Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

Systemic mastocytosis is widely underdiagnosed, and many more hematologic oncologists should be looking for it. This call to action was issued late in 2022 by Stanford (Calif.) Cancer Institute’s Jason Gotlib, MD, speaking at the Lymphoma, Leukemia & Myeloma Congress in New York.

Nationwide, approximately 1,000 adults are diagnosed with systemic mastocytosis annually. This rare disease is a myeloid neoplasm with a highly variable phenotypic expression, in which abnormal mast cells proliferate and infiltrate organs and tissues. It swings widely from a nonadvanced form, composed of indolent or smoldering disease, to advanced disease that progresses to leukemia in 6% of cases.

More than 80% of systemic mastocytosis is driven by the KIT D816V mutation. Along with a host of other rare KIT mutations, KIT D816V activates KIT-receptor tyrosine kinase to trigger mast cell proliferation.

Dr. Gotlib could not be contacted for an interview. However, there are many good reasons to identify patients with systemic mastocytosis, according to Attilio Orazi, MD, professor and chair of the department of pathology at Texas Tech University, El Paso. The chief reason is that the patient may be in grave peril.

“The degree of heterogeneity is amazing. ... There’s very indolent [disease], which is really not a big deal. And then you have a disease in which you’re dead in 3 months,” Dr. Orazi said. “So you run the gamut between an indolent, no-problem cutaneous disease to a very nasty systemic, aggressive leukemia-like neoplasm.”

Since 2001, the diagnosis of mastocytosis has been guided by the World Health Organization Classification of Tumours, or “Blue Book.” In 2022, Dr. Orazi along with 137 other senior experts, most of whom were involved in past editions of the Blue Book, published their own version: The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (the ICC 2022).

In September 2021, this group of specialists held a virtual/in-person advisory committee meeting at the University of Chicago to create the document. One factor in their decision to go it alone, Dr. Orazi said, was that WHO decided to proceed with the fifth edition of the Blue Book using its own internal editorial group without convening an advisory committee, despite repeated requests to do so.

ICC 2022 divides advanced systemic mastocytosis into three subtypes: aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL). Median survival is 3.5 years for patients with ASM, 2 years for those with SM-AHN and as low as 2 months for MCL.

The second key reason to increase awareness of mastocytosis among physicians, said Dr. Orazi, is that patients falling through the net are likely to be ambulatory, and their presentation can be “a little confusing.”

Patients with indolent disease are relatively straightforward to recognize, explained Dr. Orazi. Similarly, very sick patients with SM-AHN or MCL are easily recognized by hem-oncs.

“But if you see a patient in an ambulatory setting, in your clinic or whatever, and you’re suspicious, then you need to decide [how] you’re going to investigate that patient further,” he said, Dr. Orazi noted the next step is not always obvious, especially for primary-practice or internal medicine physicians likely to be unfamiliar with such a rare disease.

A practice survey published in 2022 by other researchers backed up Dr. Orazi’s remarks. The study found that community/solo-practice physicians were less likely to have tested systemic mastocytosis patients for KIT816V mutation than academic/specialty physicians (58% vs. 80%; P = .004; n = 111). Clinicians treating these patients estimated that it took an average of 8.5 months for a “typical” patient to receive the diagnosis from the time of symptom onset.

The research was headed by Ruben Mesa, MD, director of University of Texas Health, San Antonio, and funded by Blueprint Medicines, the manufacturer of avapritinib (Ayvakit), a new drug for the disease.

Dr. Orazi urged clinicians to have a high degree of suspicion for mastocytosis in a patient who walks into the clinic with any combination of the following: urticarial-type skin manifestations, especially if persistent into adulthood; history of undue reaction to an insect sting; a big spleen in a patient with a history of cutaneous flushing or rash; chronic diarrhea, especially if a biopsy has shown “too many mast cells” in the lamina propria of the small bowel; and positivity for KIT816V mutation.

Dr. Orazi stressed that the majority of patients will have indolent disease, but for the few patients for whom immediate treatment is essential, “the distinction between indolent and aggressive [disease] is really very, very important.”

Patients with advanced systemic mastocytosis can now be effectively treated, following the arrival of midostaurin (Rydapt, Tauritmo) and avapritinib.

Midostaurin, a multikinase/KIT inhibitor, was approved by the Food and Drug Administration in 2017 for the treatment of advanced systemic mastocytosis (ASM, SM-AHN, and MCL). Avapritinib, a selective kinase inhibitor of KIT816V and platelet-derived growth factor receptor alpha as well as multiple KIT exon 11, 11/17 and 17 mutants, gained the same indication in June 2021.

As with all rare diseases, it is challenging to obtain accurate numbers on how many patients are affected by systemic mastocytosis. The first population-based study of the disorder, presented at the 2018 annual meeting of the American Society of Hematology, used the Surveillance, Epidemiology, and End Results database from 2000 to 2014 to estimate incidence at 0.046 per 10,000, which translates to 1,050 new adult cases per year. The study data have never been published in full.

How many of these cases are advanced disease? There are no U.S. data but extrapolating from a Danish registry study that found 82% of systemic mastocytosis cases to be indolent disease, the incidence of advanced systemic mastocytosis in the United States could be as low as 200 adults a year.

This information, in turn, suggests that identifying more patients with advanced disease would not only benefit those patients but would also benefit clinical trial investigators who are seeking the proverbial needle in the haystack.

Nationwide, five clinical trials are recruiting individuals with advanced systemic mastocytosis, collectively looking for 352 patients in the United States. Two of the studies focus on mast-cell activation (NCT0544944) and cutaneous mastocytoses (NCT04846348). Two trials in a range of hematological malignancies are testing bispecific antibodies flotetuzumab and MGD024 (both from Macrogenics; NCT04681105, NCT05362773).

Apex, a phase 2 study of tyrosine-kinase inhibitor bezuclastinib (a Cogent hopeful), is specifically focusing on advanced disease. Dr. Gotlib and coinvestigators are aiming for 140 participants.

As a pathologist, Dr. Orazi said he find mastocytosis fascinating because he believes he has “a truly useful role,” contrasting with some other hematological diseases in which the molecular profile rules.

“Pathology plays a major role here,” he explained, “because you have to correlate what you see at the microscope with the full clinical picture, selected laboratory tests such as CBC and serum tryptase, and molecular results. You often need integration through a pathologist to put all the pieces together.

“It’s easier to treat once you know exactly what disease you’re dealing with and whether it is an aggressive or indolent subtype,” Dr. Orazi concluded.

Dr. Orazi disclosed no conflicts of interest. Dr. Gotlib has disclosed ties with Blueprint Medicines, Deciphera, Incyte, and Kartos Therapeutics, and has led committees for Blueprint Medicine’s EXPLORER and PATHFINDER studies, Deciphera’s Study Steering Committee for ripretinib in AdvSM, and the Central Response Review Committee for the phase 2 study of bezuclastinib in AdvSM.

PCSK9 inhibitors may best be known for their powerful LDL-lowering effects but are less appreciated as anti-inflammatory agents with potential beyond cardiovascular health.

In a small pilot trial, for example, patients hospitalized with severe COVID-19 who received a single injection of PCSK9 inhibitor became less sick and more likely to survive than those given a placebo. Their 30-day risk of death or intubation fell significantly, as did their levels of the inflammatory cytokine interleukin 6 (IL-6).

Indeed, survival gains in the PCSK9-inhibitor group were greatest among patients with higher baseline concentrations of IL-6. Although the trial wasn’t powered for clinical outcomes, it suggests the drugs’ efficacy in COVID-19 tracks with intensity of inflammation, proposes a report published  in the Journal of the American College of Cardiology.

Therefore, “PCSK9 inhibition may represent a novel therapeutic pathway in addition to currently recommended therapeutic approaches for severe COVID-19,” conclude the authors, led by Eliano P. Navarese, MD, PhD, Nicolaus Copernicus University, Bydgoszcz, Poland.
 

PCSK9 inhibitors as anti-inflammatories

Although the study was small and only hypothesis-generating, the fact that outcomes for actively treated patients were proportional to baseline IL-6 levels “strongly suggests that PCSK9 inhibition can directly modulate inflammation in COVID-19,” argues an editorial accompanying the report.

The study adds to “our clinical arsenal against COVID-19,” and likely sheds light on “mechanisms through which PCSK9 inhibition dually modulates lipoprotein metabolism and inflammation,” write Sascha N. Goonewardena, MD, University of Michigan, Ann Arbor, and Robert S. Rosenson, MD, Icahn School of Medicine at Mount Sinai, New York.

The results are consistent with prior evidence that the drugs are anti-inflammatory at least partly because of their interference with inflammatory pathways triggered by PCSK9 and mediated by IL-6, as described by Dr. Navarese and colleagues.

Indeed, they write, PCSK9 inhibitors may improve COVID outcomes mostly through mechanisms unrelated to LDL-receptor expression, “including direct inhibition of PCSK9-triggered inflammation.”

If true, the authors observe, it might explain “why the positive findings of the present study have not been consistently observed in trials involving other lipid-lowering agents, such as statins.” Those drugs are well-known to decrease levels of the inflammatory biomarker C-reactive protein.

In patients with stable coronary disease, in whom inflammation is typically tracked by measuring CRP, “the PCSK9 inhibitors have not been shown to have an anti-inflammatory effect,” Dr. Rosenson further explained.

But the current study’s patients with acute, severe COVID-19, a “profound inflammatory insult” with upregulation of IL-6, were “a good population” for evaluating the drugs’ potential anti-inflammatory effects, Dr. Rosenson said in an interview. The results “are quite enticing but require corroboration in a larger trial.”
 

A single injection

The IMPACT-SIRIO 5 trial entered 60 adults hospitalized with severe COVID-19 and elevated IL-6 at four centers in Poland. Patients with other known active infections were excluded.  

They were randomly assigned double-blind to receive a 140 mg injection of evolocumab (Repatha) or placebo. The 2 groups were similar with respect to demographics, body-mass index, time since symptom onset, and treatments for managing COVID-19 and its complications.

Rates of death or need for intubation at 30 days, the primary endpoint, were 23.3% in the PCSK9-inhibitor group and 53.3% for controls, a risk difference of 30% (95% confidence interval –53.4% to –6.6%). The median durations of oxygen therapy were significantly different at 13 days and 20 days, respectively, the report states.

Serum IL-6 levels fell further over 30 days in the PCSK9-inhibitor group (–56% vs. –21% among controls). A drop by more than 90% was seen in 60% of patients in the PCSK9-inhibitor group and in 27% of controls.

The average hospital stay was shorter for those getting the PCSK9 inhibitor, compared with placebo, 16 days versus 22 days, and their 30-day mortality was numerically lower, 16% versus 33.3%.

Patients’ baseline IL-6 levels above the median, the report states, had a lower mortality on the PCSK9 inhibitor versus placebo (risk difference –37.5%; 95% CI –68.2% to –6.70%).

A larger trial to corroborate these results would potentially enter similar patients hospitalized with COVID-19 with reproducible evidence of an ongoing cytokine storm, such as elevated levels of IL-6, who would be assigned to either a PCSK9 inhibitor or placebo, Dr. Rosenson proposed.

Although the current primary endpoint that combines mortality and intubation was “reasonable” for a small pilot trial, he said, if the researchers embark on a larger study, “they’ll want to look at those events separately.”

Dr. Navarese discloses receiving speaker and consultancy fees from Amgen, Sanofi-Regeneron, Bayer; and grants from Abbott. Disclosures for the other authors are in the report. Rosenson discloses receiving research funding to his institution from Amgen, Arrowhead, Eli Lilly, Novartis, and Regeneron; consulting fees from Amgen, Arrowhead, CRISPR Therapeutics, Eli Lilly, Lipigon, Novartis, Precision Biosciences, Regeneron, Ultragenyx, and Verve; speaking fees from Amgen, Kowa, and Regeneron; and royalties from Wolters Kluwer; and owning stock in MediMergent. Dr. Goonewardena reports no relevant financial relationships.

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

PCSK9 inhibitors may best be known for their powerful LDL-lowering effects but are less appreciated as anti-inflammatory agents with potential beyond cardiovascular health.

In a small pilot trial, for example, patients hospitalized with severe COVID-19 who received a single injection of PCSK9 inhibitor became less sick and more likely to survive than those given a placebo. Their 30-day risk of death or intubation fell significantly, as did their levels of the inflammatory cytokine interleukin 6 (IL-6).

Indeed, survival gains in the PCSK9-inhibitor group were greatest among patients with higher baseline concentrations of IL-6. Although the trial wasn’t powered for clinical outcomes, it suggests the drugs’ efficacy in COVID-19 tracks with intensity of inflammation, proposes a report published  in the Journal of the American College of Cardiology.

Therefore, “PCSK9 inhibition may represent a novel therapeutic pathway in addition to currently recommended therapeutic approaches for severe COVID-19,” conclude the authors, led by Eliano P. Navarese, MD, PhD, Nicolaus Copernicus University, Bydgoszcz, Poland.
 

PCSK9 inhibitors as anti-inflammatories

Although the study was small and only hypothesis-generating, the fact that outcomes for actively treated patients were proportional to baseline IL-6 levels “strongly suggests that PCSK9 inhibition can directly modulate inflammation in COVID-19,” argues an editorial accompanying the report.

The study adds to “our clinical arsenal against COVID-19,” and likely sheds light on “mechanisms through which PCSK9 inhibition dually modulates lipoprotein metabolism and inflammation,” write Sascha N. Goonewardena, MD, University of Michigan, Ann Arbor, and Robert S. Rosenson, MD, Icahn School of Medicine at Mount Sinai, New York.

The results are consistent with prior evidence that the drugs are anti-inflammatory at least partly because of their interference with inflammatory pathways triggered by PCSK9 and mediated by IL-6, as described by Dr. Navarese and colleagues.

Indeed, they write, PCSK9 inhibitors may improve COVID outcomes mostly through mechanisms unrelated to LDL-receptor expression, “including direct inhibition of PCSK9-triggered inflammation.”

If true, the authors observe, it might explain “why the positive findings of the present study have not been consistently observed in trials involving other lipid-lowering agents, such as statins.” Those drugs are well-known to decrease levels of the inflammatory biomarker C-reactive protein.

In patients with stable coronary disease, in whom inflammation is typically tracked by measuring CRP, “the PCSK9 inhibitors have not been shown to have an anti-inflammatory effect,” Dr. Rosenson further explained.

But the current study’s patients with acute, severe COVID-19, a “profound inflammatory insult” with upregulation of IL-6, were “a good population” for evaluating the drugs’ potential anti-inflammatory effects, Dr. Rosenson said in an interview. The results “are quite enticing but require corroboration in a larger trial.”
 

A single injection

The IMPACT-SIRIO 5 trial entered 60 adults hospitalized with severe COVID-19 and elevated IL-6 at four centers in Poland. Patients with other known active infections were excluded.  

They were randomly assigned double-blind to receive a 140 mg injection of evolocumab (Repatha) or placebo. The 2 groups were similar with respect to demographics, body-mass index, time since symptom onset, and treatments for managing COVID-19 and its complications.

Rates of death or need for intubation at 30 days, the primary endpoint, were 23.3% in the PCSK9-inhibitor group and 53.3% for controls, a risk difference of 30% (95% confidence interval –53.4% to –6.6%). The median durations of oxygen therapy were significantly different at 13 days and 20 days, respectively, the report states.

Serum IL-6 levels fell further over 30 days in the PCSK9-inhibitor group (–56% vs. –21% among controls). A drop by more than 90% was seen in 60% of patients in the PCSK9-inhibitor group and in 27% of controls.

The average hospital stay was shorter for those getting the PCSK9 inhibitor, compared with placebo, 16 days versus 22 days, and their 30-day mortality was numerically lower, 16% versus 33.3%.

Patients’ baseline IL-6 levels above the median, the report states, had a lower mortality on the PCSK9 inhibitor versus placebo (risk difference –37.5%; 95% CI –68.2% to –6.70%).

A larger trial to corroborate these results would potentially enter similar patients hospitalized with COVID-19 with reproducible evidence of an ongoing cytokine storm, such as elevated levels of IL-6, who would be assigned to either a PCSK9 inhibitor or placebo, Dr. Rosenson proposed.

Although the current primary endpoint that combines mortality and intubation was “reasonable” for a small pilot trial, he said, if the researchers embark on a larger study, “they’ll want to look at those events separately.”

Dr. Navarese discloses receiving speaker and consultancy fees from Amgen, Sanofi-Regeneron, Bayer; and grants from Abbott. Disclosures for the other authors are in the report. Rosenson discloses receiving research funding to his institution from Amgen, Arrowhead, Eli Lilly, Novartis, and Regeneron; consulting fees from Amgen, Arrowhead, CRISPR Therapeutics, Eli Lilly, Lipigon, Novartis, Precision Biosciences, Regeneron, Ultragenyx, and Verve; speaking fees from Amgen, Kowa, and Regeneron; and royalties from Wolters Kluwer; and owning stock in MediMergent. Dr. Goonewardena reports no relevant financial relationships.

