrington: We were extrapolating from older data. If I’ve just had this new infection, COVID, and I’ve maybe got some signs of it in my heart, why can’t I exercise? That’s extrapolating from old myocarditis data.

Patel: We’re having to learn and follow it. I think there’s value in following that and getting those data. The second thing I think is really valuable is that we’ve shown that these individuals, if you do have these conversations and follow them, can participate and can be part of understanding the risk just like anything else.

Harrington: Is it sport specific? Are there some sports where maybe the conversation should be a little more intense than in other sports?

Patel: I think what we’ll see is that the conversations may be sport specific, and some may concern the number of athletes tested. At times, it’s pretty complicated. It does look like there are, as you know, different weight-bearing performance athletes, endurance athletes, or what I’ll call burst sports. There will probably be data that will identify certain sports where we may need to pay a bit more attention.

Harrington: What about the contact issues? Damar had a very specific thing, we think, happen to him. Football is a violent, contact-oriented sport, but fortunately we don’t regularly see what happened to Damar.

Patel: We’re talking about sudden cardiac death, but obviously, contact issues and neurologic evaluation is a whole other topic. That’s another big issue that I know many are following, and the NCAA is carefully, too. For Damar, I think we know that it was commotio cordis. At least when that happens, when there’s a ball or a trauma to the chest, those things have to be timed just so to actually lead to this event. Thankfully, it’s not very frequent, but it can happen.

Harrington: Hockey pucks, baseballs, soccer balls, a helmet to the chest ...

Patel: You have to be in a specific cycle of the squeeze. We don’t see that very frequently. I do think the evaluation and treatment, hopefully, makes a difference. One thing that we’re evolving in the screening world is our imaging; it’s getting better. We are not just doing echocardiograms; we are able to do other studies. There’s a mix of imaging and other technologies.

Is screening the answer?

Harrington: Let’s talk about that because screening is the area, I would say, with the most controversy – and a large amount of emotional controversy. Some argue that the data are not good enough to screen, or doctors are saying, “Wait a minute, why are we screening all these kids?” You said you were at your son’s high school doing CPR training. How many athletes are at his high school? There are many, and that’s a pretty small high school. Big communities, big universities, and the professional sports can afford it. Should we be doing this at the community level?

Patel: There have been some data. The Italians have done standard screening for some time, and it’s shown us that if you did echocardiograms in many individuals, you do find some cases that are hypertrophic cardiomyopathy in pathology. The issue is just how much you have to do and the resource utilization. I think as we get to a world where screening studies can happen with smaller technology and AI, that can be democratizing in how we get to athletes.

Harrington: Give an example of that. We were talking outside, you and I, about some of the new stethoscope technology.

Patel: Yes, stethoscopes are going to be one of the examples. We have stethoscopes that have the ability to get sounds and ECG signals, or at least some lead signals.

Harrington: Yes.

Patel: Potentially you can imagine that sound and ECG tracing in an AI environment, at least getting you from “everyone gets a listen with one stethoscope in their gym from their coach,” and it goes to the cloud. When there are enough questions, these are the ones that have to go further. Now, that’s a big study that has to be carried out; I’m not in any way saying we should do that.

Harrington: The technology is coming.

Patel: We start to see that our ability to rapidly do something to meet our athletes or our patients where they are will happen soon. Remember that the performance curve can vary, but once you have a sound where you can start to say that this is a regular flow murmur vs. “I’m worried about this,” especially as you mark it with ECG – that’s one example.

Smaller imaging is another example. For many years, ECGs have been talked about. There are entire courses that we run looking at ECGs in athletes. Remembering that Aaron Baggish and others are publishing that these individuals are large. When we look at their hearts, we see that they’re large, but when you adjust for size, often you can identify that many of them are within what we think are normal. Structurally, there are still many cases where you look at hearts and you’re asking, “Is this a thick heart? Is this noncompaction? Is this some pathology?”

That’s where you need imaging expertise. I think you have to have those individuals. I’m not advocating screening. I’m advocating studying it and that we should be thinking about the population. I don’t see a world where we don’t eventually start to really look to prevent those.

