New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

With worldwide supplies of tocilizumab dwindling as the COVID-19 pandemic rages on, a shortage of the agent will persist “for at least the next several weeks,” according to Genentech, the Roche unit that manufactures tocilizumab under the trade name Actemra IV.

The World Health Organization and Unitaid have called on Genentech to guarantee equitable distribution of the biologic agent globally and to ease up on technology transfer restrictions to make the treatment more accessible.

At this point, supplies of tocilizumab for subcutaneous use to treat rheumatoid arthritis and its other approved indications for inflammatory conditions aren’t as dire, but Genentech is watching them as well, the company says.

In June, the Food and Drug Administration issued an emergency use authorization for intravenous tocilizumab for hospitalized COVID-19 patients. Since then, it has been included in the WHO Therapeutics and COVID-19: living guideline. And on the same day Genentech and Roche reported the tocilizumab shortage, the European Medicines Agency posted a statement that it had started evaluating RoActemra, the European brand name for tocilizumab, for hospitalized COVID-19 patients.

The FDA authorization has caused an unprecedented run on supplies for the biologic agent, which is FDA approved to treat RA, giant cell arteritis, systemic sclerosis–associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome. 
 

Depleted stocks

In the United States, stocks of the 200- and 400-mg units were unavailable, according to an FDA update in mid-August on its website, and the 80-mg/4-mL unit is available by drop ship only. Supplies of 80-mg units were expected to be depleted by the end of the third week in August, Genentech said in a press release.

The company expects to resupply stocks by the end of August. “However,” the Genentech statement added, “if the pandemic continues to spread at its current pace, we anticipate additional periods of stockout in the weeks and months ahead.”

For patients with RA or other approved indications taking the subcutaneous formulation – pens and prefilled syringes – supplies continue to be available, but, the company added, “the supply situation continues to evolve.” The subcutaneous formulations aren’t authorized for use in COVID-19 patients. However, the American Society of Health-System Pharmacists’ website lists the 162-mg/0.9-mL prefilled syringe as one of the products affected by the shortage.

In a separate statement, Roche said that demand for tocilizumab increased 300% in developing countries over prepandemic orders, and that U.S. demand spiked more than 400% in the first 2 weeks of August.

Roche laid out four reasons for the shortage: global manufacturing capacity limits; raw material shortages; the overall complex process of manufacturing biologic agents; and “the dynamically evolving nature of the pandemic.”

The Roche statement noted the company ramped up manufacturing of tocilizumab more than 100% over prepandemic capacity.

With regard to issues WHO and Unitaid raised in their statement, Roche stated that about 60% of its COVID-19 supplies have gone to developing countries, and that Roche and partner Chugai – both of whom hold tocilizumab-related patents – won’t assert any patents over its use for COVID-19 in low- and middle-income countries (LMICs) during the pandemic.

“Roche is in the midst of discussions with WHO and we are committed to support access in LMICs as much as we can,” a Roche spokesperson said in an interview.

Blair Solow, MD, chair of the American College of Rheumatology’s government affairs committee, said the organization supports the equitable distribution of tocilizumab. “We will work to ensure that our patients continue to have access to the medications they need,” she said. “We will continue to engage with the FDA and others to address shortages and ensure patient access to critical therapies.”

The ACR said that any health care professionals having difficulty getting tocilizumab IV or any other COVID-19-related issues can contact the organization at COVID@rheumatology.org.

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

With worldwide supplies of tocilizumab dwindling as the COVID-19 pandemic rages on, a shortage of the agent will persist “for at least the next several weeks,” according to Genentech, the Roche unit that manufactures tocilizumab under the trade name Actemra IV.

The World Health Organization and Unitaid have called on Genentech to guarantee equitable distribution of the biologic agent globally and to ease up on technology transfer restrictions to make the treatment more accessible.

At this point, supplies of tocilizumab for subcutaneous use to treat rheumatoid arthritis and its other approved indications for inflammatory conditions aren’t as dire, but Genentech is watching them as well, the company says.

In June, the Food and Drug Administration issued an emergency use authorization for intravenous tocilizumab for hospitalized COVID-19 patients. Since then, it has been included in the WHO Therapeutics and COVID-19: living guideline. And on the same day Genentech and Roche reported the tocilizumab shortage, the European Medicines Agency posted a statement that it had started evaluating RoActemra, the European brand name for tocilizumab, for hospitalized COVID-19 patients.

The FDA authorization has caused an unprecedented run on supplies for the biologic agent, which is FDA approved to treat RA, giant cell arteritis, systemic sclerosis–associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome. 
 

Depleted stocks

In the United States, stocks of the 200- and 400-mg units were unavailable, according to an FDA update in mid-August on its website, and the 80-mg/4-mL unit is available by drop ship only. Supplies of 80-mg units were expected to be depleted by the end of the third week in August, Genentech said in a press release.

The company expects to resupply stocks by the end of August. “However,” the Genentech statement added, “if the pandemic continues to spread at its current pace, we anticipate additional periods of stockout in the weeks and months ahead.”

For patients with RA or other approved indications taking the subcutaneous formulation – pens and prefilled syringes – supplies continue to be available, but, the company added, “the supply situation continues to evolve.” The subcutaneous formulations aren’t authorized for use in COVID-19 patients. However, the American Society of Health-System Pharmacists’ website lists the 162-mg/0.9-mL prefilled syringe as one of the products affected by the shortage.

In a separate statement, Roche said that demand for tocilizumab increased 300% in developing countries over prepandemic orders, and that U.S. demand spiked more than 400% in the first 2 weeks of August.

Roche laid out four reasons for the shortage: global manufacturing capacity limits; raw material shortages; the overall complex process of manufacturing biologic agents; and “the dynamically evolving nature of the pandemic.”

The Roche statement noted the company ramped up manufacturing of tocilizumab more than 100% over prepandemic capacity.

With regard to issues WHO and Unitaid raised in their statement, Roche stated that about 60% of its COVID-19 supplies have gone to developing countries, and that Roche and partner Chugai – both of whom hold tocilizumab-related patents – won’t assert any patents over its use for COVID-19 in low- and middle-income countries (LMICs) during the pandemic.

“Roche is in the midst of discussions with WHO and we are committed to support access in LMICs as much as we can,” a Roche spokesperson said in an interview.

Blair Solow, MD, chair of the American College of Rheumatology’s government affairs committee, said the organization supports the equitable distribution of tocilizumab. “We will work to ensure that our patients continue to have access to the medications they need,” she said. “We will continue to engage with the FDA and others to address shortages and ensure patient access to critical therapies.”

The ACR said that any health care professionals having difficulty getting tocilizumab IV or any other COVID-19-related issues can contact the organization at COVID@rheumatology.org.

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

With worldwide supplies of tocilizumab dwindling as the COVID-19 pandemic rages on, a shortage of the agent will persist “for at least the next several weeks,” according to Genentech, the Roche unit that manufactures tocilizumab under the trade name Actemra IV.

The World Health Organization and Unitaid have called on Genentech to guarantee equitable distribution of the biologic agent globally and to ease up on technology transfer restrictions to make the treatment more accessible.

At this point, supplies of tocilizumab for subcutaneous use to treat rheumatoid arthritis and its other approved indications for inflammatory conditions aren’t as dire, but Genentech is watching them as well, the company says.

In June, the Food and Drug Administration issued an emergency use authorization for intravenous tocilizumab for hospitalized COVID-19 patients. Since then, it has been included in the WHO Therapeutics and COVID-19: living guideline. And on the same day Genentech and Roche reported the tocilizumab shortage, the European Medicines Agency posted a statement that it had started evaluating RoActemra, the European brand name for tocilizumab, for hospitalized COVID-19 patients.

The FDA authorization has caused an unprecedented run on supplies for the biologic agent, which is FDA approved to treat RA, giant cell arteritis, systemic sclerosis–associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome. 
 

Depleted stocks

In the United States, stocks of the 200- and 400-mg units were unavailable, according to an FDA update in mid-August on its website, and the 80-mg/4-mL unit is available by drop ship only. Supplies of 80-mg units were expected to be depleted by the end of the third week in August, Genentech said in a press release.

The company expects to resupply stocks by the end of August. “However,” the Genentech statement added, “if the pandemic continues to spread at its current pace, we anticipate additional periods of stockout in the weeks and months ahead.”

For patients with RA or other approved indications taking the subcutaneous formulation – pens and prefilled syringes – supplies continue to be available, but, the company added, “the supply situation continues to evolve.” The subcutaneous formulations aren’t authorized for use in COVID-19 patients. However, the American Society of Health-System Pharmacists’ website lists the 162-mg/0.9-mL prefilled syringe as one of the products affected by the shortage.

In a separate statement, Roche said that demand for tocilizumab increased 300% in developing countries over prepandemic orders, and that U.S. demand spiked more than 400% in the first 2 weeks of August.

Roche laid out four reasons for the shortage: global manufacturing capacity limits; raw material shortages; the overall complex process of manufacturing biologic agents; and “the dynamically evolving nature of the pandemic.”

The Roche statement noted the company ramped up manufacturing of tocilizumab more than 100% over prepandemic capacity.

With regard to issues WHO and Unitaid raised in their statement, Roche stated that about 60% of its COVID-19 supplies have gone to developing countries, and that Roche and partner Chugai – both of whom hold tocilizumab-related patents – won’t assert any patents over its use for COVID-19 in low- and middle-income countries (LMICs) during the pandemic.

“Roche is in the midst of discussions with WHO and we are committed to support access in LMICs as much as we can,” a Roche spokesperson said in an interview.

Blair Solow, MD, chair of the American College of Rheumatology’s government affairs committee, said the organization supports the equitable distribution of tocilizumab. “We will work to ensure that our patients continue to have access to the medications they need,” she said. “We will continue to engage with the FDA and others to address shortages and ensure patient access to critical therapies.”

The ACR said that any health care professionals having difficulty getting tocilizumab IV or any other COVID-19-related issues can contact the organization at COVID@rheumatology.org.

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

The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.

Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.

The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m², in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m².


EMPEROR-Reduced results drive approval

The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.

Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.


Empagliflozin joins dapagliflozin for treating HFrEF

Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.

Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.

mzoler@mdedge.com

The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.

Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.

The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m², in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m².


EMPEROR-Reduced results drive approval

The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.

Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.


Empagliflozin joins dapagliflozin for treating HFrEF

Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.

Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.

mzoler@mdedge.com

The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.

Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.

The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m², in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m².


EMPEROR-Reduced results drive approval

The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.

Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.


Empagliflozin joins dapagliflozin for treating HFrEF

Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.

Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.

mzoler@mdedge.com

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In this study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used "to reduce risk of ADAs and enhance efficacy of anti-TNF therapy."

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In this study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used "to reduce risk of ADAs and enhance efficacy of anti-TNF therapy."

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

The use fluoroquinolones or macrolides reduced immunogenicity risk in inflammatory bowel disease (IBD) patients on anti–tumor necrosis factor (anti-TNF) therapy, according to data from nearly 2,000 individuals.

luchschen/Thinkstock

Anti-TNF therapy with monoclonal antibodies is an established treatment for Crohn’s disease and ulcerative colitis, but approximately 40% of patients fail to respond initially and even more fail to achieve complete remission, wrote Yuri Gorelik, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues.

“Immunogenicity, which refers to the development of antidrug antibodies [ADA] is considered as the main factor driving secondary loss of response and is likely involved in primary nonresponse as well,” but data on how to predict the risk for ADA formation are limited, they said.

In a study published in Gut, the researchers identified data from 1,946 IBD patients using the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all IBD patients in Israel.

A total of 363 patients had positive ADA after a median follow-up period of 651 days after starting therapy. Overall, the risk of ADA development was significantly higher in patients on cephalosporins (adjusted hazard ratio, 1.97; 95% confidence interval, 1.58-2.44) or penicillin with beta-lactamase inhibitors (BLIs) (aHR, 1.38; 95% CI, 1.13-1.74) during anti-TNF therapy, and it was higher still for patients using both. By contrast, the risk was lower in patients on macrolides (aHR, 0.36; 95% CI, 0.16-0.82) or fluoroquinolones (aHR, 0.20; 95% CI; 95% CI, 0.12-0.35). All P values were less than .05 when compared with nontreated groups.

In the same study, the researchers reported data on mice treated with antibiotics and challenged with infliximab to evaluate the causative effect of antibiotics and the associated disruption to the gut microbiome on the formation of ADA. After 14 days, the researchers found significantly increased ADA production in mice treated with cephalosporins, compared with those treated with macrolides, but germ-free mice produced no ADA, which supports the role of microbial composition on ADA production.

The investigators cited previous research into the microbiome as a biomarker for prediction response to anti-TNF therapy; past results have also suggested that the effect of cephalosporins and penicillin-BLIs could be explained by the particular dysbiosis induced by those agents.

The study findings were limited by several factors including the retrospective design and potential for selection bias, as well as the inability to adjust antibiotic exposure according to type and severity of infection, they noted. However, “this is the first large scale study that extensively evaluated the effect of different antibiotic classes on immunogenicity of anti-TNF therapy,” and the results suggest that ADA development during anti-TNF therapy may to reduced by the use of fluoroquinolones and macrolides.

“Specific microbial manipulation may serve as a tool to modify immunogenicity which is preferably turned on for protective immunizations and off for biological therapy,” they noted. “Further studies involving detailed analysis of the antibiotic effects on the human microbiome and immune milieu are needed, as well as comparative experiments with other medications used to reduce immunogenicity.”
 