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

PCSK9 inhibitors may best be known for their powerful LDL-lowering effects but are less appreciated as anti-inflammatory agents with potential beyond cardiovascular health.

In a small pilot trial, for example, patients hospitalized with severe COVID-19 who received a single injection of PCSK9 inhibitor became less sick and more likely to survive than those given a placebo. Their 30-day risk of death or intubation fell significantly, as did their levels of the inflammatory cytokine interleukin 6 (IL-6).

Indeed, survival gains in the PCSK9-inhibitor group were greatest among patients with higher baseline concentrations of IL-6. Although the trial wasn’t powered for clinical outcomes, it suggests the drugs’ efficacy in COVID-19 tracks with intensity of inflammation, proposes a report published  in the Journal of the American College of Cardiology.

Therefore, “PCSK9 inhibition may represent a novel therapeutic pathway in addition to currently recommended therapeutic approaches for severe COVID-19,” conclude the authors, led by Eliano P. Navarese, MD, PhD, Nicolaus Copernicus University, Bydgoszcz, Poland.
 

PCSK9 inhibitors as anti-inflammatories

Although the study was small and only hypothesis-generating, the fact that outcomes for actively treated patients were proportional to baseline IL-6 levels “strongly suggests that PCSK9 inhibition can directly modulate inflammation in COVID-19,” argues an editorial accompanying the report.

The study adds to “our clinical arsenal against COVID-19,” and likely sheds light on “mechanisms through which PCSK9 inhibition dually modulates lipoprotein metabolism and inflammation,” write Sascha N. Goonewardena, MD, University of Michigan, Ann Arbor, and Robert S. Rosenson, MD, Icahn School of Medicine at Mount Sinai, New York.

The results are consistent with prior evidence that the drugs are anti-inflammatory at least partly because of their interference with inflammatory pathways triggered by PCSK9 and mediated by IL-6, as described by Dr. Navarese and colleagues.

Indeed, they write, PCSK9 inhibitors may improve COVID outcomes mostly through mechanisms unrelated to LDL-receptor expression, “including direct inhibition of PCSK9-triggered inflammation.”

If true, the authors observe, it might explain “why the positive findings of the present study have not been consistently observed in trials involving other lipid-lowering agents, such as statins.” Those drugs are well-known to decrease levels of the inflammatory biomarker C-reactive protein.

In patients with stable coronary disease, in whom inflammation is typically tracked by measuring CRP, “the PCSK9 inhibitors have not been shown to have an anti-inflammatory effect,” Dr. Rosenson further explained.

But the current study’s patients with acute, severe COVID-19, a “profound inflammatory insult” with upregulation of IL-6, were “a good population” for evaluating the drugs’ potential anti-inflammatory effects, Dr. Rosenson said in an interview. The results “are quite enticing but require corroboration in a larger trial.”
 

A single injection

The IMPACT-SIRIO 5 trial entered 60 adults hospitalized with severe COVID-19 and elevated IL-6 at four centers in Poland. Patients with other known active infections were excluded.  

They were randomly assigned double-blind to receive a 140 mg injection of evolocumab (Repatha) or placebo. The 2 groups were similar with respect to demographics, body-mass index, time since symptom onset, and treatments for managing COVID-19 and its complications.

Rates of death or need for intubation at 30 days, the primary endpoint, were 23.3% in the PCSK9-inhibitor group and 53.3% for controls, a risk difference of 30% (95% confidence interval –53.4% to –6.6%). The median durations of oxygen therapy were significantly different at 13 days and 20 days, respectively, the report states.

Serum IL-6 levels fell further over 30 days in the PCSK9-inhibitor group (–56% vs. –21% among controls). A drop by more than 90% was seen in 60% of patients in the PCSK9-inhibitor group and in 27% of controls.

The average hospital stay was shorter for those getting the PCSK9 inhibitor, compared with placebo, 16 days versus 22 days, and their 30-day mortality was numerically lower, 16% versus 33.3%.

Patients’ baseline IL-6 levels above the median, the report states, had a lower mortality on the PCSK9 inhibitor versus placebo (risk difference –37.5%; 95% CI –68.2% to –6.70%).

A larger trial to corroborate these results would potentially enter similar patients hospitalized with COVID-19 with reproducible evidence of an ongoing cytokine storm, such as elevated levels of IL-6, who would be assigned to either a PCSK9 inhibitor or placebo, Dr. Rosenson proposed.

Although the current primary endpoint that combines mortality and intubation was “reasonable” for a small pilot trial, he said, if the researchers embark on a larger study, “they’ll want to look at those events separately.”

Dr. Navarese discloses receiving speaker and consultancy fees from Amgen, Sanofi-Regeneron, Bayer; and grants from Abbott. Disclosures for the other authors are in the report. Rosenson discloses receiving research funding to his institution from Amgen, Arrowhead, Eli Lilly, Novartis, and Regeneron; consulting fees from Amgen, Arrowhead, CRISPR Therapeutics, Eli Lilly, Lipigon, Novartis, Precision Biosciences, Regeneron, Ultragenyx, and Verve; speaking fees from Amgen, Kowa, and Regeneron; and royalties from Wolters Kluwer; and owning stock in MediMergent. Dr. Goonewardena reports no relevant financial relationships.

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

To the Editor:

Microneedling is a percutaneous collagen induction therapy frequently used in cosmetic dermatology to promote skin rejuvenation and hair growth and to treat scars by taking advantage of the body’s natural wound-healing cascade.¹ The procedure works by generating thousands of microscopic wounds in the dermis with minimal damage to the epidermis, thus initiating the wound-healing cascade and subsequently promoting collagen production in a manner safe for all Fitzpatrick classification skin types.^1-3 This therapy effectively treats scars by breaking down scarred collagen and replacing it with new healthy collagen. Microneedling also has application in drug delivery by increasing the permeability of the skin; the microwounds generated can serve as a portal for drug delivery.⁴

Bimatoprost is a prostaglandin analogue typically used to treat hypotrichosis and open-angle glaucoma.^5-7 A known side effect of bimatoprost is hyperpigmentation of surrounding skin; the drug increases melanogenesis, melanocyte proliferation, and melanocyte dendricity, resulting in activation of the inflammatory response and subsequent prostaglandin release, which stimulates melanogenesis. This effect is similar to UV radiation–induced inflammation and hyperpigmentation.^6,8

Capitalizing on this effect, a novel application of bimatoprost has been proposed—treating vitiligo, in which hypopigmentation results from destruction of melanocytes in certain areas of the skin. Bimatoprost ophthalmic solution 0.3% utilized as an off-label treatment for vitiligo has been shown to notably increase melanogenesis and return pigmentation to hypopigmented areas.^8-10

A 32-year-old Black woman presented to our clinic with a 40×15-cm scar that was marked by postinflammatory hypopigmentation from a second-degree burn on the right proximal arm. The patient had been burned 5 months prior by boiling water that was spilled on the arm while cooking. She had immediately sought treatment at an emergency department and subsequently in a burn unit, where the burn was debrided twice; medication was not prescribed to continue treatment. The patient reported that the scarring and hypopigmentation had taken a psychologic toll; her hope was to have pigmentation restored to the affected area to boost her confidence.

Physical examination revealed that the burn wound had healed but visible scarring and severe hypopigmentation due to destroyed melanocytes remained (Figure 1). To inhibit inflammation and stimulate repigmentation, we prescribed the calcineurin inhibitor tacrolimus ointment 0.1% to be applied daily to the affected area. The patient returned to the clinic 1 month later. Perifollicular hyperpigmentation was noted at the site of the scar.

Monthly microneedling sessions with bimatoprost ophthalmic solution 0.3% were started. To avoid damaging any potentially remaining unhealed hypodermis and vasculature, the first microneedling session was performed with 9 needles set at minimal needle depth and frequency. The number of needles and their depth and frequency gradually were increased with each subsequent treatment. The patient continued tacrolimus ointment 0.1% throughout the course of treatment.

For each microneedling procedure, a handheld motorized microneedling device was applied to the skin at a depth of 0.25 mm, which was gradually increased until pinpoint petechiae were achieved. Bimatoprost ophthalmic solution 0.3% was then painted on the skin and allowed to absorb. Microneedling was performed again, ensuring that bimatoprost entered the skin in the area of the burn scar.

Microneedling procedures were performed monthly for 6 months, then once 3 months later, and once more 3 months later—8 treatments in total over the course of 1 year. Improvement in skin pigmentation was noted at each visit (Figure 2). Repigmentation was first noticed surrounding hair follicles; after later visits, it was observed that pigmentation began to spread from hair follicles to fill in remaining skin. The darkest areas of pigmentation were first noted around hair follicles; over time, melanocytes appeared to spontaneously regenerate and fill in surrounding areas as the scar continued to heal. The patient continued use of tacrolimus during the entire course of microneedling treatments and for the following 4 months. Sixteen months after initiation of treatment, the appearance of the skin was texturally smooth and returned to almost its original pigmentation (Figure 3).

We report a successful outcome in a patient with a hypopigmented burn scar who was treated with bimatoprost administered with traditional microneedling and alongside a tacrolimus regimen. Tacrolimus ointment inhibited the inflammatory response to allow melanocytes to heal and regenerate; bimatoprost and microneedling promoted hyperpigmentation of hair follicles in the affected area, eventually restoring pigmentation to the entire area. Our patient was extremely satisfied with the results of this combination treatment. She has reported feeling more confident going out and wearing short-sleeved clothing. Percutaneous drug delivery of bimatoprost ophthalmic solution 0.3% combined with topical tacrolimus may be an effective treatment for skin repigmentation. Further investigation of this regimen is needed to develop standardized treatment protocols.

To the Editor:

Microneedling is a percutaneous collagen induction therapy frequently used in cosmetic dermatology to promote skin rejuvenation and hair growth and to treat scars by taking advantage of the body’s natural wound-healing cascade.¹ The procedure works by generating thousands of microscopic wounds in the dermis with minimal damage to the epidermis, thus initiating the wound-healing cascade and subsequently promoting collagen production in a manner safe for all Fitzpatrick classification skin types.^1-3 This therapy effectively treats scars by breaking down scarred collagen and replacing it with new healthy collagen. Microneedling also has application in drug delivery by increasing the permeability of the skin; the microwounds generated can serve as a portal for drug delivery.⁴

Bimatoprost is a prostaglandin analogue typically used to treat hypotrichosis and open-angle glaucoma.^5-7 A known side effect of bimatoprost is hyperpigmentation of surrounding skin; the drug increases melanogenesis, melanocyte proliferation, and melanocyte dendricity, resulting in activation of the inflammatory response and subsequent prostaglandin release, which stimulates melanogenesis. This effect is similar to UV radiation–induced inflammation and hyperpigmentation.^6,8

Capitalizing on this effect, a novel application of bimatoprost has been proposed—treating vitiligo, in which hypopigmentation results from destruction of melanocytes in certain areas of the skin. Bimatoprost ophthalmic solution 0.3% utilized as an off-label treatment for vitiligo has been shown to notably increase melanogenesis and return pigmentation to hypopigmented areas.^8-10

A 32-year-old Black woman presented to our clinic with a 40×15-cm scar that was marked by postinflammatory hypopigmentation from a second-degree burn on the right proximal arm. The patient had been burned 5 months prior by boiling water that was spilled on the arm while cooking. She had immediately sought treatment at an emergency department and subsequently in a burn unit, where the burn was debrided twice; medication was not prescribed to continue treatment. The patient reported that the scarring and hypopigmentation had taken a psychologic toll; her hope was to have pigmentation restored to the affected area to boost her confidence.

Physical examination revealed that the burn wound had healed but visible scarring and severe hypopigmentation due to destroyed melanocytes remained (Figure 1). To inhibit inflammation and stimulate repigmentation, we prescribed the calcineurin inhibitor tacrolimus ointment 0.1% to be applied daily to the affected area. The patient returned to the clinic 1 month later. Perifollicular hyperpigmentation was noted at the site of the scar.

Monthly microneedling sessions with bimatoprost ophthalmic solution 0.3% were started. To avoid damaging any potentially remaining unhealed hypodermis and vasculature, the first microneedling session was performed with 9 needles set at minimal needle depth and frequency. The number of needles and their depth and frequency gradually were increased with each subsequent treatment. The patient continued tacrolimus ointment 0.1% throughout the course of treatment.

For each microneedling procedure, a handheld motorized microneedling device was applied to the skin at a depth of 0.25 mm, which was gradually increased until pinpoint petechiae were achieved. Bimatoprost ophthalmic solution 0.3% was then painted on the skin and allowed to absorb. Microneedling was performed again, ensuring that bimatoprost entered the skin in the area of the burn scar.

Microneedling procedures were performed monthly for 6 months, then once 3 months later, and once more 3 months later—8 treatments in total over the course of 1 year. Improvement in skin pigmentation was noted at each visit (Figure 2). Repigmentation was first noticed surrounding hair follicles; after later visits, it was observed that pigmentation began to spread from hair follicles to fill in remaining skin. The darkest areas of pigmentation were first noted around hair follicles; over time, melanocytes appeared to spontaneously regenerate and fill in surrounding areas as the scar continued to heal. The patient continued use of tacrolimus during the entire course of microneedling treatments and for the following 4 months. Sixteen months after initiation of treatment, the appearance of the skin was texturally smooth and returned to almost its original pigmentation (Figure 3).

We report a successful outcome in a patient with a hypopigmented burn scar who was treated with bimatoprost administered with traditional microneedling and alongside a tacrolimus regimen. Tacrolimus ointment inhibited the inflammatory response to allow melanocytes to heal and regenerate; bimatoprost and microneedling promoted hyperpigmentation of hair follicles in the affected area, eventually restoring pigmentation to the entire area. Our patient was extremely satisfied with the results of this combination treatment. She has reported feeling more confident going out and wearing short-sleeved clothing. Percutaneous drug delivery of bimatoprost ophthalmic solution 0.3% combined with topical tacrolimus may be an effective treatment for skin repigmentation. Further investigation of this regimen is needed to develop standardized treatment protocols.

To the Editor:

Microneedling is a percutaneous collagen induction therapy frequently used in cosmetic dermatology to promote skin rejuvenation and hair growth and to treat scars by taking advantage of the body’s natural wound-healing cascade.¹ The procedure works by generating thousands of microscopic wounds in the dermis with minimal damage to the epidermis, thus initiating the wound-healing cascade and subsequently promoting collagen production in a manner safe for all Fitzpatrick classification skin types.^1-3 This therapy effectively treats scars by breaking down scarred collagen and replacing it with new healthy collagen. Microneedling also has application in drug delivery by increasing the permeability of the skin; the microwounds generated can serve as a portal for drug delivery.⁴

Bimatoprost is a prostaglandin analogue typically used to treat hypotrichosis and open-angle glaucoma.^5-7 A known side effect of bimatoprost is hyperpigmentation of surrounding skin; the drug increases melanogenesis, melanocyte proliferation, and melanocyte dendricity, resulting in activation of the inflammatory response and subsequent prostaglandin release, which stimulates melanogenesis. This effect is similar to UV radiation–induced inflammation and hyperpigmentation.^6,8

Capitalizing on this effect, a novel application of bimatoprost has been proposed—treating vitiligo, in which hypopigmentation results from destruction of melanocytes in certain areas of the skin. Bimatoprost ophthalmic solution 0.3% utilized as an off-label treatment for vitiligo has been shown to notably increase melanogenesis and return pigmentation to hypopigmented areas.^8-10

A 32-year-old Black woman presented to our clinic with a 40×15-cm scar that was marked by postinflammatory hypopigmentation from a second-degree burn on the right proximal arm. The patient had been burned 5 months prior by boiling water that was spilled on the arm while cooking. She had immediately sought treatment at an emergency department and subsequently in a burn unit, where the burn was debrided twice; medication was not prescribed to continue treatment. The patient reported that the scarring and hypopigmentation had taken a psychologic toll; her hope was to have pigmentation restored to the affected area to boost her confidence.

Physical examination revealed that the burn wound had healed but visible scarring and severe hypopigmentation due to destroyed melanocytes remained (Figure 1). To inhibit inflammation and stimulate repigmentation, we prescribed the calcineurin inhibitor tacrolimus ointment 0.1% to be applied daily to the affected area. The patient returned to the clinic 1 month later. Perifollicular hyperpigmentation was noted at the site of the scar.

Monthly microneedling sessions with bimatoprost ophthalmic solution 0.3% were started. To avoid damaging any potentially remaining unhealed hypodermis and vasculature, the first microneedling session was performed with 9 needles set at minimal needle depth and frequency. The number of needles and their depth and frequency gradually were increased with each subsequent treatment. The patient continued tacrolimus ointment 0.1% throughout the course of treatment.

For each microneedling procedure, a handheld motorized microneedling device was applied to the skin at a depth of 0.25 mm, which was gradually increased until pinpoint petechiae were achieved. Bimatoprost ophthalmic solution 0.3% was then painted on the skin and allowed to absorb. Microneedling was performed again, ensuring that bimatoprost entered the skin in the area of the burn scar.