Harrington: Right. Whether it’s understanding that there are certain risk factors associated with this and we have to dedicate screening resources to those individuals, or if we want to do it more broadly on the population level to understand this with deeper dives into certain individuals, we’ve got to study it.

Patel: Some of the experts in sports medicine and sports cardiology have been collecting these data for a while. It’s time that we are there, because with these events we have the opportunity to share more of these data and maybe raise awareness – not in the teachable moment only – to get others to contribute.

I do believe that long term there’s an opportunity. We’ve seen that. We see that the rates, unfortunately, for marathon runners, where people unfortunately have events, seem to be higher. And we’ve seen the studies on troponin leaks in these individuals or evidence that there’s some effect on the heart from these events. We want people to be able to be long-term healthy.
 

Early defibrillation

Harrington: A large amount of work needs to be done. We talked with regard to screening, we’ve talked about CPR. We really need to have a nation of people who can do hands-only CPR. Let’s talk about AEDs, another key part of the chain of survival.

Patel: We have another important study going on, but an important message first: AEDs are critical to survival. We know that CPR is critical, but so is getting people to a defibrillator.

Harrington: Early defibrillation.

Patel: Early defibrillation. Early CPR is one of the biggest markers of making sure we perfuse people to get to early defibrillation, but then you have to get early defibrillation. There’s been a huge push in many communities, again, along with AHA and others, to make sure that AEDs are available not only in the U.S. but around the world. We’re at ESC and we see the push around the world to get AEDs available. They’ve come down in size and come down in cost, and that’s made it much more accessible. That’s really good. They’re still not always there.

We’ve seen really interesting randomized studies with people in some European countries where they have certain areas, just because of the locations, where bystanders will help get an AED  vs. randomizing to the EMS truck. They seem better in some of those variations. Chris Granger, at our institution, with Monique Starks, Dan Mark, and others, is doing a study in North Carolina where we’re testing different ways to potentially get AEDs in communities. We’re randomizing counties to one or two ways of getting AEDs to those individuals.

Harrington: Can you have an app where you just click “Find me an AED”?

Patel: Is there a world where the AED is found or is something bringing you the AED? Are there drones? Are there people driving? Are there ways that an AED is brought to the scene? All of those are going to be critical. It starts with continuing to figure out ways to support the costs of getting AEDs in places. The technology is continuing to evolve.

Harrington: It really is the premedical system stuff that makes the difference. Once EMS arrives with trained individuals who can defibrillate, they can transport you to a medical facility where trained physicians are at. It’s that pre-EMS thing that is so critical.

Patel: We talk often about athletes, but cardiac arrest care in general, and the chain of survival with CPR and AEDs, is critical. I still see patients in the CICU at Duke where, unfortunately, the biggest driver, as you just highlighted in that chain of survival, is how rapid we were in that golden hour. In the first 15 minutes, are you getting CPR, are you getting AED? Are you getting to a system?

Harrington: Are you getting a rapid transport?

Patel: Are you getting a neurologic assessment? Are you getting cooled or not? Those are important things.

Harrington: All right. Let’s try to wrap this up. Teachable moments, we talked about. One of the things about cases in prominent athletes is that it makes it to the newspaper and then it raises awareness. There is a drawing inference from a small group of cases to the broader societal issues. That’s an important topic.

We’ve talked about possible screening options, identifying at-risk individuals and high-risk individuals. A large amount of data has already been accumulated, but there is more work to be done. We focused on how to use those teachable moments to really influence the chain of survival, not just for athletes but for society at large.

I love your point about the Bethesda Conference on shared decision-making. Like with everything else, we have to have that two-way conversation: What are the athlete’s goals, hopes, and aspirations?

Patel: That group of experts, in addition to shared decision-making, gave us a whole list of conditions that we should be aware of and the cutpoints of where we think normal and not normal live for athletes. I think that’s used by many.

Can we build our systems to make research happen faster for the individuals? These athletes are at colleges that are obviously doing so much to make sure they’re okay. The people who are helping with this registry, and others, are going to continue to work to ask whether we can engage them as citizen participants and scientists. I think athletes are going to become some of our best advocates for why you’d want to know about yourself and how to perform CPR.