Unexpected findings may drive future drug choices

“Development of antidrug antibodies in patients on biologics for inflammatory bowel disease is an important mechanism for loss of response to a therapeutic agent,” Kim L. Isaacs, MD, AGAF, of the University of North Carolina at Chapel Hill, said in an interview. “To date the causes of development of ADAs is relatively understudied. Our approach to prevent ADA includes increasing immunosuppression in patients most commonly with combination therapy with thiopurines. If factors that provoke or prevent antibody formation are elucidated, therapy can be tailored to prevent ADAs and maximize the duration of response of many of our biologic therapies.”

A prior study performed by the ABIRISK European consortium demonstrated associations with antibiotics. “In this study, there was a differential effect of cephalosporins/penicillins (increased immunogenicity) and macrolides (decreased immunogenicity),” she said. “These studies suggest that the microbiome may be important in ADA formation to biologics – this is a concept that is novel and unexpected.

“The rationale for the choice of antibiotics in the population studied is not known, and it is possible that different infections may have led to different antibiotic choices, which in turn may have affected immunogenicity,” said Dr. Isaacs. However, clinicians might be able to tailor antibiotic choice in the future if the microbiome is playing a major role in risk for development of ADA.

“Further research is needed to further correlate microbiome changes with immunogenicity, to look at other classes of antibiotics and their role in immunogenicity, and to clarify the infections or reasons that these patients are receiving antibiotics,” Dr. Isaacs concluded.
 

Understanding the microbiome

Recent observations have shown associations between clinical response to anti-TNF and gut microbiota composition, noted Jatin Roper, MD, of Duke University, Durham, N.C. “More broadly, a growing body of evidence suggests that the gut microbiota modulates the metabolism of many therapeutic agents, as well as immune responses to infections.”

That said, Dr. Roper was surprised that “clinical use of different antibiotics, often short term, had such distinct effects on ADA levels.” Furthermore, “these findings suggest that distinct microbiota or microbial metabolic products impact antibody development to common immunomodulatory therapies in opposite ways,” which is itself a surprising finding.

Such antibodies to anti-TNF therapy are common in IBD, he said, but one implication of the study is how antibiotics could be carefully used "to reduce risk of ADAs and enhance efficacy of anti-TNF therapy."

However, because any antibiotic therapy will modify the gut microbiome and lead to unwanted effects, “further research is needed on how these agents impact the gut microbiome, with the ultimate goal of identifying specific microbiota or microbial metabolic products that can reproduce the intriguing findings of this paper.”

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust and the Israeli Ministry of Science and Technology. Dr. Gorelik had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple pharmaceutical companies including AbbVie, CytoReason, Takeda, and Pfizer. Dr. Isaacs had no financial conflicts to disclose, but serves on the GI&Hepatology News board of editors. Dr. Roper had no relevant disclosures.

Rates of minor diabetes-related lower extremity amputations (LEAs) in hospitalized patients increased between 2009 and 2017 in all racial and ethnic groups, in both rural and urban areas, and in all geographic regions across the United States, a new retrospective, observational study indicates.

In contrast, major lower extremity amputation rates held steady during the study period with a few exceptions.

There was also a decline in major-to-minor amputation ratios, especially among Native Americans – a sign that diabetes was being better managed and foot ulcers were being caught earlier, preventing the need for a major amputation above the foot or below or above the knee.

Minor LEAs include the loss of a toe, toes, or a foot.

“While I know an amputation is devastating either way, having a minor amputation is better than having a major amputation, and trends [at least to 2017] show that comprehensive foot examinations are paying off,” lead author Marvellous Akinlotan, PhD, MPH, a research associate at the Southwest Rural Health Research Center in Bryan, Texas, said in an interview.

Asked to comment, Marcia Ory, PhD, MPH, director of the Center for Population Health & Aging, Texas A&M School of Public Health, College Station, who was not involved in the study, said: “It points to some successes, but it also points to the need for continued education and preventive care to reduce all types of amputations.”

The study was published online in Diabetes Care.
 

Amputations increased during COVID-19

However, the study was conducted prior to the COVID-19 pandemic, and amputation rates appear to have significantly worsened during the past 18 months.

In a summary of recent evidence collated by the Amputee Coalition, the authors point out that not only does COVID-19 itself put patients at higher risk for limb loss because severe infection increases the risk of blood clots, but patients with diabetes appear to have been far more likely to undergo any level of amputation during the pandemic than before it began.

In a study of patients with diabetes attending a foot and ankle surgery service in Ohio, the risk of having any level of amputation was 10.8 times higher during compared with before the pandemic. And of patients undergoing any amputation, the odds for receiving a major amputation was 3.1 times higher than before the pandemic.

Telehealth and web-based options for diabetes care and education could help improve health outcomes, particularly during lockdowns.

“Having a diabetes-related amputation is life-changing – it brings disability and functional limitations to the individual – and within the health care system, it reflects the failure of secondary prevention efforts, which ideally should slow the progression of diabetic complications,” noted Dr. Akinlotan.
 

Race and geography affect risk of amputation

In their study, Dr. Akinlotan and colleagues used data from the National Inpatient Sample to identify trends in LEAs among patients primarily hospitalized for diabetes in the United States between 2009 and 2017.

“The primary outcome variable was documentation of either minor or major LEA during a diabetes-related admission,” they explain.

Minor LEAs increased significantly across all ethnic groups.

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

Rates of minor diabetes-related lower extremity amputations (LEAs) in hospitalized patients increased between 2009 and 2017 in all racial and ethnic groups, in both rural and urban areas, and in all geographic regions across the United States, a new retrospective, observational study indicates.

In contrast, major lower extremity amputation rates held steady during the study period with a few exceptions.

There was also a decline in major-to-minor amputation ratios, especially among Native Americans – a sign that diabetes was being better managed and foot ulcers were being caught earlier, preventing the need for a major amputation above the foot or below or above the knee.

Minor LEAs include the loss of a toe, toes, or a foot.

“While I know an amputation is devastating either way, having a minor amputation is better than having a major amputation, and trends [at least to 2017] show that comprehensive foot examinations are paying off,” lead author Marvellous Akinlotan, PhD, MPH, a research associate at the Southwest Rural Health Research Center in Bryan, Texas, said in an interview.

Asked to comment, Marcia Ory, PhD, MPH, director of the Center for Population Health & Aging, Texas A&M School of Public Health, College Station, who was not involved in the study, said: “It points to some successes, but it also points to the need for continued education and preventive care to reduce all types of amputations.”

The study was published online in Diabetes Care.
 

Amputations increased during COVID-19

However, the study was conducted prior to the COVID-19 pandemic, and amputation rates appear to have significantly worsened during the past 18 months.

In a summary of recent evidence collated by the Amputee Coalition, the authors point out that not only does COVID-19 itself put patients at higher risk for limb loss because severe infection increases the risk of blood clots, but patients with diabetes appear to have been far more likely to undergo any level of amputation during the pandemic than before it began.

In a study of patients with diabetes attending a foot and ankle surgery service in Ohio, the risk of having any level of amputation was 10.8 times higher during compared with before the pandemic. And of patients undergoing any amputation, the odds for receiving a major amputation was 3.1 times higher than before the pandemic.

Telehealth and web-based options for diabetes care and education could help improve health outcomes, particularly during lockdowns.

“Having a diabetes-related amputation is life-changing – it brings disability and functional limitations to the individual – and within the health care system, it reflects the failure of secondary prevention efforts, which ideally should slow the progression of diabetic complications,” noted Dr. Akinlotan.
 

Race and geography affect risk of amputation

In their study, Dr. Akinlotan and colleagues used data from the National Inpatient Sample to identify trends in LEAs among patients primarily hospitalized for diabetes in the United States between 2009 and 2017.

“The primary outcome variable was documentation of either minor or major LEA during a diabetes-related admission,” they explain.

Minor LEAs increased significantly across all ethnic groups.

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

Rates of minor diabetes-related lower extremity amputations (LEAs) in hospitalized patients increased between 2009 and 2017 in all racial and ethnic groups, in both rural and urban areas, and in all geographic regions across the United States, a new retrospective, observational study indicates.

In contrast, major lower extremity amputation rates held steady during the study period with a few exceptions.

There was also a decline in major-to-minor amputation ratios, especially among Native Americans – a sign that diabetes was being better managed and foot ulcers were being caught earlier, preventing the need for a major amputation above the foot or below or above the knee.

Minor LEAs include the loss of a toe, toes, or a foot.

“While I know an amputation is devastating either way, having a minor amputation is better than having a major amputation, and trends [at least to 2017] show that comprehensive foot examinations are paying off,” lead author Marvellous Akinlotan, PhD, MPH, a research associate at the Southwest Rural Health Research Center in Bryan, Texas, said in an interview.

Asked to comment, Marcia Ory, PhD, MPH, director of the Center for Population Health & Aging, Texas A&M School of Public Health, College Station, who was not involved in the study, said: “It points to some successes, but it also points to the need for continued education and preventive care to reduce all types of amputations.”

The study was published online in Diabetes Care.
 

Amputations increased during COVID-19

However, the study was conducted prior to the COVID-19 pandemic, and amputation rates appear to have significantly worsened during the past 18 months.

In a summary of recent evidence collated by the Amputee Coalition, the authors point out that not only does COVID-19 itself put patients at higher risk for limb loss because severe infection increases the risk of blood clots, but patients with diabetes appear to have been far more likely to undergo any level of amputation during the pandemic than before it began.

In a study of patients with diabetes attending a foot and ankle surgery service in Ohio, the risk of having any level of amputation was 10.8 times higher during compared with before the pandemic. And of patients undergoing any amputation, the odds for receiving a major amputation was 3.1 times higher than before the pandemic.

Telehealth and web-based options for diabetes care and education could help improve health outcomes, particularly during lockdowns.

“Having a diabetes-related amputation is life-changing – it brings disability and functional limitations to the individual – and within the health care system, it reflects the failure of secondary prevention efforts, which ideally should slow the progression of diabetic complications,” noted Dr. Akinlotan.
 

Race and geography affect risk of amputation

In their study, Dr. Akinlotan and colleagues used data from the National Inpatient Sample to identify trends in LEAs among patients primarily hospitalized for diabetes in the United States between 2009 and 2017.

“The primary outcome variable was documentation of either minor or major LEA during a diabetes-related admission,” they explain.

Minor LEAs increased significantly across all ethnic groups.

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

It was a typical, busy evening shift in the emergency department (ED) when Steve Carroll, DO, an emergency medicine physician in the Philadelphia area, noticed an odd listing on the tracking board. In the waiting room, there was someone whose chief complaint was that she needed to have surgical drains pulled.

According to the woman’s chart, she’d undergone liposuction in Miami a week before. She came bearing a letter from her surgeon to an ED physician with specific instructions on when and how to remove the drains. The surgeon had effectively relinquished all follow-up care to the woman’s local ED.

Dr. Carroll searched the name of her surgeon and found that his site “specifically advertised medical tourism,” Dr. Carroll said. The site lured patients with the idea of recovering by the beach and that a local nurse would come to their room every day.

But when Dr. Carroll told the patient that her surgeon should be the one who removes the drains, she became concerned. She didn’t know that her surgeon wasn’t providing the standard of care, he said. Somewhat appalled that a board-certified plastic surgeon would place the burden of follow-up care on an ED doctor hundreds of miles away, Dr. Carroll posted the case to Twitter and several Facebook groups.

“Yes I could refuse to take [the drains] out but that’s not patient-centered care,” Dr. Carroll wrote in a Twitter thread. “It’s unfairly shifting routine outpatient surgical followup (and liability) onto me and extra cost to [the patient].” Comments from ED physicians and sympathetic surgeons across the country flowed in. Dr. Carroll quickly realized his situation was part of a much larger problem than he’d thought.

Dr. Carroll’s patient told him that the Miami surgery cost less than undergoing the surgery locally; that’s why she’d made the trip. She’s not alone. Traveling to get the lowest price for a plastic surgery procedure has been a rising phenomenon since the early 2000s, according to the American Society of Plastic Surgeons (ASPS). Many countries are actively fostering their medical tourism industries, as are states such as Florida.

People have long traveled to get the best medical care. But “medical tourism is completely different,” said Alan Matarasso, MD, FACS, a Manhattan-based plastic surgeon and member of the ASPS Executive Committee. “People [are] traveling to get a simultaneous vacation or lower cost,” he said.

Choosing facilities on the basis of these criteria comes with myriad problems, and the quality of medical care may be lower. It’s difficult to verify the credentials of the surgeons, anesthesiologists, and facilities involved. Medical records can be in a different language, and traveling immediately after surgery increases the risk for pulmonary embolism and death, not to mention the added complications of traveling and being a surgical patient during the COVID-19 pandemic, he said.

Typically, surgeons are protective of their patients. But Murtaza Akhter, MD, an emergency medicine physician based in Miami, says it’s the opposite with the medical tourism surgeons whose patients regularly end up in his ED. “There’s almost no ownership,” he said. “Every time, [the patients] say, ‘My doctor isn’t responding,’ or they said go to the ER.” And that’s before they’ve even made it out of Miami.

The most common cosmetic surgery complications Dr. Akhter sees occur in patients who’ve undergone so-called Brazilian butt lifts. They show up in his ED face down, suffering from severe blood loss. He has them undergo a transfusion and maybe some imaging, but if they need a higher degree of care, they have to be transferred. “There’s a reason it’s cheaper,” he said.

Medical tourism mishaps are such a regular occurrence in Miami that no one flinches when the patients show up in the ED, Dr. Akhter said. He had begun to think he was overreacting to the problem until he saw Dr. Carroll’s Twitter thread.