Microneedling procedures were performed monthly for 6 months, then once 3 months later, and once more 3 months later—8 treatments in total over the course of 1 year. Improvement in skin pigmentation was noted at each visit (Figure 2). Repigmentation was first noticed surrounding hair follicles; after later visits, it was observed that pigmentation began to spread from hair follicles to fill in remaining skin. The darkest areas of pigmentation were first noted around hair follicles; over time, melanocytes appeared to spontaneously regenerate and fill in surrounding areas as the scar continued to heal. The patient continued use of tacrolimus during the entire course of microneedling treatments and for the following 4 months. Sixteen months after initiation of treatment, the appearance of the skin was texturally smooth and returned to almost its original pigmentation (Figure 3).

We report a successful outcome in a patient with a hypopigmented burn scar who was treated with bimatoprost administered with traditional microneedling and alongside a tacrolimus regimen. Tacrolimus ointment inhibited the inflammatory response to allow melanocytes to heal and regenerate; bimatoprost and microneedling promoted hyperpigmentation of hair follicles in the affected area, eventually restoring pigmentation to the entire area. Our patient was extremely satisfied with the results of this combination treatment. She has reported feeling more confident going out and wearing short-sleeved clothing. Percutaneous drug delivery of bimatoprost ophthalmic solution 0.3% combined with topical tacrolimus may be an effective treatment for skin repigmentation. Further investigation of this regimen is needed to develop standardized treatment protocols.

The American College of Physicians has issued new guidelines for managing acute major depressive disorder, suggesting those with moderate to severe depression may start with cognitive-behavioral therapy (CBT) alone or a second-generation antidepressant (SGA) alone.

The guidelines also state that patients with mild depression should start with CBT alone, and if a patient with moderate to severe depression prefers, they can use a combination of both CBT and an SGA.

These nuanced recommendations contrast sharply with the 2016 ACP guidelines for depression, which lumped all stages and severity levels together, and came with just one recommendation: Clinicians should choose between CBT and an SGA.

More data have come to light over the years, requiring the present update, reported lead author Amir Qaseem, MD, PhD, vice president of Clinical Policy and the Center for Evidence Reviews at the ACP, and adjunct faculty at Thomas Jefferson University, Philadelphia, and colleagues.

In addition to the focus on acute depression, Dr. Qaseem and colleagues highlighted the new guidelines' “consideration of patient values and preferences, and costs,” as well as responses to therapy.

Recommendations were derived from a network meta-analysis that included studies evaluating nonpharmacologic and pharmacologic therapies, the authors wrote in Annals of Internal Medicine. They compared effectiveness across a range of SGAs, “including selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; and others such as bupropion, mirtazapine, nefazodone, trazodone, vilazodone, and vortioxetine.”

This analysis yielded three pieces of clinical advice.

First, patients in the acute phase of mild depression should receive CBT alone as their initial treatment.

Dr. Qaseem and colleagues noted that many depression studies for pharmacologic therapies excluded these patients in favor of those with moderate to severe depression, leaving an evidence gap.

“Furthermore, the Clinical Guidelines Committee had concerns about adverse effects of SGAs in these patients and suggests that the use of SGAs as initial treatment of these patients should be based on additional considerations, such as limited access to or cost of CBT, history of moderate or severe major depressive disorder, or patient preferences,” they added.

The committee’s next recommendation, based on moderate-certainty evidence, suggested that CBT alone or an SGA alone should be considered for patients in the acute phase of moderate to severe depression. This call for monotherapy is balanced by a conditional recommendation based on low-certainty evidence that the same group may benefit from initial combination therapy with both CBT and an SGA.

“The informed decision on the options of monotherapy with CBT versus SGAs, or combination therapy, should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients’ specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences,” the guidelines state.

The third and final recommendation offers an algorithm for patients who do not respond to initial therapy with an SGA. Multiple pathways are provided: Switch to CBT or augment with CBT; or switch to a different SGA or augment with a second pharmacologic therapy, such as mirtazapine, bupropion, or buspirone.

“These second-line treatment strategies show similar efficacy when compared with each other,” the guidelines committee noted.

Again, the guidelines suggest that second-line choices should be personalized based on the various factors previously discussed.

A timely update

“The new guideline is very different from the last guideline,” said Ryan Mire, MD, president of the ACP and practicing internal medicine physician in Nashville, Tenn. in a written comment. “ACP decided to update the depression guidelines with a focus on acute depression because approximately 70% of patients with major depressive disorder do not achieve remission and remain in the acute phase after the initial pharmacologic treatment attempt. In addition, there is new evidence on second-line treatments since the 2016 ACP guideline was published.”

Neil S. Skolnik, MD, of Thomas Jefferson University, Philadelphia, agreed that the guidelines offer a necessary and fresh perspective on caring for patients with depression.

“These guidelines are a helpful update, assuring us that we are using the latest, evidence-based therapies, and [they] are written in a practical, easy-to-implement manner,” Dr. Skolnik said in a written comment.

“First, the guidelines reaffirm that CBT is an effective first-line option, with or without the concurrent use of an SGA,” Dr. Skolnik said, noting that CBT alone may reduce likelihood of recurrence, compared with an SGA alone. “Many patients do not like the idea of medication, or the potential side effects of medications, and CBT is an evidenced-based approach that can be very helpful for patients.”

Dr. Skolnik also applauded the guidelines authors for offering a clear path forward for patients who do not have full remission after treatment – a common clinical scenario.

Valuable despite the gaps

Other experts expressed mixed impressions of the update, noting both highs and lows.

“Although [this guideline] has some gaps, it is more valuable in several ways than other widely consulted practice guidelines for depression,” wrote Miriam Shuchman, MD and Elia Abi-Jaoude, MSc, MD, PhD, of the University of Toronto, in an accompanying editorial.

Specifically, they praised the publication’s focus on shared decision-making in the treatment planning process.

“This effort to respond to patient preferences is crucial and may even increase the chance that patients will improve with treatment,” they wrote.

They also applauded the ACP’s efforts to recuse any committee members who may have had conflicts of interest “that could affect their judgment about treatments for depression.”

After highlighting these attributes, Dr. Shuchman and Dr. Abi-Jaoude noted that the guidelines still contain “significant gaps.”

Foremost, they pointed out the guidelines' emphasis on CBT to the exclusion of other nonpharmacologic options.

“The guideline does patients a disservice by leaving out several nonmedication treatment options that clinicians can offer as first- or second-line therapies,” they wrote.

This oversight may increase risk that patients simply hop from one SGA to another, which is a common, and often ineffective, strategy, according to Dr. Shuchman and Dr. Abi-Jaoude.

“Patients often go from one drug to the next in the hopes of landing on one that ‘works,’ ” the editorialists wrote. “This narrow clinical approach of pursuing medication-based treatments ignores the ways difficulties in a person’s work or relationships may contribute to their struggles with depression. At a time when the COVID-19 pandemic has underscored the importance of the social context of mental health, clinicians may need to consider other forms of support and tailor prescribing to what is most relevant and accessible for a particular patient.”

Dr. Shuchman and Dr. Abi-Jaoude went on to suggest several nonpharmacologic options beyond CBT, including interpersonal therapy, psychodynamic therapy, problem solving, behavioral activation, and guided self-help.

The other key gap they pointed out relates to withdrawal.

Although the guideline does advise physicians to taper antidepressants to reduce risk of withdrawal, the editorialists suggested that this recommendation lacked sufficient emphasis, as it can be a particularly difficult period in the treatment process.

“Tapering of an antidepressant may need to be done over months or years, not weeks, and a patient may need to visit a compounding pharmacy to obtain doses of a second-generation antidepressant not marketed by drug manufacturers so that prescriptions can be tapered even more slowly,” they suggested.

Financial costs remain unclear

Beyond the above medical considerations, one other piece of the depression puzzle remains unsolved: cost.

In a simultaneously published rapid review, Andreea Dobrescu, MD, PhD, of Cochrane Austria, and colleagues evaluated the relative cost-effectiveness of first- and second-step treatment strategies.

For most comparisons, evidence was insufficient to reach a conclusion, although they suggested that CBT may be more cost effective at the 5-year mark.

“For most pharmacologic and nonpharmacologic interventions for major depressive disorder, evidence was missing or was insufficient to draw conclusions about the cost-effectiveness of first- or second-step treatments for MDD,” Dr. Dobrescu and colleagues wrote. “The strongest evidence (albeit still low certainty of evidence) was for the cost-effectiveness of CBT compared with SGA as a first-step treatment over a 5-year time horizon from the societal and health care sector perspectives. However, this evidence should also be interpreted cautiously considering it is based on a single study.”

When asked about the financial findings, Dr. Mire agreed that more data are needed, especially because CBT and SGA costs range widely. He suggested that cost, for each patient, should be considered in the personalized approach now highlighted by the new guidelines.

The guidelines and the Cochrane cost-effectiveness study were supported by the ACP. The guidelines' authors and other individuals quoted in this article reported no conflicts of interest.

The American College of Physicians has issued new guidelines for managing acute major depressive disorder, suggesting those with moderate to severe depression may start with cognitive-behavioral therapy (CBT) alone or a second-generation antidepressant (SGA) alone.

The guidelines also state that patients with mild depression should start with CBT alone, and if a patient with moderate to severe depression prefers, they can use a combination of both CBT and an SGA.

These nuanced recommendations contrast sharply with the 2016 ACP guidelines for depression, which lumped all stages and severity levels together, and came with just one recommendation: Clinicians should choose between CBT and an SGA.

More data have come to light over the years, requiring the present update, reported lead author Amir Qaseem, MD, PhD, vice president of Clinical Policy and the Center for Evidence Reviews at the ACP, and adjunct faculty at Thomas Jefferson University, Philadelphia, and colleagues.

In addition to the focus on acute depression, Dr. Qaseem and colleagues highlighted the new guidelines' “consideration of patient values and preferences, and costs,” as well as responses to therapy.

Recommendations were derived from a network meta-analysis that included studies evaluating nonpharmacologic and pharmacologic therapies, the authors wrote in Annals of Internal Medicine. They compared effectiveness across a range of SGAs, “including selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; and others such as bupropion, mirtazapine, nefazodone, trazodone, vilazodone, and vortioxetine.”

This analysis yielded three pieces of clinical advice.

First, patients in the acute phase of mild depression should receive CBT alone as their initial treatment.

Dr. Qaseem and colleagues noted that many depression studies for pharmacologic therapies excluded these patients in favor of those with moderate to severe depression, leaving an evidence gap.

“Furthermore, the Clinical Guidelines Committee had concerns about adverse effects of SGAs in these patients and suggests that the use of SGAs as initial treatment of these patients should be based on additional considerations, such as limited access to or cost of CBT, history of moderate or severe major depressive disorder, or patient preferences,” they added.

The committee’s next recommendation, based on moderate-certainty evidence, suggested that CBT alone or an SGA alone should be considered for patients in the acute phase of moderate to severe depression. This call for monotherapy is balanced by a conditional recommendation based on low-certainty evidence that the same group may benefit from initial combination therapy with both CBT and an SGA.

“The informed decision on the options of monotherapy with CBT versus SGAs, or combination therapy, should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients’ specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences,” the guidelines state.

The third and final recommendation offers an algorithm for patients who do not respond to initial therapy with an SGA. Multiple pathways are provided: Switch to CBT or augment with CBT; or switch to a different SGA or augment with a second pharmacologic therapy, such as mirtazapine, bupropion, or buspirone.

“These second-line treatment strategies show similar efficacy when compared with each other,” the guidelines committee noted.

Again, the guidelines suggest that second-line choices should be personalized based on the various factors previously discussed.

A timely update

“The new guideline is very different from the last guideline,” said Ryan Mire, MD, president of the ACP and practicing internal medicine physician in Nashville, Tenn. in a written comment. “ACP decided to update the depression guidelines with a focus on acute depression because approximately 70% of patients with major depressive disorder do not achieve remission and remain in the acute phase after the initial pharmacologic treatment attempt. In addition, there is new evidence on second-line treatments since the 2016 ACP guideline was published.”

Neil S. Skolnik, MD, of Thomas Jefferson University, Philadelphia, agreed that the guidelines offer a necessary and fresh perspective on caring for patients with depression.

“These guidelines are a helpful update, assuring us that we are using the latest, evidence-based therapies, and [they] are written in a practical, easy-to-implement manner,” Dr. Skolnik said in a written comment.

“First, the guidelines reaffirm that CBT is an effective first-line option, with or without the concurrent use of an SGA,” Dr. Skolnik said, noting that CBT alone may reduce likelihood of recurrence, compared with an SGA alone. “Many patients do not like the idea of medication, or the potential side effects of medications, and CBT is an evidenced-based approach that can be very helpful for patients.”

Dr. Skolnik also applauded the guidelines authors for offering a clear path forward for patients who do not have full remission after treatment – a common clinical scenario.

Valuable despite the gaps

Other experts expressed mixed impressions of the update, noting both highs and lows.

“Although [this guideline] has some gaps, it is more valuable in several ways than other widely consulted practice guidelines for depression,” wrote Miriam Shuchman, MD and Elia Abi-Jaoude, MSc, MD, PhD, of the University of Toronto, in an accompanying editorial.

Specifically, they praised the publication’s focus on shared decision-making in the treatment planning process.

“This effort to respond to patient preferences is crucial and may even increase the chance that patients will improve with treatment,” they wrote.

They also applauded the ACP’s efforts to recuse any committee members who may have had conflicts of interest “that could affect their judgment about treatments for depression.”

After highlighting these attributes, Dr. Shuchman and Dr. Abi-Jaoude noted that the guidelines still contain “significant gaps.”

Foremost, they pointed out the guidelines' emphasis on CBT to the exclusion of other nonpharmacologic options.

“The guideline does patients a disservice by leaving out several nonmedication treatment options that clinicians can offer as first- or second-line therapies,” they wrote.

This oversight may increase risk that patients simply hop from one SGA to another, which is a common, and often ineffective, strategy, according to Dr. Shuchman and Dr. Abi-Jaoude.

“Patients often go from one drug to the next in the hopes of landing on one that ‘works,’ ” the editorialists wrote. “This narrow clinical approach of pursuing medication-based treatments ignores the ways difficulties in a person’s work or relationships may contribute to their struggles with depression. At a time when the COVID-19 pandemic has underscored the importance of the social context of mental health, clinicians may need to consider other forms of support and tailor prescribing to what is most relevant and accessible for a particular patient.”

Dr. Shuchman and Dr. Abi-Jaoude went on to suggest several nonpharmacologic options beyond CBT, including interpersonal therapy, psychodynamic therapy, problem solving, behavioral activation, and guided self-help.

The other key gap they pointed out relates to withdrawal.

Although the guideline does advise physicians to taper antidepressants to reduce risk of withdrawal, the editorialists suggested that this recommendation lacked sufficient emphasis, as it can be a particularly difficult period in the treatment process.

“Tapering of an antidepressant may need to be done over months or years, not weeks, and a patient may need to visit a compounding pharmacy to obtain doses of a second-generation antidepressant not marketed by drug manufacturers so that prescriptions can be tapered even more slowly,” they suggested.

Financial costs remain unclear

Beyond the above medical considerations, one other piece of the depression puzzle remains unsolved: cost.

In a simultaneously published rapid review, Andreea Dobrescu, MD, PhD, of Cochrane Austria, and colleagues evaluated the relative cost-effectiveness of first- and second-step treatment strategies.

For most comparisons, evidence was insufficient to reach a conclusion, although they suggested that CBT may be more cost effective at the 5-year mark.

“For most pharmacologic and nonpharmacologic interventions for major depressive disorder, evidence was missing or was insufficient to draw conclusions about the cost-effectiveness of first- or second-step treatments for MDD,” Dr. Dobrescu and colleagues wrote. “The strongest evidence (albeit still low certainty of evidence) was for the cost-effectiveness of CBT compared with SGA as a first-step treatment over a 5-year time horizon from the societal and health care sector perspectives. However, this evidence should also be interpreted cautiously considering it is based on a single study.”

When asked about the financial findings, Dr. Mire agreed that more data are needed, especially because CBT and SGA costs range widely. He suggested that cost, for each patient, should be considered in the personalized approach now highlighted by the new guidelines.

The guidelines and the Cochrane cost-effectiveness study were supported by the ACP. The guidelines' authors and other individuals quoted in this article reported no conflicts of interest.

The American College of Physicians has issued new guidelines for managing acute major depressive disorder, suggesting those with moderate to severe depression may start with cognitive-behavioral therapy (CBT) alone or a second-generation antidepressant (SGA) alone.

The guidelines also state that patients with mild depression should start with CBT alone, and if a patient with moderate to severe depression prefers, they can use a combination of both CBT and an SGA.

These nuanced recommendations contrast sharply with the 2016 ACP guidelines for depression, which lumped all stages and severity levels together, and came with just one recommendation: Clinicians should choose between CBT and an SGA.

More data have come to light over the years, requiring the present update, reported lead author Amir Qaseem, MD, PhD, vice president of Clinical Policy and the Center for Evidence Reviews at the ACP, and adjunct faculty at Thomas Jefferson University, Philadelphia, and colleagues.