Harrington: I love the concept of citizen scientists, that we all have an obligation to contribute to the evidence base because we all want to use that evidence.

This has been a terrific conversation. I’ve been joined by my good friend, Dr. Manesh Patel from Duke University. I hope you’ve enjoyed our discussion here at the ESC. We have been taking a little break from the science going on around us to talk about sudden cardiac death in athletes. It really does have implications for broader societal concepts.

Dr. Harrington is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, New York, as well as a former president of the American Heart Association. He has disclosed the following relevant financial relationships: Research relationships with Baim Institute (DSMB); CSL (RCT executive committee); Janssen (RCT chair); National Heart, Lung, and Blood Institute (RCT executive committee, DSMB chair); Patient-Centered Outcomes Research Institute (RCT co-chair); Duke Clinical Research Institute. Consulting relationships with Atropos Health; Bitterroot Bio; Bristol Myers Squibb; BridgeBio; Element Science; Edwards Lifesciences; Foresite Labs; Medscape/WebMD Board of Directors for: American Heart Association; College of the Holy Cross; Cytokinetics. Dr. Patel is professor of medicine, Duke University; chief, division of cardiology; director, Duke Heart Center, Duke University Medical Center, Durham, N.C. He has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bayer; Janssen; Novartis (consultant). Received research grant from Bayer; Janssen.

A version of this article appeared on Medscape.com.

If you are a pediatrician, babies are your bread and butter. In fact, they are the whole enchilada. Without them you are going to starve. Even if you are an adolescent medicine specialist, the pipeline feeding your business begins with babies. The number of babies entering the conveyor belt that eventually ends up in your office is something that should interest you. It probably doesn’t surprise you to learn that the fertility rate in this country has fallen. In fact, it has now dipped below the “replacement” threshold of 2.1%.

Another number that might interest you is ideal family size. In others words, the number of children American adults consider when they are envisioning the ideal family. You may be surprised to learn that despite the downward dip on the fertility rate during the 2007-2009 recession and the pandemic, a significant number of Americans still believe that the ideal family includes three children. Looking at the broader population, the ideal family is around 2.5 children, which is a number that is up a little from the 1990s but has scarcely changed over the last 5 decades. Obviously, there is a gap between what the population as a whole believes and the reality of how many children the fertile population is producing. And, there is research that suggests that this gap between personal intention and ideal family size is growing. In other words, people may be saying they believe bigger families are a good thing ... if everything is going well in their life.

What is behind this gap and why is it growing? As people are delaying building their families, realities and expectations collide. Some examples? The impact of their student loans is greater than they anticipated. Climate change and news stories focused on political uncertainty can be unsettling. A person may end up marrying someone who doesn’t concur with their view of an ideal family. Fertility problems crop up with advancing age. The first child may have presented more of a challenge both physically, emotionally, and economically than new parents had expected.

If we agree that the fertility rate is an important number for our survival as a profession, can we agree that because of this vested interest we should become involved in helping families widen this growing gap between their view of the ideal family size and the realities of actually producing that family?

Maybe we don’t need to get involved. When the national climate – meteorologically, politically, and economically – improves families will start making more babies. Right now maybe the better option is to adjust our business model to the fluctuations in demand.

On the other hand, we could ask the American Academy of Pediatrics to join with the American Academy of Obstetricians and Gynecologists and hire a big name advertising agency to launch an ad campaign encouraging young and not so young adults to have more children. However, this might appear rather transparent and self-serving.

The best option is probably to continue to do what we are already doing, but try to do it better. If the challenges of having a first child are a major deterrent to having a second child, we should redouble our efforts toward making, if only in retrospect, that first parenting experience rewarding and enjoyable. That could come in the form of speaking out for parental leave, breastfeeding-friendly workplaces, and more affordable daycare. But it could also come in those scores of encounters we have every day in the office where we give solid, realistic, and compassionate advice on breastfeeding, sleep hygiene, and behavior management. If we can make those tough first 6 months of parenting go more smoothly and make the twos seem less terrible, we may see the average family size in our practice grow before our eyes.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

If you are a pediatrician, babies are your bread and butter. In fact, they are the whole enchilada. Without them you are going to starve. Even if you are an adolescent medicine specialist, the pipeline feeding your business begins with babies. The number of babies entering the conveyor belt that eventually ends up in your office is something that should interest you. It probably doesn’t surprise you to learn that the fertility rate in this country has fallen. In fact, it has now dipped below the “replacement” threshold of 2.1%.