“Since it’s daily, I just thought maybe I had gone crazy and that it’s considered normal for plastic surgeons to do this. Thanks for making me feel sane again,” Dr. Akhter tweeted in a reply to Dr. Carroll.

There are no reliable data as to of how often or where such surgeries are occurring or of patients’ outcomes. But Nicholas Genes, MD, an ED physician in Manhattan, says he sees far more postsurgical patients who traveled for their procedures than ones who underwent surgery locally. He can’t say for certain whether that’s because procedures performed by doctors in New York City have fewer complications or the physicians just handle postprocedure problems themselves.

In a 2021 systematic review of aesthetic breast surgeries performed through medical tourism, researchers found that of 171 patients who traveled for surgery, 88 (51%) had a total of 106 complications that required returning to the operating room and undergoing general anesthesia. They also found that 39% of breast augmentation implant surgeries required either a unilateral or bilateral explantation procedure after patients returned home.

The rate of complications was higher than the study authors had expected. “These are totally elective procedures,” Dr. Matarasso said. “They should be optimized.” And high rates of complications come with hefty price tags.

The cost of managing these complications, which falls to the home healthcare system or the patient themselves, can range from $5,500 (determined on the basis of data from a 2019 study in the United Kingdom) to as much as $123,000, researchers in New York City calculated, if the patient develops a complicated mycobacterium infection.

“In your effort to get a good deal or around the system, you could still end up with a lot of extensive medical bills if something goes wrong,” Dr. Genes said.
 

The liability dilemma

Many of the ED physicians Dr. Carroll heard from said that they wouldn’t have treated the woman who needed to have drains removed. Unlike the Brazilian-butt-lifts-gone-wrong in Miami or the complications Dr. Genes sees in New York City, Dr. Carroll’s patient wasn’t in a state of emergency. Most ED physicians said they would have sent her on her way to find a surgeon.

“In general, we shouldn’t be doing things we aren’t trained to do. It’s sort of a slippery slope,” Dr. Genes said. He’s comfortable with removing stitches, but for surgical drains and plastic apparatuses, “I don’t feel particularly well trained. I’d have to consult a colleague in general surgery,” he said. When he does get one of these patients, he works the phones to find a plastic surgeon who will see the patient, something he says their original plastic surgeon should have done.

“Sitting there with the patient, I felt a little bad for her,” Dr. Carroll said. “I knew if I didn’t do it, it would be weeks while she bounced around to urgent care, primary care, and finally found a surgeon.” But by removing the drains, he did shift some of the liability to himself. “If she developed a wound infection, then I’m on the hook for [that],” he said. “If I send her away, I have less liability but didn’t quite do the right thing for the patient.”

In replies to Dr. Carroll’s thread, some doctors debated whether these types of cases, particularly those in which surgeons forgo follow-up care, could be considered medical abandonment. Legal experts say that’s not exactly the case, at least it would not be the case with Dr. Carroll’s patient.

“I don’t think they’ve abandoned the patient; I think they’ve abandoned care,” said Michael Flynn, JD, professor of personal injury law at Nova Southeastern University, in Fort Lauderdale–Davie, Fla. “And that abandonment of follow-up care, if it falls below the standard of what medical professionals should do, then it’s malpractice.”

“The doctor didn’t just walk away and become unreachable,” said Bernard Black, JD, a medical malpractice attorney and law professor at Northwestern University, in Evanston, Ill. Technically, the surgeon referred the patient to the ED. Mr. Black agreed that it sounds more like a question of malpractice, “but without real damages, there’s no claim.”

Even if not illegal, sending these patients to the ED is still highly unethical, Dr. Carroll said. The authors of a 2014 article in Aesthetic Plastic Surgery concur: “It is the duty and ethical responsibility of plastic surgeons to prevent unnecessary complications following tourism medicine by adequately counseling patients, defining perioperative treatment protocols, and reporting complications to regional and specialty-specific governing bodies,” they write.

Sometimes patients need to travel, Dr. Matarasso said. Recently, three out-of-state patients came to him for procedures. Two stayed in Manhattan until their follow-up care was finished; he arranged care elsewhere for the third. It’s the operating surgeon’s job to connect patients with someone who can provide follow-up care when they go home, Dr. Matarasso said. If a surgeon doesn’t have a connection in a patient’s home city, the ASPS has a referral service to help, he said.

“My frustration was never with the patient,” Dr. Carroll said. “No one should feel bad about coming to an ED for literally anything, and I mean that. My frustration is with the surgeon who didn’t go the one extra step to arrange her follow-up.”

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

It was a typical, busy evening shift in the emergency department (ED) when Steve Carroll, DO, an emergency medicine physician in the Philadelphia area, noticed an odd listing on the tracking board. In the waiting room, there was someone whose chief complaint was that she needed to have surgical drains pulled.

According to the woman’s chart, she’d undergone liposuction in Miami a week before. She came bearing a letter from her surgeon to an ED physician with specific instructions on when and how to remove the drains. The surgeon had effectively relinquished all follow-up care to the woman’s local ED.

Dr. Carroll searched the name of her surgeon and found that his site “specifically advertised medical tourism,” Dr. Carroll said. The site lured patients with the idea of recovering by the beach and that a local nurse would come to their room every day.

But when Dr. Carroll told the patient that her surgeon should be the one who removes the drains, she became concerned. She didn’t know that her surgeon wasn’t providing the standard of care, he said. Somewhat appalled that a board-certified plastic surgeon would place the burden of follow-up care on an ED doctor hundreds of miles away, Dr. Carroll posted the case to Twitter and several Facebook groups.

“Yes I could refuse to take [the drains] out but that’s not patient-centered care,” Dr. Carroll wrote in a Twitter thread. “It’s unfairly shifting routine outpatient surgical followup (and liability) onto me and extra cost to [the patient].” Comments from ED physicians and sympathetic surgeons across the country flowed in. Dr. Carroll quickly realized his situation was part of a much larger problem than he’d thought.

Dr. Carroll’s patient told him that the Miami surgery cost less than undergoing the surgery locally; that’s why she’d made the trip. She’s not alone. Traveling to get the lowest price for a plastic surgery procedure has been a rising phenomenon since the early 2000s, according to the American Society of Plastic Surgeons (ASPS). Many countries are actively fostering their medical tourism industries, as are states such as Florida.

People have long traveled to get the best medical care. But “medical tourism is completely different,” said Alan Matarasso, MD, FACS, a Manhattan-based plastic surgeon and member of the ASPS Executive Committee. “People [are] traveling to get a simultaneous vacation or lower cost,” he said.

Choosing facilities on the basis of these criteria comes with myriad problems, and the quality of medical care may be lower. It’s difficult to verify the credentials of the surgeons, anesthesiologists, and facilities involved. Medical records can be in a different language, and traveling immediately after surgery increases the risk for pulmonary embolism and death, not to mention the added complications of traveling and being a surgical patient during the COVID-19 pandemic, he said.

Typically, surgeons are protective of their patients. But Murtaza Akhter, MD, an emergency medicine physician based in Miami, says it’s the opposite with the medical tourism surgeons whose patients regularly end up in his ED. “There’s almost no ownership,” he said. “Every time, [the patients] say, ‘My doctor isn’t responding,’ or they said go to the ER.” And that’s before they’ve even made it out of Miami.

The most common cosmetic surgery complications Dr. Akhter sees occur in patients who’ve undergone so-called Brazilian butt lifts. They show up in his ED face down, suffering from severe blood loss. He has them undergo a transfusion and maybe some imaging, but if they need a higher degree of care, they have to be transferred. “There’s a reason it’s cheaper,” he said.

Medical tourism mishaps are such a regular occurrence in Miami that no one flinches when the patients show up in the ED, Dr. Akhter said. He had begun to think he was overreacting to the problem until he saw Dr. Carroll’s Twitter thread.

“Since it’s daily, I just thought maybe I had gone crazy and that it’s considered normal for plastic surgeons to do this. Thanks for making me feel sane again,” Dr. Akhter tweeted in a reply to Dr. Carroll.

There are no reliable data as to of how often or where such surgeries are occurring or of patients’ outcomes. But Nicholas Genes, MD, an ED physician in Manhattan, says he sees far more postsurgical patients who traveled for their procedures than ones who underwent surgery locally. He can’t say for certain whether that’s because procedures performed by doctors in New York City have fewer complications or the physicians just handle postprocedure problems themselves.

In a 2021 systematic review of aesthetic breast surgeries performed through medical tourism, researchers found that of 171 patients who traveled for surgery, 88 (51%) had a total of 106 complications that required returning to the operating room and undergoing general anesthesia. They also found that 39% of breast augmentation implant surgeries required either a unilateral or bilateral explantation procedure after patients returned home.

The rate of complications was higher than the study authors had expected. “These are totally elective procedures,” Dr. Matarasso said. “They should be optimized.” And high rates of complications come with hefty price tags.

The cost of managing these complications, which falls to the home healthcare system or the patient themselves, can range from $5,500 (determined on the basis of data from a 2019 study in the United Kingdom) to as much as $123,000, researchers in New York City calculated, if the patient develops a complicated mycobacterium infection.

“In your effort to get a good deal or around the system, you could still end up with a lot of extensive medical bills if something goes wrong,” Dr. Genes said.
 

The liability dilemma

Many of the ED physicians Dr. Carroll heard from said that they wouldn’t have treated the woman who needed to have drains removed. Unlike the Brazilian-butt-lifts-gone-wrong in Miami or the complications Dr. Genes sees in New York City, Dr. Carroll’s patient wasn’t in a state of emergency. Most ED physicians said they would have sent her on her way to find a surgeon.

“In general, we shouldn’t be doing things we aren’t trained to do. It’s sort of a slippery slope,” Dr. Genes said. He’s comfortable with removing stitches, but for surgical drains and plastic apparatuses, “I don’t feel particularly well trained. I’d have to consult a colleague in general surgery,” he said. When he does get one of these patients, he works the phones to find a plastic surgeon who will see the patient, something he says their original plastic surgeon should have done.

“Sitting there with the patient, I felt a little bad for her,” Dr. Carroll said. “I knew if I didn’t do it, it would be weeks while she bounced around to urgent care, primary care, and finally found a surgeon.” But by removing the drains, he did shift some of the liability to himself. “If she developed a wound infection, then I’m on the hook for [that],” he said. “If I send her away, I have less liability but didn’t quite do the right thing for the patient.”

In replies to Dr. Carroll’s thread, some doctors debated whether these types of cases, particularly those in which surgeons forgo follow-up care, could be considered medical abandonment. Legal experts say that’s not exactly the case, at least it would not be the case with Dr. Carroll’s patient.

“I don’t think they’ve abandoned the patient; I think they’ve abandoned care,” said Michael Flynn, JD, professor of personal injury law at Nova Southeastern University, in Fort Lauderdale–Davie, Fla. “And that abandonment of follow-up care, if it falls below the standard of what medical professionals should do, then it’s malpractice.”

“The doctor didn’t just walk away and become unreachable,” said Bernard Black, JD, a medical malpractice attorney and law professor at Northwestern University, in Evanston, Ill. Technically, the surgeon referred the patient to the ED. Mr. Black agreed that it sounds more like a question of malpractice, “but without real damages, there’s no claim.”

Even if not illegal, sending these patients to the ED is still highly unethical, Dr. Carroll said. The authors of a 2014 article in Aesthetic Plastic Surgery concur: “It is the duty and ethical responsibility of plastic surgeons to prevent unnecessary complications following tourism medicine by adequately counseling patients, defining perioperative treatment protocols, and reporting complications to regional and specialty-specific governing bodies,” they write.

Sometimes patients need to travel, Dr. Matarasso said. Recently, three out-of-state patients came to him for procedures. Two stayed in Manhattan until their follow-up care was finished; he arranged care elsewhere for the third. It’s the operating surgeon’s job to connect patients with someone who can provide follow-up care when they go home, Dr. Matarasso said. If a surgeon doesn’t have a connection in a patient’s home city, the ASPS has a referral service to help, he said.

“My frustration was never with the patient,” Dr. Carroll said. “No one should feel bad about coming to an ED for literally anything, and I mean that. My frustration is with the surgeon who didn’t go the one extra step to arrange her follow-up.”

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

It was a typical, busy evening shift in the emergency department (ED) when Steve Carroll, DO, an emergency medicine physician in the Philadelphia area, noticed an odd listing on the tracking board. In the waiting room, there was someone whose chief complaint was that she needed to have surgical drains pulled.

According to the woman’s chart, she’d undergone liposuction in Miami a week before. She came bearing a letter from her surgeon to an ED physician with specific instructions on when and how to remove the drains. The surgeon had effectively relinquished all follow-up care to the woman’s local ED.

Dr. Carroll searched the name of her surgeon and found that his site “specifically advertised medical tourism,” Dr. Carroll said. The site lured patients with the idea of recovering by the beach and that a local nurse would come to their room every day.

But when Dr. Carroll told the patient that her surgeon should be the one who removes the drains, she became concerned. She didn’t know that her surgeon wasn’t providing the standard of care, he said. Somewhat appalled that a board-certified plastic surgeon would place the burden of follow-up care on an ED doctor hundreds of miles away, Dr. Carroll posted the case to Twitter and several Facebook groups.

“Yes I could refuse to take [the drains] out but that’s not patient-centered care,” Dr. Carroll wrote in a Twitter thread. “It’s unfairly shifting routine outpatient surgical followup (and liability) onto me and extra cost to [the patient].” Comments from ED physicians and sympathetic surgeons across the country flowed in. Dr. Carroll quickly realized his situation was part of a much larger problem than he’d thought.