In addition to the focus on acute depression, Dr. Qaseem and colleagues highlighted the new guidelines' “consideration of patient values and preferences, and costs,” as well as responses to therapy.

Recommendations were derived from a network meta-analysis that included studies evaluating nonpharmacologic and pharmacologic therapies, the authors wrote in Annals of Internal Medicine. They compared effectiveness across a range of SGAs, “including selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; and others such as bupropion, mirtazapine, nefazodone, trazodone, vilazodone, and vortioxetine.”

This analysis yielded three pieces of clinical advice.

First, patients in the acute phase of mild depression should receive CBT alone as their initial treatment.

Dr. Qaseem and colleagues noted that many depression studies for pharmacologic therapies excluded these patients in favor of those with moderate to severe depression, leaving an evidence gap.

“Furthermore, the Clinical Guidelines Committee had concerns about adverse effects of SGAs in these patients and suggests that the use of SGAs as initial treatment of these patients should be based on additional considerations, such as limited access to or cost of CBT, history of moderate or severe major depressive disorder, or patient preferences,” they added.

The committee’s next recommendation, based on moderate-certainty evidence, suggested that CBT alone or an SGA alone should be considered for patients in the acute phase of moderate to severe depression. This call for monotherapy is balanced by a conditional recommendation based on low-certainty evidence that the same group may benefit from initial combination therapy with both CBT and an SGA.

“The informed decision on the options of monotherapy with CBT versus SGAs, or combination therapy, should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients’ specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences,” the guidelines state.

The third and final recommendation offers an algorithm for patients who do not respond to initial therapy with an SGA. Multiple pathways are provided: Switch to CBT or augment with CBT; or switch to a different SGA or augment with a second pharmacologic therapy, such as mirtazapine, bupropion, or buspirone.

“These second-line treatment strategies show similar efficacy when compared with each other,” the guidelines committee noted.

Again, the guidelines suggest that second-line choices should be personalized based on the various factors previously discussed.

A timely update

“The new guideline is very different from the last guideline,” said Ryan Mire, MD, president of the ACP and practicing internal medicine physician in Nashville, Tenn. in a written comment. “ACP decided to update the depression guidelines with a focus on acute depression because approximately 70% of patients with major depressive disorder do not achieve remission and remain in the acute phase after the initial pharmacologic treatment attempt. In addition, there is new evidence on second-line treatments since the 2016 ACP guideline was published.”

Neil S. Skolnik, MD, of Thomas Jefferson University, Philadelphia, agreed that the guidelines offer a necessary and fresh perspective on caring for patients with depression.

“These guidelines are a helpful update, assuring us that we are using the latest, evidence-based therapies, and [they] are written in a practical, easy-to-implement manner,” Dr. Skolnik said in a written comment.

“First, the guidelines reaffirm that CBT is an effective first-line option, with or without the concurrent use of an SGA,” Dr. Skolnik said, noting that CBT alone may reduce likelihood of recurrence, compared with an SGA alone. “Many patients do not like the idea of medication, or the potential side effects of medications, and CBT is an evidenced-based approach that can be very helpful for patients.”

Dr. Skolnik also applauded the guidelines authors for offering a clear path forward for patients who do not have full remission after treatment – a common clinical scenario.

Valuable despite the gaps

Other experts expressed mixed impressions of the update, noting both highs and lows.

“Although [this guideline] has some gaps, it is more valuable in several ways than other widely consulted practice guidelines for depression,” wrote Miriam Shuchman, MD and Elia Abi-Jaoude, MSc, MD, PhD, of the University of Toronto, in an accompanying editorial.

Specifically, they praised the publication’s focus on shared decision-making in the treatment planning process.

“This effort to respond to patient preferences is crucial and may even increase the chance that patients will improve with treatment,” they wrote.

They also applauded the ACP’s efforts to recuse any committee members who may have had conflicts of interest “that could affect their judgment about treatments for depression.”

After highlighting these attributes, Dr. Shuchman and Dr. Abi-Jaoude noted that the guidelines still contain “significant gaps.”

Foremost, they pointed out the guidelines' emphasis on CBT to the exclusion of other nonpharmacologic options.

“The guideline does patients a disservice by leaving out several nonmedication treatment options that clinicians can offer as first- or second-line therapies,” they wrote.

This oversight may increase risk that patients simply hop from one SGA to another, which is a common, and often ineffective, strategy, according to Dr. Shuchman and Dr. Abi-Jaoude.

“Patients often go from one drug to the next in the hopes of landing on one that ‘works,’ ” the editorialists wrote. “This narrow clinical approach of pursuing medication-based treatments ignores the ways difficulties in a person’s work or relationships may contribute to their struggles with depression. At a time when the COVID-19 pandemic has underscored the importance of the social context of mental health, clinicians may need to consider other forms of support and tailor prescribing to what is most relevant and accessible for a particular patient.”

Dr. Shuchman and Dr. Abi-Jaoude went on to suggest several nonpharmacologic options beyond CBT, including interpersonal therapy, psychodynamic therapy, problem solving, behavioral activation, and guided self-help.

The other key gap they pointed out relates to withdrawal.

Although the guideline does advise physicians to taper antidepressants to reduce risk of withdrawal, the editorialists suggested that this recommendation lacked sufficient emphasis, as it can be a particularly difficult period in the treatment process.

“Tapering of an antidepressant may need to be done over months or years, not weeks, and a patient may need to visit a compounding pharmacy to obtain doses of a second-generation antidepressant not marketed by drug manufacturers so that prescriptions can be tapered even more slowly,” they suggested.

Financial costs remain unclear

Beyond the above medical considerations, one other piece of the depression puzzle remains unsolved: cost.

In a simultaneously published rapid review, Andreea Dobrescu, MD, PhD, of Cochrane Austria, and colleagues evaluated the relative cost-effectiveness of first- and second-step treatment strategies.

For most comparisons, evidence was insufficient to reach a conclusion, although they suggested that CBT may be more cost effective at the 5-year mark.

“For most pharmacologic and nonpharmacologic interventions for major depressive disorder, evidence was missing or was insufficient to draw conclusions about the cost-effectiveness of first- or second-step treatments for MDD,” Dr. Dobrescu and colleagues wrote. “The strongest evidence (albeit still low certainty of evidence) was for the cost-effectiveness of CBT compared with SGA as a first-step treatment over a 5-year time horizon from the societal and health care sector perspectives. However, this evidence should also be interpreted cautiously considering it is based on a single study.”

When asked about the financial findings, Dr. Mire agreed that more data are needed, especially because CBT and SGA costs range widely. He suggested that cost, for each patient, should be considered in the personalized approach now highlighted by the new guidelines.

The guidelines and the Cochrane cost-effectiveness study were supported by the ACP. The guidelines' authors and other individuals quoted in this article reported no conflicts of interest.

The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
 

Olivier Le Moal/Getty Images

The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m².

Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m²).

In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.

In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.

“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.

“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”

As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.

Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.

Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.

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

The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
 

Olivier Le Moal/Getty Images

The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m².

Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m²).

In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.

In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.

“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.

“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”

As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.

Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.

Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.

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

The U.S. Food and Drug Administration has approved bexagliflozin (Brenzavvy, TheracosBio) for the treatment of adults with type 2 diabetes.
 

Olivier Le Moal/Getty Images

The once-daily 20-mg oral sodium-glucose cotransporter 2 (SGLT2) inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control for those with type 2 diabetes, but not type 1 diabetes. It can be used in adults with an estimated glomerular filtration rate (eGFR) > 30 mL/min per 1.73 m².

Approval was based on results from 23 clinical trials with more than 5,000 participants, including more than 300 patients with stage 3 kidney disease (eGFR < 60 and > 30 mL/min per 1.73 m²).

In the phase 3 studies, bexagliflozin significantly reduced hemoglobin A1c and fasting blood glucose at 24 weeks as monotherapy or as add-on to metformin and other glucose-lowering drugs and combinations. It also produced modest reductions in body weight and systolic blood pressure.

In the phase 3 Bexagliflozin Efficacy and Safety Trial (BEST) cardiovascular outcomes trial, the drug met its efficacy and safety objectives in patients at high cardiovascular risk. Noninferiority was demonstrated for the composite outcome of cardiovascular death, myocardial infarction, stroke, or unstable angina.

“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the Translational Research Center at Massachusetts General Hospital, Boston, in a press release from TheracosBio.

“Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”

As with other SGLT2 inhibitors, adverse events seen in the trials include ketoacidosis, lower limb amputation, volume depletion, urosepsis, pyelonephritis, Fournier’s gangrene, genital mycotic infections, and hypoglycemia when used with insulin or insulin secretagogues.

Bexagliflozin joins an already crowded field of SGLT2 inhibitors, some of which have been approved for additional cardiovascular and kidney indications.

Of interest, bexagliflozin was approved by the FDA for diabetes in cats in December 2022, as the first oral new animal drug to improve glycemic control in otherwise healthy cats with diabetes not previously treated with insulin.

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

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

Adding venetoclax to ibrutinib for chronic lymphocytic leukemia (CLL) improved rates of durable, treatment-free remission among 45 patients at the University of Texas MD Anderson Cancer Center, Houston.

Investigators led by Philip Thompson, MD, a hematologist/oncologist at the center, explained that CLL patients receiving ibrutinib, a Bruton’s kinase inhibitor, “rarely achieve complete remission with undetectable measurable residual disease,” so they stay on the costly treatment indefinitely or until disease progression or accumulating adverse events force a switch to venetoclax.

Using the two agents together, instead of consecutively, may allow strong responders to stop treatment altogether and suboptimal responders to have longer remissions, they said.

“We would not advocate prolonged Bruton’s kinase inhibitor use prior to starting venetoclax in treatment-naive patients, as the safety and efficacy of commencing venetoclax after a 3-month ibrutinib monotherapy phase has been repeatedly demonstrated,” the team said.

However, the investigators noted that their “study was not intended to directly answer the question of whether combination therapy is superior to the current paradigm of sequential monotherapy.” Randomized trials are looking into the matter. The study was published recently as a preprint on ResearchSquare.com and has not been peer reviewed.
 

Complete remission in over half

The 45 adult subjects had one or more high-risk features for CLL progression and had received at least 1 year of ibrutinib at 140-420 mg once daily, depending on tolerance. They had bone marrow detectable disease at study entry but did not meet criteria for progression. Median duration of ibrutinib at baseline was 32 months, and about half the subjects were on it as their initial therapy.

Venetoclax, a BCL2 inhibitor with a completely different mechanisms of action, was added to ibrutinib for up to 2 years, escalated up to a target dose of 400 mg once daily.

On intention-to-treat analysis, venetoclax add-on improved ibrutinib response to complete remission in 55% of patients; complete remission was defined as less than 1 CLL cell per 10,000 leukocytes in bone marrow on two consecutive occasions 6 months apart.

The rate of undetectable bone marrow disease was 57% after 1 year of combined treatment and 71% after venetoclax completion, at which point 23 patients with undetectable disease stopped ibrutinib along with venetoclax.

Five patients had disease progression at a median of 41 months after venetoclax initiation, one during combined therapy, three during ibrutinib maintenance afterward, and one with Richter transformation after complete remission and discontinuation of all treatment. No patient had died from CLL.

“There has so far been no significant difference noted in” time to residual disease re-emergence, the team said, based on whether or not patients continued ibrutinib after venetoclax add-on.

There was no significant difference in the rate of bone marrow clearance according to the presence or absence of TP53 abnormalities, complex karyotypes, or prior treatment status.

The most common grade 3/4 adverse event was neutropenia in 20% of patients. Nine patients developed nonmelanoma skin cancer during the trial; six were diagnosed with other solid tumors; three came down with grade 3 infections, and two developed myelodysplastic syndrome, both with a prior history of chemotherapy.

No one stopped venetoclax because of toxicity, but about a third of subjects required dose reductions, most often because of neutropenia.

The study was funded by AbbVie, which is commercializing venetoclax along with Genentech. Investigators disclosed ties to both companies and many others. Dr. Thompson disclosed ties to AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, Beigene, and Genentech.

A new scientific statement from the American Heart Association offers a standardized approach to rapidly evaluate patients with suspected transient ischemic attack (TIA), keeping in mind the challenges faced by rural centers with limited resources.

TIAs are “warning shots” of a future stroke and require emergency evaluation, Hardik Amin, MD, chair of the writing committee and medical stroke director, Yale New Haven (Conn.) Hospital, said in an AHA podcast.

A key aim of the scientific statement is to help clinicians properly risk-stratify patients with suspected TIA and determine which patients need to be admitted to the hospital and which patients might be safely discharged as long as proper and prompt follow-up has been arranged, Dr. Amin explained.

The statement, published online in the journal Stroke, addresses “how we can identify and be confident in diagnosing a TIA patient and what might suggest an alternative diagnosis,” he added.
 

Diagnostic challenge

It’s estimated that nearly one in five people who suffer a TIA will have a full-blown stroke within 3 months; close to half of these strokes will happen within 2 days.

The challenge with TIAs is that they can be tough to diagnose because many patients no longer have symptoms when they arrive at the emergency department. There is also no confirmatory test. Limited resources and access to stroke specialists in rural centers may exacerbate these challenges, the authors noted.

The statement pointed out that the F.A.S.T. acronym for stroke symptoms (Face drooping, Arm weakness, Speech difficulty, Time to call 911) can also be used to identify a TIA – even if the symptoms resolve.

The statement also provided guidance on how to tell the difference between a TIA and a TIA mimic.

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

A new scientific statement from the American Heart Association offers a standardized approach to rapidly evaluate patients with suspected transient ischemic attack (TIA), keeping in mind the challenges faced by rural centers with limited resources.

TIAs are “warning shots” of a future stroke and require emergency evaluation, Hardik Amin, MD, chair of the writing committee and medical stroke director, Yale New Haven (Conn.) Hospital, said in an AHA podcast.

A key aim of the scientific statement is to help clinicians properly risk-stratify patients with suspected TIA and determine which patients need to be admitted to the hospital and which patients might be safely discharged as long as proper and prompt follow-up has been arranged, Dr. Amin explained.

The statement, published online in the journal Stroke, addresses “how we can identify and be confident in diagnosing a TIA patient and what might suggest an alternative diagnosis,” he added.
 

Diagnostic challenge

It’s estimated that nearly one in five people who suffer a TIA will have a full-blown stroke within 3 months; close to half of these strokes will happen within 2 days.

The challenge with TIAs is that they can be tough to diagnose because many patients no longer have symptoms when they arrive at the emergency department. There is also no confirmatory test. Limited resources and access to stroke specialists in rural centers may exacerbate these challenges, the authors noted.

The statement pointed out that the F.A.S.T. acronym for stroke symptoms (Face drooping, Arm weakness, Speech difficulty, Time to call 911) can also be used to identify a TIA – even if the symptoms resolve.

The statement also provided guidance on how to tell the difference between a TIA and a TIA mimic.

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

A new scientific statement from the American Heart Association offers a standardized approach to rapidly evaluate patients with suspected transient ischemic attack (TIA), keeping in mind the challenges faced by rural centers with limited resources.

TIAs are “warning shots” of a future stroke and require emergency evaluation, Hardik Amin, MD, chair of the writing committee and medical stroke director, Yale New Haven (Conn.) Hospital, said in an AHA podcast.

A key aim of the scientific statement is to help clinicians properly risk-stratify patients with suspected TIA and determine which patients need to be admitted to the hospital and which patients might be safely discharged as long as proper and prompt follow-up has been arranged, Dr. Amin explained.

The statement, published online in the journal Stroke, addresses “how we can identify and be confident in diagnosing a TIA patient and what might suggest an alternative diagnosis,” he added.
 

Diagnostic challenge

It’s estimated that nearly one in five people who suffer a TIA will have a full-blown stroke within 3 months; close to half of these strokes will happen within 2 days.

The challenge with TIAs is that they can be tough to diagnose because many patients no longer have symptoms when they arrive at the emergency department. There is also no confirmatory test. Limited resources and access to stroke specialists in rural centers may exacerbate these challenges, the authors noted.

The statement pointed out that the F.A.S.T. acronym for stroke symptoms (Face drooping, Arm weakness, Speech difficulty, Time to call 911) can also be used to identify a TIA – even if the symptoms resolve.

The statement also provided guidance on how to tell the difference between a TIA and a TIA mimic.

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

Scientists have made big strides in the fight against cancer. A person’s risk of dying of cancer in the U.S. fell by 27% in the past 2 decades, thanks in large part to researchers who continue to uncover the complex details of how cancer works and to make advances in treatment. 

Now the emerging technology of 3D bioprinting – like 3D printing for the human body, using actual human cells – promises to speed up research by enabling scientists to develop 3D tumor models that better represent samples from patients.   

The impact could be “huge,” says Y. Shrike Zhang, PhD, an assistant professor of medicine at Harvard Medical School and associate bioengineer at Brigham and Women’s Hospital, both in Boston, who studies 3D bioprinting. “It is not the only technology that may allow modeling of tumors in vitro, but it certainly is one of the most capable.” 