Another number that might interest you is ideal family size. In others words, the number of children American adults consider when they are envisioning the ideal family. You may be surprised to learn that despite the downward dip on the fertility rate during the 2007-2009 recession and the pandemic, a significant number of Americans still believe that the ideal family includes three children. Looking at the broader population, the ideal family is around 2.5 children, which is a number that is up a little from the 1990s but has scarcely changed over the last 5 decades. Obviously, there is a gap between what the population as a whole believes and the reality of how many children the fertile population is producing. And, there is research that suggests that this gap between personal intention and ideal family size is growing. In other words, people may be saying they believe bigger families are a good thing ... if everything is going well in their life.

What is behind this gap and why is it growing? As people are delaying building their families, realities and expectations collide. Some examples? The impact of their student loans is greater than they anticipated. Climate change and news stories focused on political uncertainty can be unsettling. A person may end up marrying someone who doesn’t concur with their view of an ideal family. Fertility problems crop up with advancing age. The first child may have presented more of a challenge both physically, emotionally, and economically than new parents had expected.

If we agree that the fertility rate is an important number for our survival as a profession, can we agree that because of this vested interest we should become involved in helping families widen this growing gap between their view of the ideal family size and the realities of actually producing that family?

Maybe we don’t need to get involved. When the national climate – meteorologically, politically, and economically – improves families will start making more babies. Right now maybe the better option is to adjust our business model to the fluctuations in demand.

On the other hand, we could ask the American Academy of Pediatrics to join with the American Academy of Obstetricians and Gynecologists and hire a big name advertising agency to launch an ad campaign encouraging young and not so young adults to have more children. However, this might appear rather transparent and self-serving.

The best option is probably to continue to do what we are already doing, but try to do it better. If the challenges of having a first child are a major deterrent to having a second child, we should redouble our efforts toward making, if only in retrospect, that first parenting experience rewarding and enjoyable. That could come in the form of speaking out for parental leave, breastfeeding-friendly workplaces, and more affordable daycare. But it could also come in those scores of encounters we have every day in the office where we give solid, realistic, and compassionate advice on breastfeeding, sleep hygiene, and behavior management. If we can make those tough first 6 months of parenting go more smoothly and make the twos seem less terrible, we may see the average family size in our practice grow before our eyes.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

If you are a pediatrician, babies are your bread and butter. In fact, they are the whole enchilada. Without them you are going to starve. Even if you are an adolescent medicine specialist, the pipeline feeding your business begins with babies. The number of babies entering the conveyor belt that eventually ends up in your office is something that should interest you. It probably doesn’t surprise you to learn that the fertility rate in this country has fallen. In fact, it has now dipped below the “replacement” threshold of 2.1%.

Another number that might interest you is ideal family size. In others words, the number of children American adults consider when they are envisioning the ideal family. You may be surprised to learn that despite the downward dip on the fertility rate during the 2007-2009 recession and the pandemic, a significant number of Americans still believe that the ideal family includes three children. Looking at the broader population, the ideal family is around 2.5 children, which is a number that is up a little from the 1990s but has scarcely changed over the last 5 decades. Obviously, there is a gap between what the population as a whole believes and the reality of how many children the fertile population is producing. And, there is research that suggests that this gap between personal intention and ideal family size is growing. In other words, people may be saying they believe bigger families are a good thing ... if everything is going well in their life.

What is behind this gap and why is it growing? As people are delaying building their families, realities and expectations collide. Some examples? The impact of their student loans is greater than they anticipated. Climate change and news stories focused on political uncertainty can be unsettling. A person may end up marrying someone who doesn’t concur with their view of an ideal family. Fertility problems crop up with advancing age. The first child may have presented more of a challenge both physically, emotionally, and economically than new parents had expected.