Dr. Carroll’s patient told him that the Miami surgery cost less than undergoing the surgery locally; that’s why she’d made the trip. She’s not alone. Traveling to get the lowest price for a plastic surgery procedure has been a rising phenomenon since the early 2000s, according to the American Society of Plastic Surgeons (ASPS). Many countries are actively fostering their medical tourism industries, as are states such as Florida.

People have long traveled to get the best medical care. But “medical tourism is completely different,” said Alan Matarasso, MD, FACS, a Manhattan-based plastic surgeon and member of the ASPS Executive Committee. “People [are] traveling to get a simultaneous vacation or lower cost,” he said.

Choosing facilities on the basis of these criteria comes with myriad problems, and the quality of medical care may be lower. It’s difficult to verify the credentials of the surgeons, anesthesiologists, and facilities involved. Medical records can be in a different language, and traveling immediately after surgery increases the risk for pulmonary embolism and death, not to mention the added complications of traveling and being a surgical patient during the COVID-19 pandemic, he said.

Typically, surgeons are protective of their patients. But Murtaza Akhter, MD, an emergency medicine physician based in Miami, says it’s the opposite with the medical tourism surgeons whose patients regularly end up in his ED. “There’s almost no ownership,” he said. “Every time, [the patients] say, ‘My doctor isn’t responding,’ or they said go to the ER.” And that’s before they’ve even made it out of Miami.

The most common cosmetic surgery complications Dr. Akhter sees occur in patients who’ve undergone so-called Brazilian butt lifts. They show up in his ED face down, suffering from severe blood loss. He has them undergo a transfusion and maybe some imaging, but if they need a higher degree of care, they have to be transferred. “There’s a reason it’s cheaper,” he said.

Medical tourism mishaps are such a regular occurrence in Miami that no one flinches when the patients show up in the ED, Dr. Akhter said. He had begun to think he was overreacting to the problem until he saw Dr. Carroll’s Twitter thread.

“Since it’s daily, I just thought maybe I had gone crazy and that it’s considered normal for plastic surgeons to do this. Thanks for making me feel sane again,” Dr. Akhter tweeted in a reply to Dr. Carroll.

There are no reliable data as to of how often or where such surgeries are occurring or of patients’ outcomes. But Nicholas Genes, MD, an ED physician in Manhattan, says he sees far more postsurgical patients who traveled for their procedures than ones who underwent surgery locally. He can’t say for certain whether that’s because procedures performed by doctors in New York City have fewer complications or the physicians just handle postprocedure problems themselves.

In a 2021 systematic review of aesthetic breast surgeries performed through medical tourism, researchers found that of 171 patients who traveled for surgery, 88 (51%) had a total of 106 complications that required returning to the operating room and undergoing general anesthesia. They also found that 39% of breast augmentation implant surgeries required either a unilateral or bilateral explantation procedure after patients returned home.

The rate of complications was higher than the study authors had expected. “These are totally elective procedures,” Dr. Matarasso said. “They should be optimized.” And high rates of complications come with hefty price tags.

The cost of managing these complications, which falls to the home healthcare system or the patient themselves, can range from $5,500 (determined on the basis of data from a 2019 study in the United Kingdom) to as much as $123,000, researchers in New York City calculated, if the patient develops a complicated mycobacterium infection.

“In your effort to get a good deal or around the system, you could still end up with a lot of extensive medical bills if something goes wrong,” Dr. Genes said.
 

The liability dilemma

Many of the ED physicians Dr. Carroll heard from said that they wouldn’t have treated the woman who needed to have drains removed. Unlike the Brazilian-butt-lifts-gone-wrong in Miami or the complications Dr. Genes sees in New York City, Dr. Carroll’s patient wasn’t in a state of emergency. Most ED physicians said they would have sent her on her way to find a surgeon.

“In general, we shouldn’t be doing things we aren’t trained to do. It’s sort of a slippery slope,” Dr. Genes said. He’s comfortable with removing stitches, but for surgical drains and plastic apparatuses, “I don’t feel particularly well trained. I’d have to consult a colleague in general surgery,” he said. When he does get one of these patients, he works the phones to find a plastic surgeon who will see the patient, something he says their original plastic surgeon should have done.

“Sitting there with the patient, I felt a little bad for her,” Dr. Carroll said. “I knew if I didn’t do it, it would be weeks while she bounced around to urgent care, primary care, and finally found a surgeon.” But by removing the drains, he did shift some of the liability to himself. “If she developed a wound infection, then I’m on the hook for [that],” he said. “If I send her away, I have less liability but didn’t quite do the right thing for the patient.”

In replies to Dr. Carroll’s thread, some doctors debated whether these types of cases, particularly those in which surgeons forgo follow-up care, could be considered medical abandonment. Legal experts say that’s not exactly the case, at least it would not be the case with Dr. Carroll’s patient.

“I don’t think they’ve abandoned the patient; I think they’ve abandoned care,” said Michael Flynn, JD, professor of personal injury law at Nova Southeastern University, in Fort Lauderdale–Davie, Fla. “And that abandonment of follow-up care, if it falls below the standard of what medical professionals should do, then it’s malpractice.”

“The doctor didn’t just walk away and become unreachable,” said Bernard Black, JD, a medical malpractice attorney and law professor at Northwestern University, in Evanston, Ill. Technically, the surgeon referred the patient to the ED. Mr. Black agreed that it sounds more like a question of malpractice, “but without real damages, there’s no claim.”

Even if not illegal, sending these patients to the ED is still highly unethical, Dr. Carroll said. The authors of a 2014 article in Aesthetic Plastic Surgery concur: “It is the duty and ethical responsibility of plastic surgeons to prevent unnecessary complications following tourism medicine by adequately counseling patients, defining perioperative treatment protocols, and reporting complications to regional and specialty-specific governing bodies,” they write.

Sometimes patients need to travel, Dr. Matarasso said. Recently, three out-of-state patients came to him for procedures. Two stayed in Manhattan until their follow-up care was finished; he arranged care elsewhere for the third. It’s the operating surgeon’s job to connect patients with someone who can provide follow-up care when they go home, Dr. Matarasso said. If a surgeon doesn’t have a connection in a patient’s home city, the ASPS has a referral service to help, he said.

“My frustration was never with the patient,” Dr. Carroll said. “No one should feel bad about coming to an ED for literally anything, and I mean that. My frustration is with the surgeon who didn’t go the one extra step to arrange her follow-up.”

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

From mid-December 2020 through early May 2021, there were 139,393 fewer deaths from COVID-19 and about 3.1 million fewer confirmed cases in the United States than would have been expected without the COVID-19 vaccination campaign, finds a new report published online in Health Affairs.

New York had 11.7 fewer COVID-19 deaths per 10,000 adults, and Hawaii had 1.1 fewer deaths per 10,000 than would have occurred without vaccinations, the study shows. The rest of the states fell somewhere in between, with the average state experiencing five fewer COVID-19 deaths per 10,000 adults.

At a national level, this means that instead of the 550,000 COVID-19 deaths that occurred by early May, there would have been 709,000 deaths in the absence of a vaccination campaign, according to the study.

Researchers from RAND and Indiana University created models to estimate the number of COVID-19 deaths that would have happened without vaccinations. The difference between the actual number of deaths and those estimates provides a measure of the number of COVID-19 deaths averted by the vaccination campaign.

Information about vaccine doses administered in each state came from the Bloomberg COVID-19 Vaccine Tracker, and data on COVID-19 deaths for each state came from The New York Times’ Coronavirus (COVID-19) Data in the United States database.

The study spanned the period from Dec. 21, 2020 to May 9, 2021. The U.S. Food and Drug Administration issued its first emergency use authorization (EUA) for a COVID-19 vaccine to Pfizer/BioNTech on December 11, followed by an EUA for the Moderna vaccine on December 18 and one for Johnson & Johnson’s vaccine on Feb. 27, 2021.
 

Varied by state

There were wide variations in the speed and extent of the vaccination campaigns in various states, the researchers found. For example, West Virginia was the first state to reach 10 doses per 100 adults, reaching that goal on Jan. 16, 2021, and Idaho was the last state to hit that mark, on Feb. 4, 2021. Alaska was the first to reach 20 doses per 100 adults, on January 29, and Alabama was the last to do it, on February 21.

On May 6, California was the first state to administer 120 doses per 100 adults, but many states have still not reached that milestone.

The median number of days between the milestones of 10 and 20 doses per 100 adults was 19 days, and the median number of days between 20 and 40 doses per 100 adults was 24 days.
 

Hard to establish causality

The researchers emphasized that “establishment of causality is challenging” in comparing individual states’ vaccination levels with their COVID-19 mortality rates.

Aside from the study being observational, they pointed out, the analysis “relied on variation in the administration of COVID-19 vaccines across states … Vaccine administration patterns may be associated with declining mortality because of vaccine prevention of deaths and severe complications as state-level vaccine campaigns allocated initial doses to the highest-risk populations with the aim of immediately reducing COVID-19 deaths.”

Nevertheless, the authors note, “clinical trial evidence has shown that COVID-19 vaccines have high efficacy. Our study provides support for policies that further expand vaccine administration, which will enable larger populations to benefit.”
 

Study confirms vaccine benefit

Aaron Glatt, MD, chair of medicine at Mount Sinai South Nassau in Oceanside, New York, and a spokesman for the Infectious Disease Society of America, said in an interview that the study is important because it confirms the benefit of COVID-19 vaccination.

Regardless of whether the study’s results are statistically valid, he said, “I don’t think anyone can argue the benefit isn’t there. It’s a question of how important the benefit is.”

Dr. Glatt is not surprised that there are variations across states in the number of COVID-19 deaths averted through vaccination. “Clearly, in states where there was a lot of disease, a significant amount of vaccination is going to impact that tremendously.”

The authors note that their paper has some limitations. For one thing, they couldn’t determine what share of the estimated reduction in COVID-19 deaths was a result of the proportion of the population that was vaccinated or had antibodies and what share was a result of lower population-level risk for COVID-19 transmission.
 

Vaccination versus natural immunity

In addition, the researchers weren’t able to identify the roles of vaccination, natural immunity, and changes in mobility in the numbers of COVID-19 deaths.

Dr. Glatt says that’s understandable, since this was a retrospective study, and the researchers didn’t know how many people had been infected with COVID-19 at some point. Moreover, he adds, scientists don’t know how strong natural immunity from prior infection is, how long it endures, or how robust it is against new variants.

“It’s clear to me that there’s a benefit in preventing the second episode of COVID in people who had a first episode of COVID,” he said. “What we don’t know is how much that benefit is and how long it will last.”

The researchers also didn’t know how many people had gotten both doses of the Pfizer or the Moderna vaccine and how many of them had received only one. This is an important piece of information, Dr. Glatt said, but the lack of it doesn’t impair the study’s overall finding.

“Every vaccine potentially prevents death,” he stressed. “The more we vaccinate, the more deaths we’ll prevent. We’re starting to see increased vaccinations again. There were a million of them yesterday. So people are recognizing that COVID hasn’t gone away, and we need to vaccinate more people. The benefit from the vaccination hasn’t decreased. The more we vaccinate, the more the benefit will be.”

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

From mid-December 2020 through early May 2021, there were 139,393 fewer deaths from COVID-19 and about 3.1 million fewer confirmed cases in the United States than would have been expected without the COVID-19 vaccination campaign, finds a new report published online in Health Affairs.

New York had 11.7 fewer COVID-19 deaths per 10,000 adults, and Hawaii had 1.1 fewer deaths per 10,000 than would have occurred without vaccinations, the study shows. The rest of the states fell somewhere in between, with the average state experiencing five fewer COVID-19 deaths per 10,000 adults.

At a national level, this means that instead of the 550,000 COVID-19 deaths that occurred by early May, there would have been 709,000 deaths in the absence of a vaccination campaign, according to the study.

Researchers from RAND and Indiana University created models to estimate the number of COVID-19 deaths that would have happened without vaccinations. The difference between the actual number of deaths and those estimates provides a measure of the number of COVID-19 deaths averted by the vaccination campaign.

Information about vaccine doses administered in each state came from the Bloomberg COVID-19 Vaccine Tracker, and data on COVID-19 deaths for each state came from The New York Times’ Coronavirus (COVID-19) Data in the United States database.

The study spanned the period from Dec. 21, 2020 to May 9, 2021. The U.S. Food and Drug Administration issued its first emergency use authorization (EUA) for a COVID-19 vaccine to Pfizer/BioNTech on December 11, followed by an EUA for the Moderna vaccine on December 18 and one for Johnson & Johnson’s vaccine on Feb. 27, 2021.
 

Varied by state

There were wide variations in the speed and extent of the vaccination campaigns in various states, the researchers found. For example, West Virginia was the first state to reach 10 doses per 100 adults, reaching that goal on Jan. 16, 2021, and Idaho was the last state to hit that mark, on Feb. 4, 2021. Alaska was the first to reach 20 doses per 100 adults, on January 29, and Alabama was the last to do it, on February 21.

On May 6, California was the first state to administer 120 doses per 100 adults, but many states have still not reached that milestone.

The median number of days between the milestones of 10 and 20 doses per 100 adults was 19 days, and the median number of days between 20 and 40 doses per 100 adults was 24 days.
 

Hard to establish causality

The researchers emphasized that “establishment of causality is challenging” in comparing individual states’ vaccination levels with their COVID-19 mortality rates.

Aside from the study being observational, they pointed out, the analysis “relied on variation in the administration of COVID-19 vaccines across states … Vaccine administration patterns may be associated with declining mortality because of vaccine prevention of deaths and severe complications as state-level vaccine campaigns allocated initial doses to the highest-risk populations with the aim of immediately reducing COVID-19 deaths.”