Why does that matter? Because the 2D cell cultures that scientists often use now may not capture all the complexities of how cancer grows, spreads, and responds to treatment. It’s one reason why so few potential new cancer drugs – 3.4%, according to one estimate – can pass all clinical trials. Results may not carry over from the culture dish to the patient. 

Researchers say these 3D-printed blood vessels may treat certain dangerous health problems that affect your veins, arteries, or capillaries.

A 3D-bioprinted model, on the other hand, may be better at copying a tumor’s “microenvironment” – all the parts (cells, molecules, blood vessels) that surround a tumor. 

“The tumor microenvironment plays an integral role in defining how cancer progresses,” says Madhuri Dey, a PhD candidate and researcher at Penn State University. “In vitro 3D models are an attempt at reconstituting a [cancer] microenvironment, which sheds light on how tumors respond to chemo or immunotherapeutic treatments when they are present in a native-like microenvironment.”

Ms. Dey is the lead author of a study funded by the National Science Foundation in which breast cancer tumors were 3D-bioprinted and successfully treated. Unlike some previous 3D models of cancer cells, this model did a better job of imitating that microenvironment, she explains. 

So far, “3D bioprinting of cancer models has been limited to bioprinting of individual cancer cells laden in hydrogels,” she says. But she and her colleagues developed a technique called aspiration-assisted bioprinting that lets them control where blood vessels are located relative to the tumor. “This model lays the foundation for studying these nuances of cancer,” Ms. Dey says. 

“This is a quite cool work,” Dr. Zhang says of the Penn State study (which he was not involved in). “Vascularization is always a key component in [a] majority of the tumor types.” A model that incorporates blood vessels provides a “critical niche” to help tumor models reach their full potential in cancer research. 
 

A 3D printer for your body

Chances are you’ve heard of 3D printing and may even own (or know someone who owns) a 3D printer. The concept is like regular printing, but instead of spewing ink onto paper, a 3D printer releases layers of plastic or other materials, hundreds or thousands of times, to build an object from the ground up. 

Three-dimensional bioprinting works much the same way, except those layers are made of living cells to create biological structures like skin, vessels, organs, or bone. 

Bioprinting has been around since 1988. So far, it’s mainly used in research settings, such as in the field of regenerative medicine. Research is underway for ear reconstruction, nerve regeneration, and skin regeneration. The technology was also recently used to create eye tissue to help researchers study eye diseases. 

The technology’s potential for use in cancer research has yet to be fully realized, Ms. Dey says. But that may be changing. 

“The use of 3D-bioprinted tumor models is getting close to translations in cancer research,” says Dr. Zhang. “They are being increasingly adopted by the research field, and [the technology] has started to be explored by the pharma industry for use towards cancer drug development.” 

Because bioprinting can be automated, it could allow researchers to create high-quality, complex tumor models at scale, Dr. Zhang says.

Such 3D models also have the potential to replace or reduce the use of animals in tumor drug testing, Ms. Dey notes. They “are expected to provide a more accurate drug response, compared [with] animal models, as animal physiology does not match humans’.” 

The FDA Modernization Act 2.0, a new U.S. law eliminating the requirement that drugs be tested in animals before humans, has “further paved the way for such technologies in the drug development pipeline,” Dr. Zhang says.
 

What if we could build a custom tumor model for each patient? 

Possible uses for bioprinting go beyond the lab, Ms. Dey says. Imagine if we could customize 3D tumor models based on biopsies from individual patients. Doctors could test many treatments on these patient-specific models, letting them more accurately predict how each patient would respond to different therapies. This would help doctors decide which course of treatment is best. 

In Ms. Dey’s study, the 3D model was treated with chemotherapy and with immunotherapy, and it responded to both. This highlights the potential for such 3D models to reveal the body’s immune response and be used to screen therapies, she says. “We hope is that in the future, this technique can be adapted in the hospital, which would speed up the course of cancer treatment.”

To that end, she and her colleagues are now working with real breast cancer tumors removed from patients, re-creating them in the lab in 3D to use for chemo and immunotherapy screening.

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

Scientists have made big strides in the fight against cancer. A person’s risk of dying of cancer in the U.S. fell by 27% in the past 2 decades, thanks in large part to researchers who continue to uncover the complex details of how cancer works and to make advances in treatment. 

Now the emerging technology of 3D bioprinting – like 3D printing for the human body, using actual human cells – promises to speed up research by enabling scientists to develop 3D tumor models that better represent samples from patients.   

The impact could be “huge,” says Y. Shrike Zhang, PhD, an assistant professor of medicine at Harvard Medical School and associate bioengineer at Brigham and Women’s Hospital, both in Boston, who studies 3D bioprinting. “It is not the only technology that may allow modeling of tumors in vitro, but it certainly is one of the most capable.” 

Why does that matter? Because the 2D cell cultures that scientists often use now may not capture all the complexities of how cancer grows, spreads, and responds to treatment. It’s one reason why so few potential new cancer drugs – 3.4%, according to one estimate – can pass all clinical trials. Results may not carry over from the culture dish to the patient. 

Researchers say these 3D-printed blood vessels may treat certain dangerous health problems that affect your veins, arteries, or capillaries.

A 3D-bioprinted model, on the other hand, may be better at copying a tumor’s “microenvironment” – all the parts (cells, molecules, blood vessels) that surround a tumor. 

“The tumor microenvironment plays an integral role in defining how cancer progresses,” says Madhuri Dey, a PhD candidate and researcher at Penn State University. “In vitro 3D models are an attempt at reconstituting a [cancer] microenvironment, which sheds light on how tumors respond to chemo or immunotherapeutic treatments when they are present in a native-like microenvironment.”

Ms. Dey is the lead author of a study funded by the National Science Foundation in which breast cancer tumors were 3D-bioprinted and successfully treated. Unlike some previous 3D models of cancer cells, this model did a better job of imitating that microenvironment, she explains. 

So far, “3D bioprinting of cancer models has been limited to bioprinting of individual cancer cells laden in hydrogels,” she says. But she and her colleagues developed a technique called aspiration-assisted bioprinting that lets them control where blood vessels are located relative to the tumor. “This model lays the foundation for studying these nuances of cancer,” Ms. Dey says. 

“This is a quite cool work,” Dr. Zhang says of the Penn State study (which he was not involved in). “Vascularization is always a key component in [a] majority of the tumor types.” A model that incorporates blood vessels provides a “critical niche” to help tumor models reach their full potential in cancer research. 
 

A 3D printer for your body

Chances are you’ve heard of 3D printing and may even own (or know someone who owns) a 3D printer. The concept is like regular printing, but instead of spewing ink onto paper, a 3D printer releases layers of plastic or other materials, hundreds or thousands of times, to build an object from the ground up. 

Three-dimensional bioprinting works much the same way, except those layers are made of living cells to create biological structures like skin, vessels, organs, or bone. 

Bioprinting has been around since 1988. So far, it’s mainly used in research settings, such as in the field of regenerative medicine. Research is underway for ear reconstruction, nerve regeneration, and skin regeneration. The technology was also recently used to create eye tissue to help researchers study eye diseases. 

The technology’s potential for use in cancer research has yet to be fully realized, Ms. Dey says. But that may be changing. 

“The use of 3D-bioprinted tumor models is getting close to translations in cancer research,” says Dr. Zhang. “They are being increasingly adopted by the research field, and [the technology] has started to be explored by the pharma industry for use towards cancer drug development.” 

Because bioprinting can be automated, it could allow researchers to create high-quality, complex tumor models at scale, Dr. Zhang says.

Such 3D models also have the potential to replace or reduce the use of animals in tumor drug testing, Ms. Dey notes. They “are expected to provide a more accurate drug response, compared [with] animal models, as animal physiology does not match humans’.” 

The FDA Modernization Act 2.0, a new U.S. law eliminating the requirement that drugs be tested in animals before humans, has “further paved the way for such technologies in the drug development pipeline,” Dr. Zhang says.
 

What if we could build a custom tumor model for each patient? 

Possible uses for bioprinting go beyond the lab, Ms. Dey says. Imagine if we could customize 3D tumor models based on biopsies from individual patients. Doctors could test many treatments on these patient-specific models, letting them more accurately predict how each patient would respond to different therapies. This would help doctors decide which course of treatment is best. 

In Ms. Dey’s study, the 3D model was treated with chemotherapy and with immunotherapy, and it responded to both. This highlights the potential for such 3D models to reveal the body’s immune response and be used to screen therapies, she says. “We hope is that in the future, this technique can be adapted in the hospital, which would speed up the course of cancer treatment.”

To that end, she and her colleagues are now working with real breast cancer tumors removed from patients, re-creating them in the lab in 3D to use for chemo and immunotherapy screening.

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

Scientists have made big strides in the fight against cancer. A person’s risk of dying of cancer in the U.S. fell by 27% in the past 2 decades, thanks in large part to researchers who continue to uncover the complex details of how cancer works and to make advances in treatment. 

Now the emerging technology of 3D bioprinting – like 3D printing for the human body, using actual human cells – promises to speed up research by enabling scientists to develop 3D tumor models that better represent samples from patients.   

The impact could be “huge,” says Y. Shrike Zhang, PhD, an assistant professor of medicine at Harvard Medical School and associate bioengineer at Brigham and Women’s Hospital, both in Boston, who studies 3D bioprinting. “It is not the only technology that may allow modeling of tumors in vitro, but it certainly is one of the most capable.” 

Why does that matter? Because the 2D cell cultures that scientists often use now may not capture all the complexities of how cancer grows, spreads, and responds to treatment. It’s one reason why so few potential new cancer drugs – 3.4%, according to one estimate – can pass all clinical trials. Results may not carry over from the culture dish to the patient. 

Researchers say these 3D-printed blood vessels may treat certain dangerous health problems that affect your veins, arteries, or capillaries.

A 3D-bioprinted model, on the other hand, may be better at copying a tumor’s “microenvironment” – all the parts (cells, molecules, blood vessels) that surround a tumor. 

“The tumor microenvironment plays an integral role in defining how cancer progresses,” says Madhuri Dey, a PhD candidate and researcher at Penn State University. “In vitro 3D models are an attempt at reconstituting a [cancer] microenvironment, which sheds light on how tumors respond to chemo or immunotherapeutic treatments when they are present in a native-like microenvironment.”

Ms. Dey is the lead author of a study funded by the National Science Foundation in which breast cancer tumors were 3D-bioprinted and successfully treated. Unlike some previous 3D models of cancer cells, this model did a better job of imitating that microenvironment, she explains. 

So far, “3D bioprinting of cancer models has been limited to bioprinting of individual cancer cells laden in hydrogels,” she says. But she and her colleagues developed a technique called aspiration-assisted bioprinting that lets them control where blood vessels are located relative to the tumor. “This model lays the foundation for studying these nuances of cancer,” Ms. Dey says. 

“This is a quite cool work,” Dr. Zhang says of the Penn State study (which he was not involved in). “Vascularization is always a key component in [a] majority of the tumor types.” A model that incorporates blood vessels provides a “critical niche” to help tumor models reach their full potential in cancer research. 
 

A 3D printer for your body

Chances are you’ve heard of 3D printing and may even own (or know someone who owns) a 3D printer. The concept is like regular printing, but instead of spewing ink onto paper, a 3D printer releases layers of plastic or other materials, hundreds or thousands of times, to build an object from the ground up. 

Three-dimensional bioprinting works much the same way, except those layers are made of living cells to create biological structures like skin, vessels, organs, or bone. 

Bioprinting has been around since 1988. So far, it’s mainly used in research settings, such as in the field of regenerative medicine. Research is underway for ear reconstruction, nerve regeneration, and skin regeneration. The technology was also recently used to create eye tissue to help researchers study eye diseases. 

The technology’s potential for use in cancer research has yet to be fully realized, Ms. Dey says. But that may be changing. 

“The use of 3D-bioprinted tumor models is getting close to translations in cancer research,” says Dr. Zhang. “They are being increasingly adopted by the research field, and [the technology] has started to be explored by the pharma industry for use towards cancer drug development.” 

Because bioprinting can be automated, it could allow researchers to create high-quality, complex tumor models at scale, Dr. Zhang says.

Such 3D models also have the potential to replace or reduce the use of animals in tumor drug testing, Ms. Dey notes. They “are expected to provide a more accurate drug response, compared [with] animal models, as animal physiology does not match humans’.” 

The FDA Modernization Act 2.0, a new U.S. law eliminating the requirement that drugs be tested in animals before humans, has “further paved the way for such technologies in the drug development pipeline,” Dr. Zhang says.
 

What if we could build a custom tumor model for each patient? 

Possible uses for bioprinting go beyond the lab, Ms. Dey says. Imagine if we could customize 3D tumor models based on biopsies from individual patients. Doctors could test many treatments on these patient-specific models, letting them more accurately predict how each patient would respond to different therapies. This would help doctors decide which course of treatment is best. 

In Ms. Dey’s study, the 3D model was treated with chemotherapy and with immunotherapy, and it responded to both. This highlights the potential for such 3D models to reveal the body’s immune response and be used to screen therapies, she says. “We hope is that in the future, this technique can be adapted in the hospital, which would speed up the course of cancer treatment.”

To that end, she and her colleagues are now working with real breast cancer tumors removed from patients, re-creating them in the lab in 3D to use for chemo and immunotherapy screening.

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

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

Cancer dietitian Lisa Cianciotta often finds herself sitting across from a patient who suddenly fishes a bottle of antioxidant supplements from their bag and says, “My friend told me this works really well,” or “I read on the Internet that this is supposed to be really good for cancer.” 

Although taking an antioxidant pill sounds harmless, Ms. Cianciotta, a clinical dietitian who works with cancer patients at New York–Presbyterian Hospital, knows well that this popular dietary supplement can interfere with a patient’s radiation or chemotherapy.

But many patients with cancer believe these over-the-counter vitamins, minerals, or herbal remedies will help them, and most use at least one dietary supplement alongside their cancer treatment.

And that leaves Ms. Cianciotta with a delicate conversation ahead of her. 

Drug-supplement interactions are complex, often varying by supplement, cancer, and treatment type, and can do more harm than good. Popular dietary supplements may, for instance, cancel the effects of a cancer treatment, making it less effective, or increase serious side effects, such as liver toxicity. But in other cases, supplementation, such as vitamin D for patients who lack the vitamin, may be beneficial, Ms. Cianciotta said. 

These drug-supplement interactions can be hard to pinpoint, given that more than two-thirds of doctors don’t know their patients are using supplements.

Here’s what patients need to know about the potential risks of supplement use during treatment, and how oncologists can address this thorny, often poorly understood topic with patients.
 

The complex drug-supplement landscape

The list of dietary supplements and how they can interact with different treatments and cancer types is long and nuanced. 

But certain supplements appear to affect cancer treatments regardless of other things and should be avoided. Any supplement that strongly alters the body’s levels of the protein cytochromes P450 is one example. This group of enzymes plays a key role in metabolizing drugs, including chemotherapy and immunotherapy agents. 

Certain supplements – most notably St. John’s wort extract – may decrease or increase the activity of cytochrome P450, which can then  affect the concentrations of anticancer drugs in the blood, said William Figg, PharmD, an associate director of the Center for Cancer Research at the National Cancer Institute in Bethesda, Md. Studies show, for instance, that this common herbal supplement can increase the activity of cytochrome P450, resulting in lower levels of cancer drugs.

Outside of drug metabolism, patients with hormone-related cancers, such as breast and prostate cancers, should steer clear of dietary supplements that can alter levels of testosterone or estrogen, Dr. Figg said. The evergreen shrub ashwagandha, for example, is marketed to reduce stress and fatigue, but can also increase testosterone levels – a potential problem for those with prostate cancer receiving androgen deprivation therapy, which lowers testosterone levels. 

Many oncologists counsel patients against using antioxidant-based dietary supplements – particularly turmeric and green tea extract – while they have radiation therapy and certain chemotherapies. These therapies work by creating an abundance of highly reactive molecules called free radicals in tumor cells, which increase stress within these cells, ultimately killing them off. Antioxidants, in theory, can neutralize this effect, said Skyler Johnson, MD, a radiation oncologist at Huntsman Cancer Institute at the University of Utah, Salt Lake City.  Some studies suggest that antioxidant supplements may lessen the effects of radiation and chemotherapy, although the evidence is mixed.

Some dietary supplements, including high-dose green tea extract and vitamin A, can cause kidney or liver toxicity, and “many cancer patients already have compromised kidney or liver function,” said Jun J. Mao, MD, chief of integrative medicine at Memorial Sloan Kettering Cancer Center in New York. Even herbs that don’t interfere with how well a cancer drug works, such as stevia, can increase treatment-related side effects, such as nausea and vomiting. 

Another potential problem with dietary supplements: It’s nearly impossible to know exactly what’s in them. For instance, just last year, the Food and Drug Administration sent nearly 50 warning letters to companies marketing dietary supplements. The issue is that federal regulations governing production are less strict for supplements than for medications. As a result, some supplements contain ingredients not listed on the label. 