If we agree that the fertility rate is an important number for our survival as a profession, can we agree that because of this vested interest we should become involved in helping families widen this growing gap between their view of the ideal family size and the realities of actually producing that family?

Maybe we don’t need to get involved. When the national climate – meteorologically, politically, and economically – improves families will start making more babies. Right now maybe the better option is to adjust our business model to the fluctuations in demand.

On the other hand, we could ask the American Academy of Pediatrics to join with the American Academy of Obstetricians and Gynecologists and hire a big name advertising agency to launch an ad campaign encouraging young and not so young adults to have more children. However, this might appear rather transparent and self-serving.

The best option is probably to continue to do what we are already doing, but try to do it better. If the challenges of having a first child are a major deterrent to having a second child, we should redouble our efforts toward making, if only in retrospect, that first parenting experience rewarding and enjoyable. That could come in the form of speaking out for parental leave, breastfeeding-friendly workplaces, and more affordable daycare. But it could also come in those scores of encounters we have every day in the office where we give solid, realistic, and compassionate advice on breastfeeding, sleep hygiene, and behavior management. If we can make those tough first 6 months of parenting go more smoothly and make the twos seem less terrible, we may see the average family size in our practice grow before our eyes.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

I’m not the smartest dermatologist in our department. We’re fortunate to have a few super-smarties, you know, the ones who can still recite all the genes in Jean Bolognia’s dermatology textbook and have “Dermpath Bowl Champion” plaques covering their walls. Yet as our chief, I often get requests for a second or third opinion, hoping somehow I’ll discover a diagnosis that others missed. Sometimes they are real diagnostic dilemmas. Oftentimes they’re just itchy.

Kaiser Permanente

Recently an itchy 73-year-old woman came to see me. She had seen several competent dermatologists, had comprehensive workups, and had reasonable, even aggressive, attempts at treating. Not much interesting in her history. Nothing on exam. Cancer workup was negative as was pretty much any autoimmune or allergic cause. Biopsy? Maybe a touch of “dermal hypersensitivity.” She was still upset at being told previously she might have scabies. “Scabies!” she said indignantly. “How could I have scabies? No one has touched this body in nearly 4 years!” That’s interesting, I thought.

The electronic medical record holds a lot of useful information. We spend hours combing through histories, labs, pathology, scans, drugs to search for clues that might help with diagnoses. One tab we hardly visit is demographics. Why should that matter, of course? Age, phone number, and address are typically not contributory. But for this woman there was a bit of data that mattered; I checked right after her remark. Marital status: Widowed. She couldn’t have had scabies because no one touches her. Anymore. As our comprehensive workup did not find a cause nor did treatments mitigate her symptoms, I wondered if loneliness might be a contributing factor. I asked if anyone else was itching, any family, any friends? “No, I live alone. I don’t have anyone.”

Loneliness is a huge health risk. Lacking personal connection has psychological and physical consequences, increasing the risk for depression, cardiovascular disease, and dementia for example. According to the U.S. Surgeon General, it increases the risk for premature death comparable to smoking 15 cigarettes a day. Yet, we rarely (ever?) ask people if they’re lonely. In part because we don’t have good treatments. Remedies for loneliness are mostly societal – reaching out to the widowed, creating spaces that encourage connection, organizing events that bring people together. I cannot type any of these into the EMR orders. However, merely mentioning that a patient could be lonely can be therapeutic. They might not recognize its impact or that they have agency to make it better. They also might not see how their lives still have meaning, an important comorbidity of loneliness.

Not long after her appointment was a 63-year-old man who complained of a burning scrotum. He worked as a knife sharpener, setting up a folding table at local groceries and farmers markets. COVID killed most of his gigs. Like the woman who didn’t have scabies, comprehensive workups turned up nothing. And seemingly nothing, including antibiotics, gabapentin, indomethacin, lidocaine, helped. At his last visit, we talked about his condition. We had also talked about the proper way to sharpen a knife. I came in prepared to offer something dramatic this visit, methotrexate, dupilumab? But before I could speak, he opened a recycled plastic grocery bag and dumped out knives of various sizes. Also a small ax. He then proceeded to show me how each knife has to be sharpened in its own way. Before leaving he handed me a well-worn Arkansas sharpening stone. “For you,” he said. I gave him no additional recommendations or treatments. He hasn’t been back to dermatology since.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

I’m not the smartest dermatologist in our department. We’re fortunate to have a few super-smarties, you know, the ones who can still recite all the genes in Jean Bolognia’s dermatology textbook and have “Dermpath Bowl Champion” plaques covering their walls. Yet as our chief, I often get requests for a second or third opinion, hoping somehow I’ll discover a diagnosis that others missed. Sometimes they are real diagnostic dilemmas. Oftentimes they’re just itchy.