Nevertheless, the authors note, “clinical trial evidence has shown that COVID-19 vaccines have high efficacy. Our study provides support for policies that further expand vaccine administration, which will enable larger populations to benefit.”
 

Study confirms vaccine benefit

Aaron Glatt, MD, chair of medicine at Mount Sinai South Nassau in Oceanside, New York, and a spokesman for the Infectious Disease Society of America, said in an interview that the study is important because it confirms the benefit of COVID-19 vaccination.

Regardless of whether the study’s results are statistically valid, he said, “I don’t think anyone can argue the benefit isn’t there. It’s a question of how important the benefit is.”

Dr. Glatt is not surprised that there are variations across states in the number of COVID-19 deaths averted through vaccination. “Clearly, in states where there was a lot of disease, a significant amount of vaccination is going to impact that tremendously.”

The authors note that their paper has some limitations. For one thing, they couldn’t determine what share of the estimated reduction in COVID-19 deaths was a result of the proportion of the population that was vaccinated or had antibodies and what share was a result of lower population-level risk for COVID-19 transmission.
 

Vaccination versus natural immunity

In addition, the researchers weren’t able to identify the roles of vaccination, natural immunity, and changes in mobility in the numbers of COVID-19 deaths.

Dr. Glatt says that’s understandable, since this was a retrospective study, and the researchers didn’t know how many people had been infected with COVID-19 at some point. Moreover, he adds, scientists don’t know how strong natural immunity from prior infection is, how long it endures, or how robust it is against new variants.

“It’s clear to me that there’s a benefit in preventing the second episode of COVID in people who had a first episode of COVID,” he said. “What we don’t know is how much that benefit is and how long it will last.”

The researchers also didn’t know how many people had gotten both doses of the Pfizer or the Moderna vaccine and how many of them had received only one. This is an important piece of information, Dr. Glatt said, but the lack of it doesn’t impair the study’s overall finding.

“Every vaccine potentially prevents death,” he stressed. “The more we vaccinate, the more deaths we’ll prevent. We’re starting to see increased vaccinations again. There were a million of them yesterday. So people are recognizing that COVID hasn’t gone away, and we need to vaccinate more people. The benefit from the vaccination hasn’t decreased. The more we vaccinate, the more the benefit will be.”

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

From mid-December 2020 through early May 2021, there were 139,393 fewer deaths from COVID-19 and about 3.1 million fewer confirmed cases in the United States than would have been expected without the COVID-19 vaccination campaign, finds a new report published online in Health Affairs.

New York had 11.7 fewer COVID-19 deaths per 10,000 adults, and Hawaii had 1.1 fewer deaths per 10,000 than would have occurred without vaccinations, the study shows. The rest of the states fell somewhere in between, with the average state experiencing five fewer COVID-19 deaths per 10,000 adults.

At a national level, this means that instead of the 550,000 COVID-19 deaths that occurred by early May, there would have been 709,000 deaths in the absence of a vaccination campaign, according to the study.

Researchers from RAND and Indiana University created models to estimate the number of COVID-19 deaths that would have happened without vaccinations. The difference between the actual number of deaths and those estimates provides a measure of the number of COVID-19 deaths averted by the vaccination campaign.

Information about vaccine doses administered in each state came from the Bloomberg COVID-19 Vaccine Tracker, and data on COVID-19 deaths for each state came from The New York Times’ Coronavirus (COVID-19) Data in the United States database.

The study spanned the period from Dec. 21, 2020 to May 9, 2021. The U.S. Food and Drug Administration issued its first emergency use authorization (EUA) for a COVID-19 vaccine to Pfizer/BioNTech on December 11, followed by an EUA for the Moderna vaccine on December 18 and one for Johnson & Johnson’s vaccine on Feb. 27, 2021.
 

Varied by state

There were wide variations in the speed and extent of the vaccination campaigns in various states, the researchers found. For example, West Virginia was the first state to reach 10 doses per 100 adults, reaching that goal on Jan. 16, 2021, and Idaho was the last state to hit that mark, on Feb. 4, 2021. Alaska was the first to reach 20 doses per 100 adults, on January 29, and Alabama was the last to do it, on February 21.

On May 6, California was the first state to administer 120 doses per 100 adults, but many states have still not reached that milestone.

The median number of days between the milestones of 10 and 20 doses per 100 adults was 19 days, and the median number of days between 20 and 40 doses per 100 adults was 24 days.
 

Hard to establish causality

The researchers emphasized that “establishment of causality is challenging” in comparing individual states’ vaccination levels with their COVID-19 mortality rates.

Aside from the study being observational, they pointed out, the analysis “relied on variation in the administration of COVID-19 vaccines across states … Vaccine administration patterns may be associated with declining mortality because of vaccine prevention of deaths and severe complications as state-level vaccine campaigns allocated initial doses to the highest-risk populations with the aim of immediately reducing COVID-19 deaths.”

Nevertheless, the authors note, “clinical trial evidence has shown that COVID-19 vaccines have high efficacy. Our study provides support for policies that further expand vaccine administration, which will enable larger populations to benefit.”
 

Study confirms vaccine benefit

Aaron Glatt, MD, chair of medicine at Mount Sinai South Nassau in Oceanside, New York, and a spokesman for the Infectious Disease Society of America, said in an interview that the study is important because it confirms the benefit of COVID-19 vaccination.

Regardless of whether the study’s results are statistically valid, he said, “I don’t think anyone can argue the benefit isn’t there. It’s a question of how important the benefit is.”

Dr. Glatt is not surprised that there are variations across states in the number of COVID-19 deaths averted through vaccination. “Clearly, in states where there was a lot of disease, a significant amount of vaccination is going to impact that tremendously.”

The authors note that their paper has some limitations. For one thing, they couldn’t determine what share of the estimated reduction in COVID-19 deaths was a result of the proportion of the population that was vaccinated or had antibodies and what share was a result of lower population-level risk for COVID-19 transmission.
 

Vaccination versus natural immunity

In addition, the researchers weren’t able to identify the roles of vaccination, natural immunity, and changes in mobility in the numbers of COVID-19 deaths.

Dr. Glatt says that’s understandable, since this was a retrospective study, and the researchers didn’t know how many people had been infected with COVID-19 at some point. Moreover, he adds, scientists don’t know how strong natural immunity from prior infection is, how long it endures, or how robust it is against new variants.

“It’s clear to me that there’s a benefit in preventing the second episode of COVID in people who had a first episode of COVID,” he said. “What we don’t know is how much that benefit is and how long it will last.”

The researchers also didn’t know how many people had gotten both doses of the Pfizer or the Moderna vaccine and how many of them had received only one. This is an important piece of information, Dr. Glatt said, but the lack of it doesn’t impair the study’s overall finding.

“Every vaccine potentially prevents death,” he stressed. “The more we vaccinate, the more deaths we’ll prevent. We’re starting to see increased vaccinations again. There were a million of them yesterday. So people are recognizing that COVID hasn’t gone away, and we need to vaccinate more people. The benefit from the vaccination hasn’t decreased. The more we vaccinate, the more the benefit will be.”

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

Among adults at high risk of type 2 diabetes – the leading cause of kidney disease – those who received vitamin D supplements as opposed to placebo for close to 3 years did not have significant differences in kidney function, in a secondary analysis of the Vitamin D and Type 2 Diabetes (D2d) study.

However, most of these adults with prediabetes plus obesity or overweight also had sufficient serum levels of 25-hydroxyvitamin D (25[OH]D) and a low risk for adverse kidney outcomes at study entry.

“The benefits of vitamin D might be greater in people with low blood vitamin D levels and/or reduced kidney function,” lead author Sun H. Kim, MD, Stanford (Calif.) University, speculated in a statement from the American Society of Nephrology.

The study was published online August 6 in the Clinical Journal of the American Society of Nephrology.

“The D2d study is unique because we recruited individuals with high-risk prediabetes, having two out of three abnormal glucose values, and we recruited more than 2,000 participants, representing the largest vitamin D diabetes prevention trial to date,” Dr. Kim pointed out.

Although the study did not show a benefit of vitamin D supplements on kidney function outcomes, 43% of participants were already taking up to 1,000 IU of vitamin D daily when they entered the study, she noted.

A subgroup analysis of individuals who were not taking vitamin D at study entry found that vitamin D supplements were associated with lowered proteinuria, “which means that it could have a beneficial effect on kidney health,” said Dr. Kim, cautioning that “additional studies are needed to look into this further.”
 

Effect of vitamin D on three kidney function outcomes

Although low levels of serum 25(OH)D are associated with kidney disease, few trials have evaluated how vitamin D supplements might affect kidney function, Dr. Kim and colleagues write.

The D2d trial, they note, found that vitamin D supplements did not lower the risk of incident diabetes in people with prediabetes recruited from medical centers across the United States, as previously reported in 2019.

However, since then, meta-analyses that included the D2d trial have reported a significant 11%-12% reduction in diabetes risk in people with prediabetes who took vitamin D supplements.

The current secondary analysis of D2d aimed to investigate whether vitamin D supplements affect kidney function in people with prediabetes.

A total of 2,166 participants in D2d with complete kidney function data were included in the analysis.

The three study outcomes were change in estimated glomerular filtration rate (eGFR) from baseline, change in urine albumin-to-creatinine ratio (UACR) from baseline, and worsening Kidney Disease: Improving Global Outcomes (KDIGO) risk score (which takes eGFR and UACR into account).

At baseline, patients were a mean age of 60, had a mean body mass index (BMI) of 32 kg/m², and 44% were women.

Most (79%) had hypertension, 52% were receiving antihypertensives, and 33% were receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB).

Participants had a mean serum 25(OH) level of 28 ng/mL.

They had a mean eGFR of 87 mL/min/1.73 m² and a mean UACR of 11 mg/g. Only 10% had a moderate, high, or very high KDIGO risk score.

Participants were randomized to receive a daily gel pill containing 4,000 IU vitamin D3 (cholecalciferol) or placebo.

Medication adherence was high (83%) in both groups during a median follow-up of 2.9 years.

There was no significant between-group difference in the following kidney function outcomes:

• 28 patients in the vitamin D group and 30 patients in the placebo group had a worsening KDIGO risk score.
• The mean difference in eGFR from baseline was -1.0 mL/min/1.73 m² in the vitamin D group and -0.1 mL/min/1.73 m² in the placebo group.
• The mean difference in UACR from baseline was 2.7 mg/g in the vitamin D group and 2.0 mg/g in the placebo group.  

The authors have reported no relevant financial relationships.

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

Among adults at high risk of type 2 diabetes – the leading cause of kidney disease – those who received vitamin D supplements as opposed to placebo for close to 3 years did not have significant differences in kidney function, in a secondary analysis of the Vitamin D and Type 2 Diabetes (D2d) study.

However, most of these adults with prediabetes plus obesity or overweight also had sufficient serum levels of 25-hydroxyvitamin D (25[OH]D) and a low risk for adverse kidney outcomes at study entry.

“The benefits of vitamin D might be greater in people with low blood vitamin D levels and/or reduced kidney function,” lead author Sun H. Kim, MD, Stanford (Calif.) University, speculated in a statement from the American Society of Nephrology.

The study was published online August 6 in the Clinical Journal of the American Society of Nephrology.

“The D2d study is unique because we recruited individuals with high-risk prediabetes, having two out of three abnormal glucose values, and we recruited more than 2,000 participants, representing the largest vitamin D diabetes prevention trial to date,” Dr. Kim pointed out.

Although the study did not show a benefit of vitamin D supplements on kidney function outcomes, 43% of participants were already taking up to 1,000 IU of vitamin D daily when they entered the study, she noted.

A subgroup analysis of individuals who were not taking vitamin D at study entry found that vitamin D supplements were associated with lowered proteinuria, “which means that it could have a beneficial effect on kidney health,” said Dr. Kim, cautioning that “additional studies are needed to look into this further.”
 

Effect of vitamin D on three kidney function outcomes

Although low levels of serum 25(OH)D are associated with kidney disease, few trials have evaluated how vitamin D supplements might affect kidney function, Dr. Kim and colleagues write.

The D2d trial, they note, found that vitamin D supplements did not lower the risk of incident diabetes in people with prediabetes recruited from medical centers across the United States, as previously reported in 2019.

However, since then, meta-analyses that included the D2d trial have reported a significant 11%-12% reduction in diabetes risk in people with prediabetes who took vitamin D supplements.

The current secondary analysis of D2d aimed to investigate whether vitamin D supplements affect kidney function in people with prediabetes.

A total of 2,166 participants in D2d with complete kidney function data were included in the analysis.

The three study outcomes were change in estimated glomerular filtration rate (eGFR) from baseline, change in urine albumin-to-creatinine ratio (UACR) from baseline, and worsening Kidney Disease: Improving Global Outcomes (KDIGO) risk score (which takes eGFR and UACR into account).

At baseline, patients were a mean age of 60, had a mean body mass index (BMI) of 32 kg/m², and 44% were women.

Most (79%) had hypertension, 52% were receiving antihypertensives, and 33% were receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB).

Participants had a mean serum 25(OH) level of 28 ng/mL.

They had a mean eGFR of 87 mL/min/1.73 m² and a mean UACR of 11 mg/g. Only 10% had a moderate, high, or very high KDIGO risk score.

Participants were randomized to receive a daily gel pill containing 4,000 IU vitamin D3 (cholecalciferol) or placebo.

Medication adherence was high (83%) in both groups during a median follow-up of 2.9 years.