One historical example was the supplement PC-SPES, a mix of eight herbs, marketed to men with prostate cancer. The supplement was recalled in 2002 after certain batches were found to contain traces of prescription drugs, including diethylstilbestrol, ethinyl estradiol, warfarin, and alprazolam.

To further complicate matters, some dietary supplements can be helpful. Most patients with cancer “are malnourished and missing out on nutrients they could be getting from food,” said Ms. Cianciotta.

Patients are tested routinely for vitamin deficiencies and receive supplements as needed, she said. Vitamin D and folic acid are two of the most common deficiencies in this patient population. Vitamin D supplementation can improve outcomes in patients who have received a stem cell transplant by aiding engraftment and rebuilding the immune system, while folic acid supplementation can help to raise low red blood cell counts and hemoglobin levels. 

Although she rarely sees vitamin toxicity, Ms. Cianciotta stressed that more is not always better and supplement use, even when it seems safe or warranted due to a deficiency, should be taken under supervision, and monitored carefully by the patient’s care team. 
 

Bringing supplement use into the light

Too often, providers are unaware of a patient’s supplement use. 

A core reason: Dietary supplements are often touted as natural, which many patients equate with safety, said Samantha Heller, a senior clinical nutritionist at New York (N.Y.) University Langone Health. 

That means patients may not know a supplement can act like a drug and interfere with their cancer treatment, and thus may not see the importance of telling their doctors.

Still, the promise of herbs, vitamins, and minerals can be alluring, and there are many reasons patients decide to partake. One major appeal: Dietary supplements can help some patients feel empowered.

“Cancer is a disease that takes away a lot of control from the individual. Taking supplements or herbs is a way to regain some sense of control,” said Dr. Mao. 

The phenomenon can also be cultural, he said. Some people grow up taking herbs and supplements to stay healthy or combat health woes.

Pressure or advice from family or friends who may think they are helping a loved one with their dietary recommendations may play a role as well. Friends and family “cannot prescribe chemo, but they can buy herbs and supplements,” Dr. Mao said. 

Patients seeking greater control over their health or who feel high levels of anxiety may be more likely to take suggestions from friends and family or more likely to believe false or misleading claims about the efficacy or safety of supplements, explained  medical oncologist William Dahut, MD, chief scientific officer for the American Cancer Society. 

Plus, social media often amplifies and normalizes this misinformation, noted Dr. Johnson. In a 2021 study published in the Journal of the National Cancer Institute, he and colleagues found that one-third of the most popular articles on cancer treatment posted to social media in 2018 and 2019 contained false, inaccurate, or misleading information that was often harmful. 

Some of the false claims centered on unproven, potentially unsafe herbal remedies, according to Dr. Johnson. These included “lung cancer can be cured with cannabis oil” and “golden berries cure and prevent cancer.” 

Given exaggerated claims of “cures,” some patients may keep their supplement use under the radar out of fear they will be judged or criticized. 

“Clinicians should avoid making patients feel judged or telling people not to go online to do their own research,” Dr. Johnson said.

Guiding patients, instead, to accurate sources of online information may be one way to help patients feel empowered, he said. Cancer.gov and the Memorial Sloan Kettering Cancer Center’s About Herbs database provide accessible and accurate information on dietary supplements and cancer treatment for both health care professionals and patients, he noted. 

If a particular supplement is not safe during treatment, providers should be able to explain why, said  Ms. Cianciotta. In a recent study, 80% of health care providers surveyed believed that interactions between herbals and medications could be problematic, but only 15% could explain why. 

“Being able to explain why we are discouraging a particular supplement right now tends to be much better received than just telling a patient not to take something, because it is bad,” she said. 

Another key is listening closely to patients to understand why they may be taking a particular supplement. Does the patient feel out of control? Is nausea a problem? 

“Allowing patients to tell you why they are using a particular supplement will often reveal unmet needs or psychosocial challenges,” Dr. Mao said. This information can allow providers to suggest an evidence-based alternative, such as mindfulness meditation or acupuncture, to manage stress.

And if a patient has received a dietary supplement from well-meaning family and friends?

“Simply telling a patient that a given supplement is useless or harmful could create family tension,” said  Dr. Mao. 

Instead, he recommends reframing the issue. 

“We want to have a better understanding of how patients are tolerating chemo or immunotherapy before throwing other things on top of it. Let them know that now may just not be the right time to add a supplement to the mix,” Dr. Mao said. 

The bottom line: “Patients want to play an active role in their own care, and we want to help them do that in a safe way,” he said. 

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

ABSTRACT

Objective: Promoting a culture of safety is a critical component of improving health care quality. Recognizing staff who stop the line for safety can positively impact the growth of a culture of safety. The purpose of this initiative was to demonstrate to staff the importance of speaking up for safety and being acknowledged for doing so.

Methods: Following a review of the literature on safety awards programs and their role in promoting a culture of safety in health care covering the period 2017 to 2020, a formal process was developed and implemented to disseminate safety awards to employees.

Results: During the initial 18 months of the initiative, a total of 59 awards were presented. The awards were well received by the recipients and other staff members. Within this period, adjustments were made to enhance the scope and reach of the program.

Conclusion: Recognizing staff behaviors that support a culture of safety is important for improving health care quality and employee engagement. Future research should focus on a formal evaluation of the impact of safety awards programs on patient safety outcomes.

Keywords: patient safety, culture of safety, incident reporting, near miss.

A key aspect of improving health care quality is promoting and sustaining a culture of safety in the workplace. Improving the quality of health care services and systems involves making informed choices regarding the types of strategies to implement.¹ An essential aspect of supporting a safety culture is safety-event reporting. To approach the goal of zero harm, all safety events, whether they result in actual harm or are considered near misses, need to be reported. Near-miss events are errors that occur while care is being provided but are detected and corrected before harm reaches the patient.^1-3 Near-miss reporting plays a critical role in helping to identify and correct weaknesses in health care delivery systems and processes.⁴ However, evidence shows that there are a multitude of barriers to the reporting of near-miss events, such as fear of punitive actions, additional workload, unsupportive work environments, a culture with poor psychological safety, knowledge deficit, and lack of recognition of staff who do report near misses.^4-11

According to The Joint Commission (TJC), acknowledging health care team members who recognize and report unsafe conditions that provide insight for improving patient safety is a key method for promoting the reporting of near-miss events.⁶ As a result, some health care organizations and patient safety agencies have started to institute some form of recognition for their employees in the realm of safety.^8-10 The Pennsylvania Patient Safety Authority offers exceptional guidance for creating a safety awards program to promote a culture of safety.¹² Furthermore, TJC supports recognizing individuals and health care teams who identify and report near misses, or who have suggestions for initiatives to promote patient safety, with “good catch” awards. Individuals or teams working to promote and sustain a culture of safety should be recognized for their efforts. Acknowledging “good catches” to reward the identification, communication, and resolution of safety issues is an effective strategy for improving patient safety and health care quality.^6,8

This quality improvement (QI) initiative was undertaken to demonstrate to staff that, in building an organizational culture of safety, it is important that staff be encouraged to speak up for safety and be acknowledged for doing so. If health care organizations want staff to be motivated to report near misses and improve safety and health care quality, the culture needs to shift from focusing on blame to incentivizing individuals and teams to speak up when they have concerns.^8-10 Although deciding which safety actions are worthy of recognition can be challenging, recognizing all safe acts, regardless of how big or small they are perceived to be, is important. This QI initiative aimed to establish a tiered approach to recognize staff members for various categories of safety acts.

METHODS

A review of the literature from January 2017 to May 2020 for peer-reviewed publications regarding how other organizations implemented safety award programs to promote a culture of safety resulted in a dearth of evidence. This prompted us at the Veterans Affairs Connecticut Healthcare System to develop and implement a formal program to disseminate safety awards to employees.

Program Launch and Promotion

In 2020, our institution embarked on a journey to high reliability with the goal of approaching zero harm. As part of efforts to promote a culture of safety, the hospital’s High Reliability Organization (HRO) team worked to develop a safety awards recognition program. Prior to the launch, the hospital’s patient safety committee recognized staff members through the medical center safety event reporting system (the Joint Patient Safety Reporting system [JPSR]) or through direct communication with staff members on safety actions they were engaged in. JPSR is the Veterans Health Administration National Center for Patient Safety incident reporting system for reporting, tracking, and trending of patient incidents in a national database. The award consisted of a certificate presented by the patient safety committee chairpersons to the employee in front of their peers in their respective work area. Hospital leadership was not involved in the safety awards recognition program at that time. No nomination process existed prior to our QI launch.

Once the QI initiative was launched and marketed heavily at staff meetings, we started to receive nominations for actions that were truly exceptional, while many others were submitted for behaviors that were within the day-to-day scope of practice of the staff member. For those early nominations that did not meet criteria for an award, we thanked staff for their submissions with a gentle statement that their nomination did not meet the criteria for an award. After following this practice for a few weeks, we became concerned that if we did not acknowledge the staff who came forward to request recognition for their routine work that supported safety, we could risk losing their engagement in a culture of safety. As such, we decided to create 3 levels of awards to recognize behaviors that went above and beyond while also acknowledging staff for actions within their scope of practice. Additionally, hospital leadership wanted to ensure that all staff recognize that their safety efforts are valued by leadership and that that sense of value will hopefully contribute to a culture of safety over time.

Initially, the single award system was called the “Good Catch Award” to acknowledge staff who go above and beyond to speak up and take action when they have safety concerns. This particular recognition includes a certificate, an encased baseball card that has been personalized by including the staff member’s picture and safety event identified, a stress-release baseball, and a stick of Bazooka gum (similar to what used to come in baseball cards packs). The award is presented to employees in their work area by the HRO and patient safety teams and includes representatives from the executive leadership team (ELT). The safety event identified is described by an ELT member, and all items are presented to the employee. Participation by the leadership team communicates how much the work being done to promote a culture of safety and advance quality health care is appreciated. This action also encourages others in the organization to identify and report safety concerns.¹³

With the rollout of the QI initiative, the volume of nominations submitted quickly increased (eg, approximately 1 every 2 months before to 3 per month following implementation). Frequently, nominations were for actions believed to be within the scope of the employee’s responsibilities. Our institution’s leadership team quickly recognized that, as an organization, not diminishing the importance of the “Good Catch Award” was important. However, the leadership team also wanted to encourage nominations from employees that involved safety issues that were part of the employee’s scope of responsibilities. As a result, 2 additional and equally notable award tiers were established, with specific criteria created for each.¹⁴ The addition of the other awards was instrumental in getting the leadership team to feel confident that all staff were being recognized for their commitment to patient safety.

The original Good Catch Award was labelled as a Level 1 award. The Level 2 safety recognition award, named the HRO Safety Champion Award, is given to employees who stop the line for a safety concern within their scope of practice and also participate as part of a team to investigate and improve processes to avoid recurring safety concerns in the future. For the Level Two award, a certificate is presented to an employee by the hospital’s HRO lead, HRO physician champion, patient safety manager, immediate supervisor, and peers. With the Level 3 award, the Culture of Safety Appreciation Award, individuals are recognized for addressing safety concerns within their assigned scope of responsibilities. Recognition is bestowed by an email of appreciation sent to the employee, acknowledging their commitment to promoting a culture of safety and quality health care. The recipient’s direct supervisor and other hospital leaders are copied on the message.¹⁴ See Table 1 for a comparison of awards.

Our institution’s HRO and patient safety teams utilized many additional venues to disseminate information regarding awardees and their actions. These included our monthly HRO newsletter, monthly safety forums, and biweekly Team Connecticut Healthcare system-wide huddles.

Nomination Process

Awards nominations are submitted via the hospital intranet homepage, where there is an “HRO Safety Award Nomination” icon. Once a staff member clicks the icon, a template opens asking for information, such as the reason for the nomination submission, and then walks them through the template using the CAR (C-context, A-actions, and R-results)¹⁵ format for describing the situation, identifying actions taken, and specifying the outcome of the action. Emails with award nominations can also be sent to the HRO lead, HRO champion, or Patient Safety Committee co-chairs. Calls for nominations are made at several venues attended by employees as well as supervisors. These include monthly safety forums, biweekly Team Connecticut Healthcare system-wide huddles, supervisory staff meetings, department and unit-based staff meetings, and many other formal and informal settings. This QI initiative has allowed us to capture potential awardees through several avenues, including self-nominations. All nominations are reviewed by a safety awards committee. Each committee member ranks the nomination as a Level 1, 2, or 3 award. For nominations where conflicting scores are obtained, the committee discusses the nomination together to resolve discrepancies.

Needed Resources

Material resources required for this QI initiative include certificate paper, plastic baseball card sleeves, stress-release baseballs, and Bazooka gum. The largest resource investment was the time needed to support the initiative. This included the time spent scheduling the Level 1 and 2 award presentations with staff and leadership. Time was also required to put the individual award packages together, which included printing the paper certificates, obtaining awardee pictures, placing them with their safety stories in a plastic baseball card sleeve, and arranging for the hospital photographer to take pictures of the awardees with their peers and leaders.

RESULTS

Prior to this QI initiative launch, 14 awards were given out over the preceding 2-year period. During the initial 18 months of the initiative (December 2020 to June 2022), 59 awards were presented (Level 1, n = 26; Level 2, n = 22; and Level 3, n = 11). Looking further into the Level 1 awards presented, 25 awardees worked in clinical roles and 1 in a nonclinical position (Table 2). The awardees represented multidisciplinary areas, including medical/surgical (med/surg) inpatient units, anesthesia, operating room, pharmacy, mental health clinics, surgical intensive care, specialty care clinics, and nutrition and food services. With the Level 2 awards, 18 clinical staff and 4 nonclinical staff received awards from the areas of med/surg inpatient, outpatient surgical suites, the medical center director’s office, radiology, pharmacy, primary care, facilities management, environmental management, infection prevention, and emergency services. All Level 3 awardees were from clinical areas, including primary care, hospital education, sterile processing, pharmacies, operating rooms, and med/surg inpatient units.

With the inception of this QI initiative, our organization has begun to see trends reflecting increased reporting of both actual and close-call events in JPSR (Figure 1).

With the inclusion of information regarding awardees and their actions in monthly safety forums, attendance at these forums has increased from an average of 64 attendees per month in 2021 to an average of 131 attendees per month in 2022 (Figure 2).

Finally, our organization’s annual All-Employee Survey results have shown incremental increases in staff reporting feeling psychologically safe and not fearing reprisal (Figure 3). It is important to note that there may be other contributing factors to these incremental changes.

Stories From the 3 Award Categories

Level 1 – Good Catch Award. M.S. was assigned as a continuous safety monitor, or “sitter,” on one of the med/surg inpatient units. M.S. arrived at the bedside and asked for a report on the patient at a change in shift. The report stated that the patient was sleeping and had not moved in a while. M.S. set about to perform the functions of a sitter and did her usual tasks in cleaning and tidying the room for the patient for breakfast and taking care of all items in the room, in general. M.S. introduced herself to the patient, who she thought might wake up because of her speaking to him. She thought the patient was in an odd position, and knowing that a patient should be a little further up in the bed, she tried with touch to awaken him to adjust his position. M.S. found that the patient was rather chilly to the touch and immediately became concerned. She continued to attempt to rouse the patient. M.S. called for the nurse and began to adjust the patient’s position. M.S. insisted that the patient was cold and “something was wrong.” A set of vitals was taken and a rapid response team code was called. The patient was immediately transferred to the intensive care unit to receive a higher level of care. If not for the diligence and caring attitude of M.S., this patient may have had a very poor outcome.

Reason for criteria being met: The scope of practice of a sitter is to be present in a patient’s room to monitor for falls and overall safety. This employee noticed that the patient was not responsive to verbal or tactile stimuli. Her immediate reporting of her concern to the nurse resulted in prompt intervention. If she had let the patient be, the patient could have died. The staff member went above and beyond by speaking up and taking action when she had a patient safety concern.

Level 2 – HRO Safety Champion Award. A patient presented to an outpatient clinic for monoclonal antibody (mAb) therapy for a COVID-19 infection; the treatment has been scheduled by the patient’s primary care provider. At that time, outpatient mAb therapy was the recommended care option for patients stable enough to receive treatment in this setting, but it is contraindicated in patients who are too unstable to receive mAb therapy in an outpatient setting, such as those with increased oxygen demands. R.L., a staff nurse, assessed the patient on arrival and found that his vital signs were stable, except for a slightly elevated respiratory rate. Upon questioning, the patient reported that he had increased his oxygen use at home from 2 to 4 L via a nasal cannula. R.L. assessed that the patient was too high-risk for outpatient mAb therapy and had the patient checked into the emergency department (ED) to receive a full diagnostic workup and evaluation by Dr. W., an ED provider. The patient required admission to the hospital for a higher level of care in an inpatient unit because of severe COVID-19 infection. Within 48 hours of admission, the patient’s condition further declined, requiring an upgrade to the medical intensive care unit with progressive interventions. Owing to the clinical assessment skills and prompt action of R.L., the patient was admitted to the hospital instead of receiving treatment in a suboptimal care setting and returning home. Had the patient gone home, his rapid decline could have had serious consequences.