Kaiser Permanente

Recently an itchy 73-year-old woman came to see me. She had seen several competent dermatologists, had comprehensive workups, and had reasonable, even aggressive, attempts at treating. Not much interesting in her history. Nothing on exam. Cancer workup was negative as was pretty much any autoimmune or allergic cause. Biopsy? Maybe a touch of “dermal hypersensitivity.” She was still upset at being told previously she might have scabies. “Scabies!” she said indignantly. “How could I have scabies? No one has touched this body in nearly 4 years!” That’s interesting, I thought.

The electronic medical record holds a lot of useful information. We spend hours combing through histories, labs, pathology, scans, drugs to search for clues that might help with diagnoses. One tab we hardly visit is demographics. Why should that matter, of course? Age, phone number, and address are typically not contributory. But for this woman there was a bit of data that mattered; I checked right after her remark. Marital status: Widowed. She couldn’t have had scabies because no one touches her. Anymore. As our comprehensive workup did not find a cause nor did treatments mitigate her symptoms, I wondered if loneliness might be a contributing factor. I asked if anyone else was itching, any family, any friends? “No, I live alone. I don’t have anyone.”

Loneliness is a huge health risk. Lacking personal connection has psychological and physical consequences, increasing the risk for depression, cardiovascular disease, and dementia for example. According to the U.S. Surgeon General, it increases the risk for premature death comparable to smoking 15 cigarettes a day. Yet, we rarely (ever?) ask people if they’re lonely. In part because we don’t have good treatments. Remedies for loneliness are mostly societal – reaching out to the widowed, creating spaces that encourage connection, organizing events that bring people together. I cannot type any of these into the EMR orders. However, merely mentioning that a patient could be lonely can be therapeutic. They might not recognize its impact or that they have agency to make it better. They also might not see how their lives still have meaning, an important comorbidity of loneliness.

Not long after her appointment was a 63-year-old man who complained of a burning scrotum. He worked as a knife sharpener, setting up a folding table at local groceries and farmers markets. COVID killed most of his gigs. Like the woman who didn’t have scabies, comprehensive workups turned up nothing. And seemingly nothing, including antibiotics, gabapentin, indomethacin, lidocaine, helped. At his last visit, we talked about his condition. We had also talked about the proper way to sharpen a knife. I came in prepared to offer something dramatic this visit, methotrexate, dupilumab? But before I could speak, he opened a recycled plastic grocery bag and dumped out knives of various sizes. Also a small ax. He then proceeded to show me how each knife has to be sharpened in its own way. Before leaving he handed me a well-worn Arkansas sharpening stone. “For you,” he said. I gave him no additional recommendations or treatments. He hasn’t been back to dermatology since.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

I’m not the smartest dermatologist in our department. We’re fortunate to have a few super-smarties, you know, the ones who can still recite all the genes in Jean Bolognia’s dermatology textbook and have “Dermpath Bowl Champion” plaques covering their walls. Yet as our chief, I often get requests for a second or third opinion, hoping somehow I’ll discover a diagnosis that others missed. Sometimes they are real diagnostic dilemmas. Oftentimes they’re just itchy.

Kaiser Permanente

Recently an itchy 73-year-old woman came to see me. She had seen several competent dermatologists, had comprehensive workups, and had reasonable, even aggressive, attempts at treating. Not much interesting in her history. Nothing on exam. Cancer workup was negative as was pretty much any autoimmune or allergic cause. Biopsy? Maybe a touch of “dermal hypersensitivity.” She was still upset at being told previously she might have scabies. “Scabies!” she said indignantly. “How could I have scabies? No one has touched this body in nearly 4 years!” That’s interesting, I thought.