There was no significant between-group difference in the following kidney function outcomes:

• 28 patients in the vitamin D group and 30 patients in the placebo group had a worsening KDIGO risk score.
• The mean difference in eGFR from baseline was -1.0 mL/min/1.73 m² in the vitamin D group and -0.1 mL/min/1.73 m² in the placebo group.
• The mean difference in UACR from baseline was 2.7 mg/g in the vitamin D group and 2.0 mg/g in the placebo group.  

The authors have reported no relevant financial relationships.

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

Among adults at high risk of type 2 diabetes – the leading cause of kidney disease – those who received vitamin D supplements as opposed to placebo for close to 3 years did not have significant differences in kidney function, in a secondary analysis of the Vitamin D and Type 2 Diabetes (D2d) study.

However, most of these adults with prediabetes plus obesity or overweight also had sufficient serum levels of 25-hydroxyvitamin D (25[OH]D) and a low risk for adverse kidney outcomes at study entry.

“The benefits of vitamin D might be greater in people with low blood vitamin D levels and/or reduced kidney function,” lead author Sun H. Kim, MD, Stanford (Calif.) University, speculated in a statement from the American Society of Nephrology.

The study was published online August 6 in the Clinical Journal of the American Society of Nephrology.

“The D2d study is unique because we recruited individuals with high-risk prediabetes, having two out of three abnormal glucose values, and we recruited more than 2,000 participants, representing the largest vitamin D diabetes prevention trial to date,” Dr. Kim pointed out.

Although the study did not show a benefit of vitamin D supplements on kidney function outcomes, 43% of participants were already taking up to 1,000 IU of vitamin D daily when they entered the study, she noted.

A subgroup analysis of individuals who were not taking vitamin D at study entry found that vitamin D supplements were associated with lowered proteinuria, “which means that it could have a beneficial effect on kidney health,” said Dr. Kim, cautioning that “additional studies are needed to look into this further.”
 

Effect of vitamin D on three kidney function outcomes

Although low levels of serum 25(OH)D are associated with kidney disease, few trials have evaluated how vitamin D supplements might affect kidney function, Dr. Kim and colleagues write.

The D2d trial, they note, found that vitamin D supplements did not lower the risk of incident diabetes in people with prediabetes recruited from medical centers across the United States, as previously reported in 2019.

However, since then, meta-analyses that included the D2d trial have reported a significant 11%-12% reduction in diabetes risk in people with prediabetes who took vitamin D supplements.

The current secondary analysis of D2d aimed to investigate whether vitamin D supplements affect kidney function in people with prediabetes.

A total of 2,166 participants in D2d with complete kidney function data were included in the analysis.

The three study outcomes were change in estimated glomerular filtration rate (eGFR) from baseline, change in urine albumin-to-creatinine ratio (UACR) from baseline, and worsening Kidney Disease: Improving Global Outcomes (KDIGO) risk score (which takes eGFR and UACR into account).

At baseline, patients were a mean age of 60, had a mean body mass index (BMI) of 32 kg/m², and 44% were women.

Most (79%) had hypertension, 52% were receiving antihypertensives, and 33% were receiving an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB).

Participants had a mean serum 25(OH) level of 28 ng/mL.

They had a mean eGFR of 87 mL/min/1.73 m² and a mean UACR of 11 mg/g. Only 10% had a moderate, high, or very high KDIGO risk score.

Participants were randomized to receive a daily gel pill containing 4,000 IU vitamin D3 (cholecalciferol) or placebo.

Medication adherence was high (83%) in both groups during a median follow-up of 2.9 years.

There was no significant between-group difference in the following kidney function outcomes:

• 28 patients in the vitamin D group and 30 patients in the placebo group had a worsening KDIGO risk score.
• The mean difference in eGFR from baseline was -1.0 mL/min/1.73 m² in the vitamin D group and -0.1 mL/min/1.73 m² in the placebo group.
• The mean difference in UACR from baseline was 2.7 mg/g in the vitamin D group and 2.0 mg/g in the placebo group.  

The authors have reported no relevant financial relationships.

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

Following the White House administration’s announcement to start booster COVID-19 vaccinations for American adults in September, experts weighed in on the evidence for choosing an 8-month cutoff, how breakthrough infections figure in, and why calling one mRNA vaccine better than the other could be misleading.

Timing came up more than once at the Aug. 18 White House briefing announcing the booster plans. Reporters asked about the start time of Sept. 20 and people waiting at least 8 months after their second mRNA vaccine dose to get a booster.

Anthony Fauci, MD, chief medical adviser to the president and director of the National Institute of Allergy and Infectious Diseases, explained that late September gives the United States time to set up the logistics.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, added that 8 months is in part based on data from Israel and other countries on the waning of vaccine effectiveness over time.

“It is possible that 8 [months] is associated with the amount of time that we’ve been able to follow large groups of people, especially those who are 65 and older,” Julie Swann, PhD, said during a subsequent media briefing sponsored by Newswise on Aug. 18. “I know that Pfizer has said that they think a booster sometime between 6 and 12 months would be reasonable.”

Dr. Swann supported the administration’s booster shots plan. She said it is important “that we continue to get people the full amount of protection if it’s recommended by CDC and ACIP [Advisory Committee on Immunization Practices] that would come from a booster shot.” Dr. Swann is department head and A. Doug Allison Distinguished Professor at North Carolina State University and an adjunct professor in the joint department of biomedical engineering at the University of North Carolina at Chapel Hill. 
 

Rising importance of breakthrough cases

Also on Aug. 18, news emerged that breakthrough cases are on the rise in seven U.S. states, likely because of the Delta variant.

These SARS-CoV-2 infections among the fully vaccinated account for 20% of cases in six of the seven states cited in a New York Times report, for example. Researchers also suggested that hospitalization and deaths associated with breakthrough cases could be higher than previously appreciated.

“It is expected that over time we will see more cases of Delta variant infections among vaccinated people. This points toward the need for booster vaccines and/or eventual modifications to the vaccine to capture new variants in the future,” Juan Wisnivesky, MD, DrPH, chief of the division of general internal medicine at Mount Sinai Health System in New York City, said during the briefing.
 

Vaccine comparisons unfair?

Following the release of a Mayo Clinic study reporting lower effectiveness of the Pfizer mRNA vaccine at 42% versus 76% for the Moderna product, some people started asking if one vaccine was better than the other.

“To begin with, the vaccines are not being compared side-by-side,” Dr. Wisnivesky said. “So we only know the effectiveness of each vaccine versus placebo, but we don’t know one versus the other.”

He added that different study designs, different populations, and other factors make direct comparisons difficult.

More evidence will be needed, Dr. Wisnivesky said, before public health officials can recommend that someone who received one mRNA vaccine switch to another for their booster shot.
 

Layering protections

Continuing to recommend masks is essential, Dr. Swann added. “With this Delta variant, it does appear that the possibility of reinfection or of a disease case breaking through vaccination can occur. So that makes it even more important to consider using nonpharmaceutical interventions while we continue to vaccinate people.”

Wearing or not wearing a mask is one of the behaviors that drive the transmission of disease, Dr. Swann said.

“What we saw across the board is that many people really wanted to go back to normal as much as they could. And we went back to normal a little bit too soon, especially given this new version of the virus that was circulating,” she said.
 

In poll, most favor boosters

A recent poll conducted by Medscape indicates that a majority of vaccinated physicians and nurses are ready and willing to take a COVID-19 booster vaccine. For example, 93% of 943 doctors and 87% of 1,680 nurses who responded want booster shots, either immediately or when they are authorized and recommended.

Among 510 WebMD readers responding to a similar poll, 82% indicated they wanted a booster shot.
 

A challenging task lies ahead

According to CDC data, as of Aug. 18, 2021, almost 169 million Americans are fully vaccinated, including the one-shot Johnson & Johnson adenovirus vaccine.

“I think it will be a challenge to get everyone who is fully vaccinated to come in for that booster,” Dr. Swann said.

Logistically speaking, Dr. Swann explained that many sites that were open for initial vaccinations, including drive-up locations and 24/7 vaccination sites, are no longer operating.

“We might see that rollout look a little bit differently. You might be able to go to your pharmacy or go to your primary care physician,” she said.

“But we may not see as many weekend events so it is going to be easier to get some people a booster than others.

“One interesting thing will also be whether a booster is effective in actually preventing you from giving a disease to someone else,” Dr. Swann said. “That could make a difference as well, because that might play into whether companies, hospitals, universities, or others require a booster.”

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

Following the White House administration’s announcement to start booster COVID-19 vaccinations for American adults in September, experts weighed in on the evidence for choosing an 8-month cutoff, how breakthrough infections figure in, and why calling one mRNA vaccine better than the other could be misleading.

Timing came up more than once at the Aug. 18 White House briefing announcing the booster plans. Reporters asked about the start time of Sept. 20 and people waiting at least 8 months after their second mRNA vaccine dose to get a booster.

Anthony Fauci, MD, chief medical adviser to the president and director of the National Institute of Allergy and Infectious Diseases, explained that late September gives the United States time to set up the logistics.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, added that 8 months is in part based on data from Israel and other countries on the waning of vaccine effectiveness over time.

“It is possible that 8 [months] is associated with the amount of time that we’ve been able to follow large groups of people, especially those who are 65 and older,” Julie Swann, PhD, said during a subsequent media briefing sponsored by Newswise on Aug. 18. “I know that Pfizer has said that they think a booster sometime between 6 and 12 months would be reasonable.”

Dr. Swann supported the administration’s booster shots plan. She said it is important “that we continue to get people the full amount of protection if it’s recommended by CDC and ACIP [Advisory Committee on Immunization Practices] that would come from a booster shot.” Dr. Swann is department head and A. Doug Allison Distinguished Professor at North Carolina State University and an adjunct professor in the joint department of biomedical engineering at the University of North Carolina at Chapel Hill. 
 

Rising importance of breakthrough cases

Also on Aug. 18, news emerged that breakthrough cases are on the rise in seven U.S. states, likely because of the Delta variant.

These SARS-CoV-2 infections among the fully vaccinated account for 20% of cases in six of the seven states cited in a New York Times report, for example. Researchers also suggested that hospitalization and deaths associated with breakthrough cases could be higher than previously appreciated.

“It is expected that over time we will see more cases of Delta variant infections among vaccinated people. This points toward the need for booster vaccines and/or eventual modifications to the vaccine to capture new variants in the future,” Juan Wisnivesky, MD, DrPH, chief of the division of general internal medicine at Mount Sinai Health System in New York City, said during the briefing.
 

Vaccine comparisons unfair?

Following the release of a Mayo Clinic study reporting lower effectiveness of the Pfizer mRNA vaccine at 42% versus 76% for the Moderna product, some people started asking if one vaccine was better than the other.

“To begin with, the vaccines are not being compared side-by-side,” Dr. Wisnivesky said. “So we only know the effectiveness of each vaccine versus placebo, but we don’t know one versus the other.”

He added that different study designs, different populations, and other factors make direct comparisons difficult.

More evidence will be needed, Dr. Wisnivesky said, before public health officials can recommend that someone who received one mRNA vaccine switch to another for their booster shot.
 

Layering protections

Continuing to recommend masks is essential, Dr. Swann added. “With this Delta variant, it does appear that the possibility of reinfection or of a disease case breaking through vaccination can occur. So that makes it even more important to consider using nonpharmaceutical interventions while we continue to vaccinate people.”

Wearing or not wearing a mask is one of the behaviors that drive the transmission of disease, Dr. Swann said.

“What we saw across the board is that many people really wanted to go back to normal as much as they could. And we went back to normal a little bit too soon, especially given this new version of the virus that was circulating,” she said.
 

In poll, most favor boosters

A recent poll conducted by Medscape indicates that a majority of vaccinated physicians and nurses are ready and willing to take a COVID-19 booster vaccine. For example, 93% of 943 doctors and 87% of 1,680 nurses who responded want booster shots, either immediately or when they are authorized and recommended.

Among 510 WebMD readers responding to a similar poll, 82% indicated they wanted a booster shot.
 

A challenging task lies ahead

According to CDC data, as of Aug. 18, 2021, almost 169 million Americans are fully vaccinated, including the one-shot Johnson & Johnson adenovirus vaccine.

“I think it will be a challenge to get everyone who is fully vaccinated to come in for that booster,” Dr. Swann said.

Logistically speaking, Dr. Swann explained that many sites that were open for initial vaccinations, including drive-up locations and 24/7 vaccination sites, are no longer operating.

“We might see that rollout look a little bit differently. You might be able to go to your pharmacy or go to your primary care physician,” she said.

“But we may not see as many weekend events so it is going to be easier to get some people a booster than others.

“One interesting thing will also be whether a booster is effective in actually preventing you from giving a disease to someone else,” Dr. Swann said. “That could make a difference as well, because that might play into whether companies, hospitals, universities, or others require a booster.”

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

Following the White House administration’s announcement to start booster COVID-19 vaccinations for American adults in September, experts weighed in on the evidence for choosing an 8-month cutoff, how breakthrough infections figure in, and why calling one mRNA vaccine better than the other could be misleading.

Timing came up more than once at the Aug. 18 White House briefing announcing the booster plans. Reporters asked about the start time of Sept. 20 and people waiting at least 8 months after their second mRNA vaccine dose to get a booster.

Anthony Fauci, MD, chief medical adviser to the president and director of the National Institute of Allergy and Infectious Diseases, explained that late September gives the United States time to set up the logistics.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, added that 8 months is in part based on data from Israel and other countries on the waning of vaccine effectiveness over time.

“It is possible that 8 [months] is associated with the amount of time that we’ve been able to follow large groups of people, especially those who are 65 and older,” Julie Swann, PhD, said during a subsequent media briefing sponsored by Newswise on Aug. 18. “I know that Pfizer has said that they think a booster sometime between 6 and 12 months would be reasonable.”