Reason for criteria being met: On a cursory look, the patient may have passed as someone sufficiently stable to undergo outpatient treatment. However, the nurse stopped the line, paid close attention, and picked up on an abnormal vital sign and the projected consequences. The nurse brought the patient to a higher level of care in the ED so that he could get the attention he needed. If this patient was given mAb therapy in the outpatient setting, he would have been discharged and become sicker with the COVID-19 illness. As a result of this incident, R.L. is working with the outpatient clinic and ED staff to enahance triage and evaluation of patients referred for outpatient therapy for COVID-19 infections to prevent a similar event from recurring.

Level 3 – Culture of Safety Appreciation Award. While C.C. was reviewing the hazardous item competencies of the acute psychiatric inpatient staff, it was learned that staff were sniffing patients’ personal items to see if they were “safe” and free from alcohol. This is a potentially dangerous practice, and if fentanyl is present, it can be life-threatening. All patients admitted to acute inpatient psychiatry have all their clothing and personal items checked for hazardous items—pockets are emptied, soles of shoes are lifted, and so on. Staff wear personal protective equipment during this process to mitigate any powders or other harmful substances being inhaled or coming in contact with their skin or clothes. The gloves can be punctured if needles are found in the patient’s belongings. C.C. not only educated the staff on the dangers of sniffing for alcohol during hazardous-item checks, but also looked for further potential safety concerns. An additional identified risk was for needle sticks when such items were found in a patient’s belongings. C.C.’s recommendations included best practices to allow only unopened personal items and have available hospital-issued products as needed. C.C. remembered having a conversation with an employee from the psychiatric emergency room regarding the purchase of puncture-proof gloves to mitigate puncture sticks. C.C. recommended that the same gloves be used by staff on the acute inpatient psychiatry unit during searches for hazardous items.

Reason for criteria being met: The employee works in the hospital education department. It is within her scope of responsibilities to provide ongoing education to staff in order to address potential safety concerns.

DISCUSSION

This QI initiative was undertaken to demonstrate to staff that, in building an organizational culture of safety and advancing quality health care, it is important that staff be encouraged to speak up for safety and be acknowledged for doing so. As part of efforts to continuously build on a safety-first culture, transparency and celebration of successes were demonstrated. This QI initiative demonstrated that a diverse and wide range of employees were reached, from clinical to nonclinical staff, and frontline to supervisory staff, as all were included in the recognition process. While many award nominations were received through the submission of safety concerns to the high-reliability team and patient safety office, several came directly from staff who wanted to recognize their peers for their work, supporting a culture of safety. This showed that staff felt that taking the time to submit a write-up to recognize a peer was an important task. Achieving zero harm for patients and staff alike is a top priority for our institution and guides all decisions, which reinforces that everyone has a responsibility to ensure that safety is always the first consideration. A culture of safety is enhanced by staff recognition. This QI initiative also showed that staff felt valued when they were acknowledged, regardless of the level of recognition they received. The theme of feeling valued came from unsolicited feedback. For example, some direct comments from awardees are presented in the Box.

In addition to endorsing the importance of safe practices to staff, safety award programs can identify gaps in existing standard procedures that can be updated quickly and shared broadly across a health care organization. The authors observed that the existence of the award program gives staff permission to use their voice to speak up when they have questions or concerns related to safety and to proactively engage in safety practices; a cultural shift of this kind informs safety practices and procedures and contributes to a more inspiring workplace. Staff at our organization who have received any of the safety awards, and those who are aware of these awards, have embraced the program readily. At the time of submission of this manuscript, there was a relative paucity of published literature on the details, performance, and impact of such programs. This initiative aims to share a road map highlighting the various dimensions of staff recognition and how the program supports our health care system in fostering a strong, sustainable culture of safety and health care quality. A next step is to formally assess the impact of the awards program on our culture of safety and quality using a psychometrically sound measurement tool, as recommended by TJC,¹⁶ such as the Hospital Survey on Patient Safety Culture.^17,18

CONCLUSION

A health care organization safety awards program is a strategy for building and sustaining a culture of safety. This QI initiative may be valuable to other organizations in the process of establishing a safety awards program of their own. Future research should focus on a formal evaluation of the impact of safety awards programs on patient safety outcomes.

Corresponding author: John S. Murray, PhD, MPH, MSGH, RN, FAAN, 20 Chapel Street, Unit A502, Brookline, MA 02446; [email protected]

Disclosures: None reported.

ABSTRACT

Objective: Promoting a culture of safety is a critical component of improving health care quality. Recognizing staff who stop the line for safety can positively impact the growth of a culture of safety. The purpose of this initiative was to demonstrate to staff the importance of speaking up for safety and being acknowledged for doing so.

Methods: Following a review of the literature on safety awards programs and their role in promoting a culture of safety in health care covering the period 2017 to 2020, a formal process was developed and implemented to disseminate safety awards to employees.

Results: During the initial 18 months of the initiative, a total of 59 awards were presented. The awards were well received by the recipients and other staff members. Within this period, adjustments were made to enhance the scope and reach of the program.

Conclusion: Recognizing staff behaviors that support a culture of safety is important for improving health care quality and employee engagement. Future research should focus on a formal evaluation of the impact of safety awards programs on patient safety outcomes.

Keywords: patient safety, culture of safety, incident reporting, near miss.

A key aspect of improving health care quality is promoting and sustaining a culture of safety in the workplace. Improving the quality of health care services and systems involves making informed choices regarding the types of strategies to implement.¹ An essential aspect of supporting a safety culture is safety-event reporting. To approach the goal of zero harm, all safety events, whether they result in actual harm or are considered near misses, need to be reported. Near-miss events are errors that occur while care is being provided but are detected and corrected before harm reaches the patient.^1-3 Near-miss reporting plays a critical role in helping to identify and correct weaknesses in health care delivery systems and processes.⁴ However, evidence shows that there are a multitude of barriers to the reporting of near-miss events, such as fear of punitive actions, additional workload, unsupportive work environments, a culture with poor psychological safety, knowledge deficit, and lack of recognition of staff who do report near misses.^4-11

According to The Joint Commission (TJC), acknowledging health care team members who recognize and report unsafe conditions that provide insight for improving patient safety is a key method for promoting the reporting of near-miss events.⁶ As a result, some health care organizations and patient safety agencies have started to institute some form of recognition for their employees in the realm of safety.^8-10 The Pennsylvania Patient Safety Authority offers exceptional guidance for creating a safety awards program to promote a culture of safety.¹² Furthermore, TJC supports recognizing individuals and health care teams who identify and report near misses, or who have suggestions for initiatives to promote patient safety, with “good catch” awards. Individuals or teams working to promote and sustain a culture of safety should be recognized for their efforts. Acknowledging “good catches” to reward the identification, communication, and resolution of safety issues is an effective strategy for improving patient safety and health care quality.^6,8

This quality improvement (QI) initiative was undertaken to demonstrate to staff that, in building an organizational culture of safety, it is important that staff be encouraged to speak up for safety and be acknowledged for doing so. If health care organizations want staff to be motivated to report near misses and improve safety and health care quality, the culture needs to shift from focusing on blame to incentivizing individuals and teams to speak up when they have concerns.^8-10 Although deciding which safety actions are worthy of recognition can be challenging, recognizing all safe acts, regardless of how big or small they are perceived to be, is important. This QI initiative aimed to establish a tiered approach to recognize staff members for various categories of safety acts.

METHODS

A review of the literature from January 2017 to May 2020 for peer-reviewed publications regarding how other organizations implemented safety award programs to promote a culture of safety resulted in a dearth of evidence. This prompted us at the Veterans Affairs Connecticut Healthcare System to develop and implement a formal program to disseminate safety awards to employees.

Program Launch and Promotion

In 2020, our institution embarked on a journey to high reliability with the goal of approaching zero harm. As part of efforts to promote a culture of safety, the hospital’s High Reliability Organization (HRO) team worked to develop a safety awards recognition program. Prior to the launch, the hospital’s patient safety committee recognized staff members through the medical center safety event reporting system (the Joint Patient Safety Reporting system [JPSR]) or through direct communication with staff members on safety actions they were engaged in. JPSR is the Veterans Health Administration National Center for Patient Safety incident reporting system for reporting, tracking, and trending of patient incidents in a national database. The award consisted of a certificate presented by the patient safety committee chairpersons to the employee in front of their peers in their respective work area. Hospital leadership was not involved in the safety awards recognition program at that time. No nomination process existed prior to our QI launch.

Once the QI initiative was launched and marketed heavily at staff meetings, we started to receive nominations for actions that were truly exceptional, while many others were submitted for behaviors that were within the day-to-day scope of practice of the staff member. For those early nominations that did not meet criteria for an award, we thanked staff for their submissions with a gentle statement that their nomination did not meet the criteria for an award. After following this practice for a few weeks, we became concerned that if we did not acknowledge the staff who came forward to request recognition for their routine work that supported safety, we could risk losing their engagement in a culture of safety. As such, we decided to create 3 levels of awards to recognize behaviors that went above and beyond while also acknowledging staff for actions within their scope of practice. Additionally, hospital leadership wanted to ensure that all staff recognize that their safety efforts are valued by leadership and that that sense of value will hopefully contribute to a culture of safety over time.

Initially, the single award system was called the “Good Catch Award” to acknowledge staff who go above and beyond to speak up and take action when they have safety concerns. This particular recognition includes a certificate, an encased baseball card that has been personalized by including the staff member’s picture and safety event identified, a stress-release baseball, and a stick of Bazooka gum (similar to what used to come in baseball cards packs). The award is presented to employees in their work area by the HRO and patient safety teams and includes representatives from the executive leadership team (ELT). The safety event identified is described by an ELT member, and all items are presented to the employee. Participation by the leadership team communicates how much the work being done to promote a culture of safety and advance quality health care is appreciated. This action also encourages others in the organization to identify and report safety concerns.¹³

With the rollout of the QI initiative, the volume of nominations submitted quickly increased (eg, approximately 1 every 2 months before to 3 per month following implementation). Frequently, nominations were for actions believed to be within the scope of the employee’s responsibilities. Our institution’s leadership team quickly recognized that, as an organization, not diminishing the importance of the “Good Catch Award” was important. However, the leadership team also wanted to encourage nominations from employees that involved safety issues that were part of the employee’s scope of responsibilities. As a result, 2 additional and equally notable award tiers were established, with specific criteria created for each.¹⁴ The addition of the other awards was instrumental in getting the leadership team to feel confident that all staff were being recognized for their commitment to patient safety.

The original Good Catch Award was labelled as a Level 1 award. The Level 2 safety recognition award, named the HRO Safety Champion Award, is given to employees who stop the line for a safety concern within their scope of practice and also participate as part of a team to investigate and improve processes to avoid recurring safety concerns in the future. For the Level Two award, a certificate is presented to an employee by the hospital’s HRO lead, HRO physician champion, patient safety manager, immediate supervisor, and peers. With the Level 3 award, the Culture of Safety Appreciation Award, individuals are recognized for addressing safety concerns within their assigned scope of responsibilities. Recognition is bestowed by an email of appreciation sent to the employee, acknowledging their commitment to promoting a culture of safety and quality health care. The recipient’s direct supervisor and other hospital leaders are copied on the message.¹⁴ See Table 1 for a comparison of awards.

Our institution’s HRO and patient safety teams utilized many additional venues to disseminate information regarding awardees and their actions. These included our monthly HRO newsletter, monthly safety forums, and biweekly Team Connecticut Healthcare system-wide huddles.

Nomination Process

Awards nominations are submitted via the hospital intranet homepage, where there is an “HRO Safety Award Nomination” icon. Once a staff member clicks the icon, a template opens asking for information, such as the reason for the nomination submission, and then walks them through the template using the CAR (C-context, A-actions, and R-results)¹⁵ format for describing the situation, identifying actions taken, and specifying the outcome of the action. Emails with award nominations can also be sent to the HRO lead, HRO champion, or Patient Safety Committee co-chairs. Calls for nominations are made at several venues attended by employees as well as supervisors. These include monthly safety forums, biweekly Team Connecticut Healthcare system-wide huddles, supervisory staff meetings, department and unit-based staff meetings, and many other formal and informal settings. This QI initiative has allowed us to capture potential awardees through several avenues, including self-nominations. All nominations are reviewed by a safety awards committee. Each committee member ranks the nomination as a Level 1, 2, or 3 award. For nominations where conflicting scores are obtained, the committee discusses the nomination together to resolve discrepancies.

Needed Resources

Material resources required for this QI initiative include certificate paper, plastic baseball card sleeves, stress-release baseballs, and Bazooka gum. The largest resource investment was the time needed to support the initiative. This included the time spent scheduling the Level 1 and 2 award presentations with staff and leadership. Time was also required to put the individual award packages together, which included printing the paper certificates, obtaining awardee pictures, placing them with their safety stories in a plastic baseball card sleeve, and arranging for the hospital photographer to take pictures of the awardees with their peers and leaders.

RESULTS

Prior to this QI initiative launch, 14 awards were given out over the preceding 2-year period. During the initial 18 months of the initiative (December 2020 to June 2022), 59 awards were presented (Level 1, n = 26; Level 2, n = 22; and Level 3, n = 11). Looking further into the Level 1 awards presented, 25 awardees worked in clinical roles and 1 in a nonclinical position (Table 2). The awardees represented multidisciplinary areas, including medical/surgical (med/surg) inpatient units, anesthesia, operating room, pharmacy, mental health clinics, surgical intensive care, specialty care clinics, and nutrition and food services. With the Level 2 awards, 18 clinical staff and 4 nonclinical staff received awards from the areas of med/surg inpatient, outpatient surgical suites, the medical center director’s office, radiology, pharmacy, primary care, facilities management, environmental management, infection prevention, and emergency services. All Level 3 awardees were from clinical areas, including primary care, hospital education, sterile processing, pharmacies, operating rooms, and med/surg inpatient units.

With the inception of this QI initiative, our organization has begun to see trends reflecting increased reporting of both actual and close-call events in JPSR (Figure 1).

With the inclusion of information regarding awardees and their actions in monthly safety forums, attendance at these forums has increased from an average of 64 attendees per month in 2021 to an average of 131 attendees per month in 2022 (Figure 2).

Finally, our organization’s annual All-Employee Survey results have shown incremental increases in staff reporting feeling psychologically safe and not fearing reprisal (Figure 3). It is important to note that there may be other contributing factors to these incremental changes.

Stories From the 3 Award Categories

Level 1 – Good Catch Award. M.S. was assigned as a continuous safety monitor, or “sitter,” on one of the med/surg inpatient units. M.S. arrived at the bedside and asked for a report on the patient at a change in shift. The report stated that the patient was sleeping and had not moved in a while. M.S. set about to perform the functions of a sitter and did her usual tasks in cleaning and tidying the room for the patient for breakfast and taking care of all items in the room, in general. M.S. introduced herself to the patient, who she thought might wake up because of her speaking to him. She thought the patient was in an odd position, and knowing that a patient should be a little further up in the bed, she tried with touch to awaken him to adjust his position. M.S. found that the patient was rather chilly to the touch and immediately became concerned. She continued to attempt to rouse the patient. M.S. called for the nurse and began to adjust the patient’s position. M.S. insisted that the patient was cold and “something was wrong.” A set of vitals was taken and a rapid response team code was called. The patient was immediately transferred to the intensive care unit to receive a higher level of care. If not for the diligence and caring attitude of M.S., this patient may have had a very poor outcome.

Reason for criteria being met: The scope of practice of a sitter is to be present in a patient’s room to monitor for falls and overall safety. This employee noticed that the patient was not responsive to verbal or tactile stimuli. Her immediate reporting of her concern to the nurse resulted in prompt intervention. If she had let the patient be, the patient could have died. The staff member went above and beyond by speaking up and taking action when she had a patient safety concern.

Level 2 – HRO Safety Champion Award. A patient presented to an outpatient clinic for monoclonal antibody (mAb) therapy for a COVID-19 infection; the treatment has been scheduled by the patient’s primary care provider. At that time, outpatient mAb therapy was the recommended care option for patients stable enough to receive treatment in this setting, but it is contraindicated in patients who are too unstable to receive mAb therapy in an outpatient setting, such as those with increased oxygen demands. R.L., a staff nurse, assessed the patient on arrival and found that his vital signs were stable, except for a slightly elevated respiratory rate. Upon questioning, the patient reported that he had increased his oxygen use at home from 2 to 4 L via a nasal cannula. R.L. assessed that the patient was too high-risk for outpatient mAb therapy and had the patient checked into the emergency department (ED) to receive a full diagnostic workup and evaluation by Dr. W., an ED provider. The patient required admission to the hospital for a higher level of care in an inpatient unit because of severe COVID-19 infection. Within 48 hours of admission, the patient’s condition further declined, requiring an upgrade to the medical intensive care unit with progressive interventions. Owing to the clinical assessment skills and prompt action of R.L., the patient was admitted to the hospital instead of receiving treatment in a suboptimal care setting and returning home. Had the patient gone home, his rapid decline could have had serious consequences.