The electronic medical record holds a lot of useful information. We spend hours combing through histories, labs, pathology, scans, drugs to search for clues that might help with diagnoses. One tab we hardly visit is demographics. Why should that matter, of course? Age, phone number, and address are typically not contributory. But for this woman there was a bit of data that mattered; I checked right after her remark. Marital status: Widowed. She couldn’t have had scabies because no one touches her. Anymore. As our comprehensive workup did not find a cause nor did treatments mitigate her symptoms, I wondered if loneliness might be a contributing factor. I asked if anyone else was itching, any family, any friends? “No, I live alone. I don’t have anyone.”

Loneliness is a huge health risk. Lacking personal connection has psychological and physical consequences, increasing the risk for depression, cardiovascular disease, and dementia for example. According to the U.S. Surgeon General, it increases the risk for premature death comparable to smoking 15 cigarettes a day. Yet, we rarely (ever?) ask people if they’re lonely. In part because we don’t have good treatments. Remedies for loneliness are mostly societal – reaching out to the widowed, creating spaces that encourage connection, organizing events that bring people together. I cannot type any of these into the EMR orders. However, merely mentioning that a patient could be lonely can be therapeutic. They might not recognize its impact or that they have agency to make it better. They also might not see how their lives still have meaning, an important comorbidity of loneliness.

Not long after her appointment was a 63-year-old man who complained of a burning scrotum. He worked as a knife sharpener, setting up a folding table at local groceries and farmers markets. COVID killed most of his gigs. Like the woman who didn’t have scabies, comprehensive workups turned up nothing. And seemingly nothing, including antibiotics, gabapentin, indomethacin, lidocaine, helped. At his last visit, we talked about his condition. We had also talked about the proper way to sharpen a knife. I came in prepared to offer something dramatic this visit, methotrexate, dupilumab? But before I could speak, he opened a recycled plastic grocery bag and dumped out knives of various sizes. Also a small ax. He then proceeded to show me how each knife has to be sharpened in its own way. Before leaving he handed me a well-worn Arkansas sharpening stone. “For you,” he said. I gave him no additional recommendations or treatments. He hasn’t been back to dermatology since.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

I’m a creature of habit. I suspect most of us are.

One can of Diet Coke on the drive to my office. Turn on the WiFi and air conditioning. Fire up the computer and unload my briefcase. Then do online refills, check the Astronomy Picture of the Day, look over the day’s schedule, turn on the Keurig, and make one cup of coffee. And so on.

I’m sure most of us have similar routines. Our brains are probably wired that way for survival, though the reasons aren’t the same anymore. Once it was get up, look outside the cave for predators, make sure the tribe is all accounted for, go to the stream for water, look for berries.

The fact is that automatic habits are critical for everything we do. Driving a car is really a series of repetitive tasks. Being able to put most of the ride on our brain’s autopilot allows us to move our attention to scanning the surroundings for changes, and to think about other items such as wonder what to do for dinner and if I remembered to turn off theWiFi and Keurig.

The practice of medicine is similar. Some things are internalized. Watching patients walk back to my office, looking at their hands as they fill out forms, hearing them introduce themselves, and other things that we subconsciously process as part of the exam before we’ve even officially begun the appointment. I quietly file such things away to be used later in the visit.

It certainly wasn’t always that way. In training we learn to filter out signal from noise, because the information available is huge. We all read tests of some sort. When I began reading EEGs, the images and lines were overwhelming, but with time and experience I became skilled at whittling down the mass of information into the things that really needed to be noted so I could turn pages faster (yes, youngsters, EEGs used to be on paper). Now, scanning the screen becomes a background habit, with the brain focusing more on things that stand out (or going back to thinking about what to do for dinner).

Over the millennia we’ve changed daily routines from something critical for survival to what we need for individual success in a chosen field. The brain in this way is the ultimate Swiss Army Knife – many tools available, but how we adapt and use them for our individual needs is variable.

Which is pretty impressive, actually. In the era of AI and computers, we each come with a (roughly) 2.5-petabyte hard drive that’s not only capable of storing all that information, but figuring out how to use it when we need to. The process is so smooth that we’re rarely aware of it. But what a marvel it is.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m a creature of habit. I suspect most of us are.