Dr. Swann supported the administration’s booster shots plan. She said it is important “that we continue to get people the full amount of protection if it’s recommended by CDC and ACIP [Advisory Committee on Immunization Practices] that would come from a booster shot.” Dr. Swann is department head and A. Doug Allison Distinguished Professor at North Carolina State University and an adjunct professor in the joint department of biomedical engineering at the University of North Carolina at Chapel Hill. 
 

Rising importance of breakthrough cases

Also on Aug. 18, news emerged that breakthrough cases are on the rise in seven U.S. states, likely because of the Delta variant.

These SARS-CoV-2 infections among the fully vaccinated account for 20% of cases in six of the seven states cited in a New York Times report, for example. Researchers also suggested that hospitalization and deaths associated with breakthrough cases could be higher than previously appreciated.

“It is expected that over time we will see more cases of Delta variant infections among vaccinated people. This points toward the need for booster vaccines and/or eventual modifications to the vaccine to capture new variants in the future,” Juan Wisnivesky, MD, DrPH, chief of the division of general internal medicine at Mount Sinai Health System in New York City, said during the briefing.
 

Vaccine comparisons unfair?

Following the release of a Mayo Clinic study reporting lower effectiveness of the Pfizer mRNA vaccine at 42% versus 76% for the Moderna product, some people started asking if one vaccine was better than the other.

“To begin with, the vaccines are not being compared side-by-side,” Dr. Wisnivesky said. “So we only know the effectiveness of each vaccine versus placebo, but we don’t know one versus the other.”

He added that different study designs, different populations, and other factors make direct comparisons difficult.

More evidence will be needed, Dr. Wisnivesky said, before public health officials can recommend that someone who received one mRNA vaccine switch to another for their booster shot.
 

Layering protections

Continuing to recommend masks is essential, Dr. Swann added. “With this Delta variant, it does appear that the possibility of reinfection or of a disease case breaking through vaccination can occur. So that makes it even more important to consider using nonpharmaceutical interventions while we continue to vaccinate people.”

Wearing or not wearing a mask is one of the behaviors that drive the transmission of disease, Dr. Swann said.

“What we saw across the board is that many people really wanted to go back to normal as much as they could. And we went back to normal a little bit too soon, especially given this new version of the virus that was circulating,” she said.
 

In poll, most favor boosters

A recent poll conducted by Medscape indicates that a majority of vaccinated physicians and nurses are ready and willing to take a COVID-19 booster vaccine. For example, 93% of 943 doctors and 87% of 1,680 nurses who responded want booster shots, either immediately or when they are authorized and recommended.

Among 510 WebMD readers responding to a similar poll, 82% indicated they wanted a booster shot.
 

A challenging task lies ahead

According to CDC data, as of Aug. 18, 2021, almost 169 million Americans are fully vaccinated, including the one-shot Johnson & Johnson adenovirus vaccine.

“I think it will be a challenge to get everyone who is fully vaccinated to come in for that booster,” Dr. Swann said.

Logistically speaking, Dr. Swann explained that many sites that were open for initial vaccinations, including drive-up locations and 24/7 vaccination sites, are no longer operating.

“We might see that rollout look a little bit differently. You might be able to go to your pharmacy or go to your primary care physician,” she said.

“But we may not see as many weekend events so it is going to be easier to get some people a booster than others.

“One interesting thing will also be whether a booster is effective in actually preventing you from giving a disease to someone else,” Dr. Swann said. “That could make a difference as well, because that might play into whether companies, hospitals, universities, or others require a booster.”

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

Editor’s note: In this article, we present an archetypal ethics challenge in hospital medicine. The authors, members of the SHM’s Ethics Special Interest Group and clinical ethics consultants at their respective hospitals, will comment on the questions and practical approaches for hospitalists.

Ms. S, an 82-year-old woman with severe dementia, was initially hospitalized in the ICU with acute on chronic respiratory failure. Prior to admission, Ms. S lived with her daughter, who is her primary caregiver. Ms. S is able to say her daughter’s name, and answer “yes” and “no” to simple questions. She is bed bound, incontinent of urine and feces, and dependent on her daughter for all ADLs.

This admission, Ms. S has been re-intubated 4 times for recurrent respiratory failure. The nursing staff are distressed that she is suffering physically. Her daughter requests to continue all intensive, life-prolonging treatment including mechanical ventilation and artificial nutrition.

During sign out, your colleague remarks that his grandmother was in a similar situation and that his family chose to pursue comfort care. He questions whether Ms. S has any quality of life and asks if you think further intensive care is futile.

On your first day caring for Ms. S, you contact her primary care provider. Her PCP reports that Ms. S and her daughter completed an advance directive (AD) 10 years ago which documents a preference for all life prolonging treatment.
 

Question #1: What are the ethical challenges?

Dr. Chase: In caring for Ms. S, we face a common ethical challenge: how to respect the patient’s prior preferences (autonomy) when the currently requested treatments have diminishing benefits (beneficence) and escalating harms (non-maleficence). Life-prolonging care can have diminishing returns at the end of life. Ms. S’s loss of decision-making capacity adds a layer of complexity. Her AD was completed when she was able to consider decisions about her care, and she might make different decisions in her current state of health. Shared decision-making with a surrogate can be complicated by a surrogate’s anxiety with making life-altering decisions or their desire to avoid guilt or loneliness. Health care professionals face the limits of scientific knowledge in delivering accurate prognostic estimates, probabilities of recovery, and likelihood of benefit from interventions. In addition to the guideposts of ethical principles, some hospitals have policies which advise clinicians to avoid non-beneficial care.

Such situations are emotionally intense and can trigger distress among patients, families, caregivers and health care professionals. Conscious and unconscious bias about a patient’s perceived quality of life undermines equity and can play a role in our recommendations for patients of advanced age, with cognitive impairment, and those who live with a disability.
 

Question #2: How might you meet the patient’s medical needs in line with her goals?

Dr. Khawaja: In order to provide care consistent with the patient’s goals, the first step is to clarify these goals with Ms. S’s surrogate decision-maker, her daughter. In a previously autonomous but presently incapacitated patient, the previously expressed preferences in the form of a written AD should be respected. However, the AD is only a set of preferences completed at a particular time, not medical orders. The clinician and surrogate must consider how to apply the AD to the current clinical circumstances. The clinician should verify that the clinical circumstances specified in the AD have been met and evaluate if the patient’s preferences have changed since she originally completed the AD.

Surrogates are asked to use a Substituted Judgement Standard (i.e., what would the patient choose in this situation if known). This may differ from what the surrogate wants. If not known, surrogates are asked to use the Best Interest Standard (i.e., what would bring the most net benefit to the patient by weighing benefits and risks of treatment options). I often ask the surrogate, “Tell us about your loved one.” Or, “Knowing your loved one, what do you think would be the most important for her right now?”¹

I would also caution against bias in judging quality of life in patients with dementia, and using the term “futility,” as these concepts are inherently subjective. In general, when a colleague raises the issue of futility, I begin by asking, “…futile to achieve what goal?” That can help clarify some of the disagreement as some goals can be accomplished while others cannot.

Finally, I work to include other members of our team in these discussions. The distress of nurses, social workers, and others are important to acknowledge, validate, and involve in the problem-solving process.
 

Question #3: If you were Ms. S’s hospitalist, what would you do?

Dr. Khawaja: As the hospitalist caring for Ms. S, I would use the “four boxes” model as a helpful, clinically relevant and systematic approach to managing ethical concerns.²

This “four boxes” model gives us a practical framework to address these ethical principles by asking questions in four domains.

Medical indications: What is the nature of her current illness, and is it reversible or not? What is the probability of success of treatment options like mechanical ventilation? Are there adverse effects of treatment?

Patient preferences: Since Ms. S lacks capacity, does her daughter understand the benefits and burdens of treatment? What are the goals of treatment? Prolonging life? Minimizing discomfort? Spending time with loved ones? What burdens would the patient be willing to endure to reach her goals?

Quality of life: What would the patient’s quality of life be with and without the treatments?

Contextual features: My priorities would be building a relationship of trust with Ms. S’s daughter – by educating her about her mother’s clinical status, addressing her concerns and questions, and supporting her as we work through patient-centered decisions about what is best for her mother. Honest communication is a must, even if it means acknowledging uncertainties about the course of disease and prognosis.

These are not easy decisions for surrogates to make. They should be given time to process information and to make what they believe are the best decisions for their loved ones. It is critical for clinicians to provide honest and complete clinical information and to avoid value judgments, bias, or unreasonable time pressure. While one-on-one conversations are central, I find that multidisciplinary meetings allow all stakeholders to ask and answer vital questions and ideally to reach consensus in treatment planning.

Dr. Chase: In caring for Ms. S, I would use a structured approach to discussions with her daughter, such as the “SPIKES” protocol.³ Using open ended questions, I would ask about the patient’s and her daughter’s goals, values, and fears and provide support about the responsibility for shared-decision making and the difficulty of uncertainty. Reflecting statements can help in confirming understanding and showing attention (e.g. “I hear that avoiding discomfort would be important to your mother.”)

I find it helpful to emphasize my commitment to honesty and non-abandonment (a common fear among patients and families). By offering to provide recommendations about both disease-directed and palliative, comfort-focused interventions, the patient’s daughter has an opportunity to engage voluntarily in discussion. When asked about care that may have marginal benefit, I suggest time-limited trials.⁴ I do not offer non-beneficial treatments and if asked about such treatments, I note the underlying motive and why the treatment is not feasible (“I see that you are hoping that your mother will live longer, but I am concerned that tube feeding will not help because…”), offer preferable alternatives, and leave space for questions and emotions. It is important not to force a premature resolution of the situation through unilateral or coercive decisions⁵ (i.e., going off service does not mean I have to wrap up the existential crisis which is occurring.) A broader challenge is the grief and other emotions which accompany illness and death. I can neither prevent death nor grief, but I can offer my professional guidance and provide a supportive space for the patient and family to experience this transition. By acknowledging this, I center myself with the patient and family and we can work together toward a common goal of providing compassionate and ethical care.

Dr. Chase is associate professor, Department of Family and Community Medicine, University of California San Francisco; and co-chair, Ethics Committee, San Francisco General Hospital. Dr. Khawaja is assistant professor, Department of Internal Medicine, Baylor College of Medicine, Houston, and a member of the Ethics Committee of the Society of General Internal Medicine.

References

1. Sulmasy DP, Snyder L. Substituted interests and best judgments: an integrated model of surrogate decision making. JAMA. 2010 Nov 3;304(17):1946-7. doi: 10.1001/jama.2010.159.

2. Jonsen AR, Siegler M, Winslade WJ. Clinical ethics: A practical approach to ethical decisions in clinical medicine. 6th ed. New York: McGraw Hill Medical; 2006.

3. Baile WF, et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4):302–311. doi: 10.1634/theoncologist.5-4-302.

4. Chang DW, et al. Evaluation of time-limited trials among critically ill patients with advanced medical illnesses and reduction of nonbeneficial ICU treatments. JAMA Intern Med. 2021;181(6):786–794. doi: 10.1001/jamainternmed.2021.1000.

5. Sedig, L. What’s the role of autonomy in patient-and family-centered care when patients and family members don’t agree? AMA J Ethics. 2016;18(1):12-17. doi: 10.1001/journalofethics.2017.18.1.ecas2-1601.

Editor’s note: In this article, we present an archetypal ethics challenge in hospital medicine. The authors, members of the SHM’s Ethics Special Interest Group and clinical ethics consultants at their respective hospitals, will comment on the questions and practical approaches for hospitalists.

Ms. S, an 82-year-old woman with severe dementia, was initially hospitalized in the ICU with acute on chronic respiratory failure. Prior to admission, Ms. S lived with her daughter, who is her primary caregiver. Ms. S is able to say her daughter’s name, and answer “yes” and “no” to simple questions. She is bed bound, incontinent of urine and feces, and dependent on her daughter for all ADLs.

This admission, Ms. S has been re-intubated 4 times for recurrent respiratory failure. The nursing staff are distressed that she is suffering physically. Her daughter requests to continue all intensive, life-prolonging treatment including mechanical ventilation and artificial nutrition.

During sign out, your colleague remarks that his grandmother was in a similar situation and that his family chose to pursue comfort care. He questions whether Ms. S has any quality of life and asks if you think further intensive care is futile.

On your first day caring for Ms. S, you contact her primary care provider. Her PCP reports that Ms. S and her daughter completed an advance directive (AD) 10 years ago which documents a preference for all life prolonging treatment.
 

Question #1: What are the ethical challenges?

Dr. Chase: In caring for Ms. S, we face a common ethical challenge: how to respect the patient’s prior preferences (autonomy) when the currently requested treatments have diminishing benefits (beneficence) and escalating harms (non-maleficence). Life-prolonging care can have diminishing returns at the end of life. Ms. S’s loss of decision-making capacity adds a layer of complexity. Her AD was completed when she was able to consider decisions about her care, and she might make different decisions in her current state of health. Shared decision-making with a surrogate can be complicated by a surrogate’s anxiety with making life-altering decisions or their desire to avoid guilt or loneliness. Health care professionals face the limits of scientific knowledge in delivering accurate prognostic estimates, probabilities of recovery, and likelihood of benefit from interventions. In addition to the guideposts of ethical principles, some hospitals have policies which advise clinicians to avoid non-beneficial care.

Such situations are emotionally intense and can trigger distress among patients, families, caregivers and health care professionals. Conscious and unconscious bias about a patient’s perceived quality of life undermines equity and can play a role in our recommendations for patients of advanced age, with cognitive impairment, and those who live with a disability.
 