One can of Diet Coke on the drive to my office. Turn on the WiFi and air conditioning. Fire up the computer and unload my briefcase. Then do online refills, check the Astronomy Picture of the Day, look over the day’s schedule, turn on the Keurig, and make one cup of coffee. And so on.

I’m sure most of us have similar routines. Our brains are probably wired that way for survival, though the reasons aren’t the same anymore. Once it was get up, look outside the cave for predators, make sure the tribe is all accounted for, go to the stream for water, look for berries.

The fact is that automatic habits are critical for everything we do. Driving a car is really a series of repetitive tasks. Being able to put most of the ride on our brain’s autopilot allows us to move our attention to scanning the surroundings for changes, and to think about other items such as wonder what to do for dinner and if I remembered to turn off theWiFi and Keurig.

The practice of medicine is similar. Some things are internalized. Watching patients walk back to my office, looking at their hands as they fill out forms, hearing them introduce themselves, and other things that we subconsciously process as part of the exam before we’ve even officially begun the appointment. I quietly file such things away to be used later in the visit.

It certainly wasn’t always that way. In training we learn to filter out signal from noise, because the information available is huge. We all read tests of some sort. When I began reading EEGs, the images and lines were overwhelming, but with time and experience I became skilled at whittling down the mass of information into the things that really needed to be noted so I could turn pages faster (yes, youngsters, EEGs used to be on paper). Now, scanning the screen becomes a background habit, with the brain focusing more on things that stand out (or going back to thinking about what to do for dinner).

Over the millennia we’ve changed daily routines from something critical for survival to what we need for individual success in a chosen field. The brain in this way is the ultimate Swiss Army Knife – many tools available, but how we adapt and use them for our individual needs is variable.

Which is pretty impressive, actually. In the era of AI and computers, we each come with a (roughly) 2.5-petabyte hard drive that’s not only capable of storing all that information, but figuring out how to use it when we need to. The process is so smooth that we’re rarely aware of it. But what a marvel it is.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m a creature of habit. I suspect most of us are.

One can of Diet Coke on the drive to my office. Turn on the WiFi and air conditioning. Fire up the computer and unload my briefcase. Then do online refills, check the Astronomy Picture of the Day, look over the day’s schedule, turn on the Keurig, and make one cup of coffee. And so on.

I’m sure most of us have similar routines. Our brains are probably wired that way for survival, though the reasons aren’t the same anymore. Once it was get up, look outside the cave for predators, make sure the tribe is all accounted for, go to the stream for water, look for berries.

The fact is that automatic habits are critical for everything we do. Driving a car is really a series of repetitive tasks. Being able to put most of the ride on our brain’s autopilot allows us to move our attention to scanning the surroundings for changes, and to think about other items such as wonder what to do for dinner and if I remembered to turn off theWiFi and Keurig.

The practice of medicine is similar. Some things are internalized. Watching patients walk back to my office, looking at their hands as they fill out forms, hearing them introduce themselves, and other things that we subconsciously process as part of the exam before we’ve even officially begun the appointment. I quietly file such things away to be used later in the visit.

It certainly wasn’t always that way. In training we learn to filter out signal from noise, because the information available is huge. We all read tests of some sort. When I began reading EEGs, the images and lines were overwhelming, but with time and experience I became skilled at whittling down the mass of information into the things that really needed to be noted so I could turn pages faster (yes, youngsters, EEGs used to be on paper). Now, scanning the screen becomes a background habit, with the brain focusing more on things that stand out (or going back to thinking about what to do for dinner).

Over the millennia we’ve changed daily routines from something critical for survival to what we need for individual success in a chosen field. The brain in this way is the ultimate Swiss Army Knife – many tools available, but how we adapt and use them for our individual needs is variable.

Which is pretty impressive, actually. In the era of AI and computers, we each come with a (roughly) 2.5-petabyte hard drive that’s not only capable of storing all that information, but figuring out how to use it when we need to. The process is so smooth that we’re rarely aware of it. But what a marvel it is.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.