Question #2: How might you meet the patient’s medical needs in line with her goals?

Dr. Khawaja: In order to provide care consistent with the patient’s goals, the first step is to clarify these goals with Ms. S’s surrogate decision-maker, her daughter. In a previously autonomous but presently incapacitated patient, the previously expressed preferences in the form of a written AD should be respected. However, the AD is only a set of preferences completed at a particular time, not medical orders. The clinician and surrogate must consider how to apply the AD to the current clinical circumstances. The clinician should verify that the clinical circumstances specified in the AD have been met and evaluate if the patient’s preferences have changed since she originally completed the AD.

Surrogates are asked to use a Substituted Judgement Standard (i.e., what would the patient choose in this situation if known). This may differ from what the surrogate wants. If not known, surrogates are asked to use the Best Interest Standard (i.e., what would bring the most net benefit to the patient by weighing benefits and risks of treatment options). I often ask the surrogate, “Tell us about your loved one.” Or, “Knowing your loved one, what do you think would be the most important for her right now?”¹

I would also caution against bias in judging quality of life in patients with dementia, and using the term “futility,” as these concepts are inherently subjective. In general, when a colleague raises the issue of futility, I begin by asking, “…futile to achieve what goal?” That can help clarify some of the disagreement as some goals can be accomplished while others cannot.

Finally, I work to include other members of our team in these discussions. The distress of nurses, social workers, and others are important to acknowledge, validate, and involve in the problem-solving process.
 

Question #3: If you were Ms. S’s hospitalist, what would you do?

Dr. Khawaja: As the hospitalist caring for Ms. S, I would use the “four boxes” model as a helpful, clinically relevant and systematic approach to managing ethical concerns.²

This “four boxes” model gives us a practical framework to address these ethical principles by asking questions in four domains.

Medical indications: What is the nature of her current illness, and is it reversible or not? What is the probability of success of treatment options like mechanical ventilation? Are there adverse effects of treatment?

Patient preferences: Since Ms. S lacks capacity, does her daughter understand the benefits and burdens of treatment? What are the goals of treatment? Prolonging life? Minimizing discomfort? Spending time with loved ones? What burdens would the patient be willing to endure to reach her goals?

Quality of life: What would the patient’s quality of life be with and without the treatments?

Contextual features: My priorities would be building a relationship of trust with Ms. S’s daughter – by educating her about her mother’s clinical status, addressing her concerns and questions, and supporting her as we work through patient-centered decisions about what is best for her mother. Honest communication is a must, even if it means acknowledging uncertainties about the course of disease and prognosis.

These are not easy decisions for surrogates to make. They should be given time to process information and to make what they believe are the best decisions for their loved ones. It is critical for clinicians to provide honest and complete clinical information and to avoid value judgments, bias, or unreasonable time pressure. While one-on-one conversations are central, I find that multidisciplinary meetings allow all stakeholders to ask and answer vital questions and ideally to reach consensus in treatment planning.

Dr. Chase: In caring for Ms. S, I would use a structured approach to discussions with her daughter, such as the “SPIKES” protocol.³ Using open ended questions, I would ask about the patient’s and her daughter’s goals, values, and fears and provide support about the responsibility for shared-decision making and the difficulty of uncertainty. Reflecting statements can help in confirming understanding and showing attention (e.g. “I hear that avoiding discomfort would be important to your mother.”)

I find it helpful to emphasize my commitment to honesty and non-abandonment (a common fear among patients and families). By offering to provide recommendations about both disease-directed and palliative, comfort-focused interventions, the patient’s daughter has an opportunity to engage voluntarily in discussion. When asked about care that may have marginal benefit, I suggest time-limited trials.⁴ I do not offer non-beneficial treatments and if asked about such treatments, I note the underlying motive and why the treatment is not feasible (“I see that you are hoping that your mother will live longer, but I am concerned that tube feeding will not help because…”), offer preferable alternatives, and leave space for questions and emotions. It is important not to force a premature resolution of the situation through unilateral or coercive decisions⁵ (i.e., going off service does not mean I have to wrap up the existential crisis which is occurring.) A broader challenge is the grief and other emotions which accompany illness and death. I can neither prevent death nor grief, but I can offer my professional guidance and provide a supportive space for the patient and family to experience this transition. By acknowledging this, I center myself with the patient and family and we can work together toward a common goal of providing compassionate and ethical care.

Dr. Chase is associate professor, Department of Family and Community Medicine, University of California San Francisco; and co-chair, Ethics Committee, San Francisco General Hospital. Dr. Khawaja is assistant professor, Department of Internal Medicine, Baylor College of Medicine, Houston, and a member of the Ethics Committee of the Society of General Internal Medicine.

References

1. Sulmasy DP, Snyder L. Substituted interests and best judgments: an integrated model of surrogate decision making. JAMA. 2010 Nov 3;304(17):1946-7. doi: 10.1001/jama.2010.159.

2. Jonsen AR, Siegler M, Winslade WJ. Clinical ethics: A practical approach to ethical decisions in clinical medicine. 6th ed. New York: McGraw Hill Medical; 2006.

3. Baile WF, et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4):302–311. doi: 10.1634/theoncologist.5-4-302.

4. Chang DW, et al. Evaluation of time-limited trials among critically ill patients with advanced medical illnesses and reduction of nonbeneficial ICU treatments. JAMA Intern Med. 2021;181(6):786–794. doi: 10.1001/jamainternmed.2021.1000.

5. Sedig, L. What’s the role of autonomy in patient-and family-centered care when patients and family members don’t agree? AMA J Ethics. 2016;18(1):12-17. doi: 10.1001/journalofethics.2017.18.1.ecas2-1601.

Editor’s note: In this article, we present an archetypal ethics challenge in hospital medicine. The authors, members of the SHM’s Ethics Special Interest Group and clinical ethics consultants at their respective hospitals, will comment on the questions and practical approaches for hospitalists.

Ms. S, an 82-year-old woman with severe dementia, was initially hospitalized in the ICU with acute on chronic respiratory failure. Prior to admission, Ms. S lived with her daughter, who is her primary caregiver. Ms. S is able to say her daughter’s name, and answer “yes” and “no” to simple questions. She is bed bound, incontinent of urine and feces, and dependent on her daughter for all ADLs.

This admission, Ms. S has been re-intubated 4 times for recurrent respiratory failure. The nursing staff are distressed that she is suffering physically. Her daughter requests to continue all intensive, life-prolonging treatment including mechanical ventilation and artificial nutrition.

During sign out, your colleague remarks that his grandmother was in a similar situation and that his family chose to pursue comfort care. He questions whether Ms. S has any quality of life and asks if you think further intensive care is futile.

On your first day caring for Ms. S, you contact her primary care provider. Her PCP reports that Ms. S and her daughter completed an advance directive (AD) 10 years ago which documents a preference for all life prolonging treatment.
 

Question #1: What are the ethical challenges?

Dr. Chase: In caring for Ms. S, we face a common ethical challenge: how to respect the patient’s prior preferences (autonomy) when the currently requested treatments have diminishing benefits (beneficence) and escalating harms (non-maleficence). Life-prolonging care can have diminishing returns at the end of life. Ms. S’s loss of decision-making capacity adds a layer of complexity. Her AD was completed when she was able to consider decisions about her care, and she might make different decisions in her current state of health. Shared decision-making with a surrogate can be complicated by a surrogate’s anxiety with making life-altering decisions or their desire to avoid guilt or loneliness. Health care professionals face the limits of scientific knowledge in delivering accurate prognostic estimates, probabilities of recovery, and likelihood of benefit from interventions. In addition to the guideposts of ethical principles, some hospitals have policies which advise clinicians to avoid non-beneficial care.

Such situations are emotionally intense and can trigger distress among patients, families, caregivers and health care professionals. Conscious and unconscious bias about a patient’s perceived quality of life undermines equity and can play a role in our recommendations for patients of advanced age, with cognitive impairment, and those who live with a disability.
 

Question #2: How might you meet the patient’s medical needs in line with her goals?

Dr. Khawaja: In order to provide care consistent with the patient’s goals, the first step is to clarify these goals with Ms. S’s surrogate decision-maker, her daughter. In a previously autonomous but presently incapacitated patient, the previously expressed preferences in the form of a written AD should be respected. However, the AD is only a set of preferences completed at a particular time, not medical orders. The clinician and surrogate must consider how to apply the AD to the current clinical circumstances. The clinician should verify that the clinical circumstances specified in the AD have been met and evaluate if the patient’s preferences have changed since she originally completed the AD.

Surrogates are asked to use a Substituted Judgement Standard (i.e., what would the patient choose in this situation if known). This may differ from what the surrogate wants. If not known, surrogates are asked to use the Best Interest Standard (i.e., what would bring the most net benefit to the patient by weighing benefits and risks of treatment options). I often ask the surrogate, “Tell us about your loved one.” Or, “Knowing your loved one, what do you think would be the most important for her right now?”¹

I would also caution against bias in judging quality of life in patients with dementia, and using the term “futility,” as these concepts are inherently subjective. In general, when a colleague raises the issue of futility, I begin by asking, “…futile to achieve what goal?” That can help clarify some of the disagreement as some goals can be accomplished while others cannot.

Finally, I work to include other members of our team in these discussions. The distress of nurses, social workers, and others are important to acknowledge, validate, and involve in the problem-solving process.
 

Question #3: If you were Ms. S’s hospitalist, what would you do?

Dr. Khawaja: As the hospitalist caring for Ms. S, I would use the “four boxes” model as a helpful, clinically relevant and systematic approach to managing ethical concerns.²

This “four boxes” model gives us a practical framework to address these ethical principles by asking questions in four domains.

Medical indications: What is the nature of her current illness, and is it reversible or not? What is the probability of success of treatment options like mechanical ventilation? Are there adverse effects of treatment?

Patient preferences: Since Ms. S lacks capacity, does her daughter understand the benefits and burdens of treatment? What are the goals of treatment? Prolonging life? Minimizing discomfort? Spending time with loved ones? What burdens would the patient be willing to endure to reach her goals?

Quality of life: What would the patient’s quality of life be with and without the treatments?

Contextual features: My priorities would be building a relationship of trust with Ms. S’s daughter – by educating her about her mother’s clinical status, addressing her concerns and questions, and supporting her as we work through patient-centered decisions about what is best for her mother. Honest communication is a must, even if it means acknowledging uncertainties about the course of disease and prognosis.

These are not easy decisions for surrogates to make. They should be given time to process information and to make what they believe are the best decisions for their loved ones. It is critical for clinicians to provide honest and complete clinical information and to avoid value judgments, bias, or unreasonable time pressure. While one-on-one conversations are central, I find that multidisciplinary meetings allow all stakeholders to ask and answer vital questions and ideally to reach consensus in treatment planning.

Dr. Chase: In caring for Ms. S, I would use a structured approach to discussions with her daughter, such as the “SPIKES” protocol.³ Using open ended questions, I would ask about the patient’s and her daughter’s goals, values, and fears and provide support about the responsibility for shared-decision making and the difficulty of uncertainty. Reflecting statements can help in confirming understanding and showing attention (e.g. “I hear that avoiding discomfort would be important to your mother.”)

I find it helpful to emphasize my commitment to honesty and non-abandonment (a common fear among patients and families). By offering to provide recommendations about both disease-directed and palliative, comfort-focused interventions, the patient’s daughter has an opportunity to engage voluntarily in discussion. When asked about care that may have marginal benefit, I suggest time-limited trials.⁴ I do not offer non-beneficial treatments and if asked about such treatments, I note the underlying motive and why the treatment is not feasible (“I see that you are hoping that your mother will live longer, but I am concerned that tube feeding will not help because…”), offer preferable alternatives, and leave space for questions and emotions. It is important not to force a premature resolution of the situation through unilateral or coercive decisions⁵ (i.e., going off service does not mean I have to wrap up the existential crisis which is occurring.) A broader challenge is the grief and other emotions which accompany illness and death. I can neither prevent death nor grief, but I can offer my professional guidance and provide a supportive space for the patient and family to experience this transition. By acknowledging this, I center myself with the patient and family and we can work together toward a common goal of providing compassionate and ethical care.

Dr. Chase is associate professor, Department of Family and Community Medicine, University of California San Francisco; and co-chair, Ethics Committee, San Francisco General Hospital. Dr. Khawaja is assistant professor, Department of Internal Medicine, Baylor College of Medicine, Houston, and a member of the Ethics Committee of the Society of General Internal Medicine.

References

1. Sulmasy DP, Snyder L. Substituted interests and best judgments: an integrated model of surrogate decision making. JAMA. 2010 Nov 3;304(17):1946-7. doi: 10.1001/jama.2010.159.

2. Jonsen AR, Siegler M, Winslade WJ. Clinical ethics: A practical approach to ethical decisions in clinical medicine. 6th ed. New York: McGraw Hill Medical; 2006.

3. Baile WF, et al. SPIKES-A six-step protocol for delivering bad news: application to the patient with cancer. Oncologist. 2000;5(4):302–311. doi: 10.1634/theoncologist.5-4-302.

4. Chang DW, et al. Evaluation of time-limited trials among critically ill patients with advanced medical illnesses and reduction of nonbeneficial ICU treatments. JAMA Intern Med. 2021;181(6):786–794. doi: 10.1001/jamainternmed.2021.1000.

5. Sedig, L. What’s the role of autonomy in patient-and family-centered care when patients and family members don’t agree? AMA J Ethics. 2016;18(1):12-17. doi: 10.1001/journalofethics.2017.18.1.ecas2-1601.