Reason for criteria being met: On a cursory look, the patient may have passed as someone sufficiently stable to undergo outpatient treatment. However, the nurse stopped the line, paid close attention, and picked up on an abnormal vital sign and the projected consequences. The nurse brought the patient to a higher level of care in the ED so that he could get the attention he needed. If this patient was given mAb therapy in the outpatient setting, he would have been discharged and become sicker with the COVID-19 illness. As a result of this incident, R.L. is working with the outpatient clinic and ED staff to enahance triage and evaluation of patients referred for outpatient therapy for COVID-19 infections to prevent a similar event from recurring.

Level 3 – Culture of Safety Appreciation Award. While C.C. was reviewing the hazardous item competencies of the acute psychiatric inpatient staff, it was learned that staff were sniffing patients’ personal items to see if they were “safe” and free from alcohol. This is a potentially dangerous practice, and if fentanyl is present, it can be life-threatening. All patients admitted to acute inpatient psychiatry have all their clothing and personal items checked for hazardous items—pockets are emptied, soles of shoes are lifted, and so on. Staff wear personal protective equipment during this process to mitigate any powders or other harmful substances being inhaled or coming in contact with their skin or clothes. The gloves can be punctured if needles are found in the patient’s belongings. C.C. not only educated the staff on the dangers of sniffing for alcohol during hazardous-item checks, but also looked for further potential safety concerns. An additional identified risk was for needle sticks when such items were found in a patient’s belongings. C.C.’s recommendations included best practices to allow only unopened personal items and have available hospital-issued products as needed. C.C. remembered having a conversation with an employee from the psychiatric emergency room regarding the purchase of puncture-proof gloves to mitigate puncture sticks. C.C. recommended that the same gloves be used by staff on the acute inpatient psychiatry unit during searches for hazardous items.

Reason for criteria being met: The employee works in the hospital education department. It is within her scope of responsibilities to provide ongoing education to staff in order to address potential safety concerns.

DISCUSSION

This QI initiative was undertaken to demonstrate to staff that, in building an organizational culture of safety and advancing quality health care, it is important that staff be encouraged to speak up for safety and be acknowledged for doing so. As part of efforts to continuously build on a safety-first culture, transparency and celebration of successes were demonstrated. This QI initiative demonstrated that a diverse and wide range of employees were reached, from clinical to nonclinical staff, and frontline to supervisory staff, as all were included in the recognition process. While many award nominations were received through the submission of safety concerns to the high-reliability team and patient safety office, several came directly from staff who wanted to recognize their peers for their work, supporting a culture of safety. This showed that staff felt that taking the time to submit a write-up to recognize a peer was an important task. Achieving zero harm for patients and staff alike is a top priority for our institution and guides all decisions, which reinforces that everyone has a responsibility to ensure that safety is always the first consideration. A culture of safety is enhanced by staff recognition. This QI initiative also showed that staff felt valued when they were acknowledged, regardless of the level of recognition they received. The theme of feeling valued came from unsolicited feedback. For example, some direct comments from awardees are presented in the Box.

In addition to endorsing the importance of safe practices to staff, safety award programs can identify gaps in existing standard procedures that can be updated quickly and shared broadly across a health care organization. The authors observed that the existence of the award program gives staff permission to use their voice to speak up when they have questions or concerns related to safety and to proactively engage in safety practices; a cultural shift of this kind informs safety practices and procedures and contributes to a more inspiring workplace. Staff at our organization who have received any of the safety awards, and those who are aware of these awards, have embraced the program readily. At the time of submission of this manuscript, there was a relative paucity of published literature on the details, performance, and impact of such programs. This initiative aims to share a road map highlighting the various dimensions of staff recognition and how the program supports our health care system in fostering a strong, sustainable culture of safety and health care quality. A next step is to formally assess the impact of the awards program on our culture of safety and quality using a psychometrically sound measurement tool, as recommended by TJC,¹⁶ such as the Hospital Survey on Patient Safety Culture.^17,18

CONCLUSION

A health care organization safety awards program is a strategy for building and sustaining a culture of safety. This QI initiative may be valuable to other organizations in the process of establishing a safety awards program of their own. Future research should focus on a formal evaluation of the impact of safety awards programs on patient safety outcomes.

Corresponding author: John S. Murray, PhD, MPH, MSGH, RN, FAAN, 20 Chapel Street, Unit A502, Brookline, MA 02446; [email protected]

Disclosures: None reported.

ABSTRACT

Objective: Promoting a culture of safety is a critical component of improving health care quality. Recognizing staff who stop the line for safety can positively impact the growth of a culture of safety. The purpose of this initiative was to demonstrate to staff the importance of speaking up for safety and being acknowledged for doing so.

Methods: Following a review of the literature on safety awards programs and their role in promoting a culture of safety in health care covering the period 2017 to 2020, a formal process was developed and implemented to disseminate safety awards to employees.

Results: During the initial 18 months of the initiative, a total of 59 awards were presented. The awards were well received by the recipients and other staff members. Within this period, adjustments were made to enhance the scope and reach of the program.

Conclusion: Recognizing staff behaviors that support a culture of safety is important for improving health care quality and employee engagement. Future research should focus on a formal evaluation of the impact of safety awards programs on patient safety outcomes.

Keywords: patient safety, culture of safety, incident reporting, near miss.

A key aspect of improving health care quality is promoting and sustaining a culture of safety in the workplace. Improving the quality of health care services and systems involves making informed choices regarding the types of strategies to implement.¹ An essential aspect of supporting a safety culture is safety-event reporting. To approach the goal of zero harm, all safety events, whether they result in actual harm or are considered near misses, need to be reported. Near-miss events are errors that occur while care is being provided but are detected and corrected before harm reaches the patient.^1-3 Near-miss reporting plays a critical role in helping to identify and correct weaknesses in health care delivery systems and processes.⁴ However, evidence shows that there are a multitude of barriers to the reporting of near-miss events, such as fear of punitive actions, additional workload, unsupportive work environments, a culture with poor psychological safety, knowledge deficit, and lack of recognition of staff who do report near misses.^4-11

According to The Joint Commission (TJC), acknowledging health care team members who recognize and report unsafe conditions that provide insight for improving patient safety is a key method for promoting the reporting of near-miss events.⁶ As a result, some health care organizations and patient safety agencies have started to institute some form of recognition for their employees in the realm of safety.^8-10 The Pennsylvania Patient Safety Authority offers exceptional guidance for creating a safety awards program to promote a culture of safety.¹² Furthermore, TJC supports recognizing individuals and health care teams who identify and report near misses, or who have suggestions for initiatives to promote patient safety, with “good catch” awards. Individuals or teams working to promote and sustain a culture of safety should be recognized for their efforts. Acknowledging “good catches” to reward the identification, communication, and resolution of safety issues is an effective strategy for improving patient safety and health care quality.^6,8

This quality improvement (QI) initiative was undertaken to demonstrate to staff that, in building an organizational culture of safety, it is important that staff be encouraged to speak up for safety and be acknowledged for doing so. If health care organizations want staff to be motivated to report near misses and improve safety and health care quality, the culture needs to shift from focusing on blame to incentivizing individuals and teams to speak up when they have concerns.^8-10 Although deciding which safety actions are worthy of recognition can be challenging, recognizing all safe acts, regardless of how big or small they are perceived to be, is important. This QI initiative aimed to establish a tiered approach to recognize staff members for various categories of safety acts.

METHODS

A review of the literature from January 2017 to May 2020 for peer-reviewed publications regarding how other organizations implemented safety award programs to promote a culture of safety resulted in a dearth of evidence. This prompted us at the Veterans Affairs Connecticut Healthcare System to develop and implement a formal program to disseminate safety awards to employees.

Program Launch and Promotion

In 2020, our institution embarked on a journey to high reliability with the goal of approaching zero harm. As part of efforts to promote a culture of safety, the hospital’s High Reliability Organization (HRO) team worked to develop a safety awards recognition program. Prior to the launch, the hospital’s patient safety committee recognized staff members through the medical center safety event reporting system (the Joint Patient Safety Reporting system [JPSR]) or through direct communication with staff members on safety actions they were engaged in. JPSR is the Veterans Health Administration National Center for Patient Safety incident reporting system for reporting, tracking, and trending of patient incidents in a national database. The award consisted of a certificate presented by the patient safety committee chairpersons to the employee in front of their peers in their respective work area. Hospital leadership was not involved in the safety awards recognition program at that time. No nomination process existed prior to our QI launch.

Once the QI initiative was launched and marketed heavily at staff meetings, we started to receive nominations for actions that were truly exceptional, while many others were submitted for behaviors that were within the day-to-day scope of practice of the staff member. For those early nominations that did not meet criteria for an award, we thanked staff for their submissions with a gentle statement that their nomination did not meet the criteria for an award. After following this practice for a few weeks, we became concerned that if we did not acknowledge the staff who came forward to request recognition for their routine work that supported safety, we could risk losing their engagement in a culture of safety. As such, we decided to create 3 levels of awards to recognize behaviors that went above and beyond while also acknowledging staff for actions within their scope of practice. Additionally, hospital leadership wanted to ensure that all staff recognize that their safety efforts are valued by leadership and that that sense of value will hopefully contribute to a culture of safety over time.

Initially, the single award system was called the “Good Catch Award” to acknowledge staff who go above and beyond to speak up and take action when they have safety concerns. This particular recognition includes a certificate, an encased baseball card that has been personalized by including the staff member’s picture and safety event identified, a stress-release baseball, and a stick of Bazooka gum (similar to what used to come in baseball cards packs). The award is presented to employees in their work area by the HRO and patient safety teams and includes representatives from the executive leadership team (ELT). The safety event identified is described by an ELT member, and all items are presented to the employee. Participation by the leadership team communicates how much the work being done to promote a culture of safety and advance quality health care is appreciated. This action also encourages others in the organization to identify and report safety concerns.¹³

With the rollout of the QI initiative, the volume of nominations submitted quickly increased (eg, approximately 1 every 2 months before to 3 per month following implementation). Frequently, nominations were for actions believed to be within the scope of the employee’s responsibilities. Our institution’s leadership team quickly recognized that, as an organization, not diminishing the importance of the “Good Catch Award” was important. However, the leadership team also wanted to encourage nominations from employees that involved safety issues that were part of the employee’s scope of responsibilities. As a result, 2 additional and equally notable award tiers were established, with specific criteria created for each.¹⁴ The addition of the other awards was instrumental in getting the leadership team to feel confident that all staff were being recognized for their commitment to patient safety.

The original Good Catch Award was labelled as a Level 1 award. The Level 2 safety recognition award, named the HRO Safety Champion Award, is given to employees who stop the line for a safety concern within their scope of practice and also participate as part of a team to investigate and improve processes to avoid recurring safety concerns in the future. For the Level Two award, a certificate is presented to an employee by the hospital’s HRO lead, HRO physician champion, patient safety manager, immediate supervisor, and peers. With the Level 3 award, the Culture of Safety Appreciation Award, individuals are recognized for addressing safety concerns within their assigned scope of responsibilities. Recognition is bestowed by an email of appreciation sent to the employee, acknowledging their commitment to promoting a culture of safety and quality health care. The recipient’s direct supervisor and other hospital leaders are copied on the message.¹⁴ See Table 1 for a comparison of awards.

Our institution’s HRO and patient safety teams utilized many additional venues to disseminate information regarding awardees and their actions. These included our monthly HRO newsletter, monthly safety forums, and biweekly Team Connecticut Healthcare system-wide huddles.

Nomination Process

Awards nominations are submitted via the hospital intranet homepage, where there is an “HRO Safety Award Nomination” icon. Once a staff member clicks the icon, a template opens asking for information, such as the reason for the nomination submission, and then walks them through the template using the CAR (C-context, A-actions, and R-results)¹⁵ format for describing the situation, identifying actions taken, and specifying the outcome of the action. Emails with award nominations can also be sent to the HRO lead, HRO champion, or Patient Safety Committee co-chairs. Calls for nominations are made at several venues attended by employees as well as supervisors. These include monthly safety forums, biweekly Team Connecticut Healthcare system-wide huddles, supervisory staff meetings, department and unit-based staff meetings, and many other formal and informal settings. This QI initiative has allowed us to capture potential awardees through several avenues, including self-nominations. All nominations are reviewed by a safety awards committee. Each committee member ranks the nomination as a Level 1, 2, or 3 award. For nominations where conflicting scores are obtained, the committee discusses the nomination together to resolve discrepancies.

Needed Resources

Material resources required for this QI initiative include certificate paper, plastic baseball card sleeves, stress-release baseballs, and Bazooka gum. The largest resource investment was the time needed to support the initiative. This included the time spent scheduling the Level 1 and 2 award presentations with staff and leadership. Time was also required to put the individual award packages together, which included printing the paper certificates, obtaining awardee pictures, placing them with their safety stories in a plastic baseball card sleeve, and arranging for the hospital photographer to take pictures of the awardees with their peers and leaders.

RESULTS

Prior to this QI initiative launch, 14 awards were given out over the preceding 2-year period. During the initial 18 months of the initiative (December 2020 to June 2022), 59 awards were presented (Level 1, n = 26; Level 2, n = 22; and Level 3, n = 11). Looking further into the Level 1 awards presented, 25 awardees worked in clinical roles and 1 in a nonclinical position (Table 2). The awardees represented multidisciplinary areas, including medical/surgical (med/surg) inpatient units, anesthesia, operating room, pharmacy, mental health clinics, surgical intensive care, specialty care clinics, and nutrition and food services. With the Level 2 awards, 18 clinical staff and 4 nonclinical staff received awards from the areas of med/surg inpatient, outpatient surgical suites, the medical center director’s office, radiology, pharmacy, primary care, facilities management, environmental management, infection prevention, and emergency services. All Level 3 awardees were from clinical areas, including primary care, hospital education, sterile processing, pharmacies, operating rooms, and med/surg inpatient units.

With the inception of this QI initiative, our organization has begun to see trends reflecting increased reporting of both actual and close-call events in JPSR (Figure 1).

With the inclusion of information regarding awardees and their actions in monthly safety forums, attendance at these forums has increased from an average of 64 attendees per month in 2021 to an average of 131 attendees per month in 2022 (Figure 2).

Finally, our organization’s annual All-Employee Survey results have shown incremental increases in staff reporting feeling psychologically safe and not fearing reprisal (Figure 3). It is important to note that there may be other contributing factors to these incremental changes.

Stories From the 3 Award Categories

Level 1 – Good Catch Award. M.S. was assigned as a continuous safety monitor, or “sitter,” on one of the med/surg inpatient units. M.S. arrived at the bedside and asked for a report on the patient at a change in shift. The report stated that the patient was sleeping and had not moved in a while. M.S. set about to perform the functions of a sitter and did her usual tasks in cleaning and tidying the room for the patient for breakfast and taking care of all items in the room, in general. M.S. introduced herself to the patient, who she thought might wake up because of her speaking to him. She thought the patient was in an odd position, and knowing that a patient should be a little further up in the bed, she tried with touch to awaken him to adjust his position. M.S. found that the patient was rather chilly to the touch and immediately became concerned. She continued to attempt to rouse the patient. M.S. called for the nurse and began to adjust the patient’s position. M.S. insisted that the patient was cold and “something was wrong.” A set of vitals was taken and a rapid response team code was called. The patient was immediately transferred to the intensive care unit to receive a higher level of care. If not for the diligence and caring attitude of M.S., this patient may have had a very poor outcome.

Reason for criteria being met: The scope of practice of a sitter is to be present in a patient’s room to monitor for falls and overall safety. This employee noticed that the patient was not responsive to verbal or tactile stimuli. Her immediate reporting of her concern to the nurse resulted in prompt intervention. If she had let the patient be, the patient could have died. The staff member went above and beyond by speaking up and taking action when she had a patient safety concern.

Level 2 – HRO Safety Champion Award. A patient presented to an outpatient clinic for monoclonal antibody (mAb) therapy for a COVID-19 infection; the treatment has been scheduled by the patient’s primary care provider. At that time, outpatient mAb therapy was the recommended care option for patients stable enough to receive treatment in this setting, but it is contraindicated in patients who are too unstable to receive mAb therapy in an outpatient setting, such as those with increased oxygen demands. R.L., a staff nurse, assessed the patient on arrival and found that his vital signs were stable, except for a slightly elevated respiratory rate. Upon questioning, the patient reported that he had increased his oxygen use at home from 2 to 4 L via a nasal cannula. R.L. assessed that the patient was too high-risk for outpatient mAb therapy and had the patient checked into the emergency department (ED) to receive a full diagnostic workup and evaluation by Dr. W., an ED provider. The patient required admission to the hospital for a higher level of care in an inpatient unit because of severe COVID-19 infection. Within 48 hours of admission, the patient’s condition further declined, requiring an upgrade to the medical intensive care unit with progressive interventions. Owing to the clinical assessment skills and prompt action of R.L., the patient was admitted to the hospital instead of receiving treatment in a suboptimal care setting and returning home. Had the patient gone home, his rapid decline could have had serious consequences.

Reason for criteria being met: On a cursory look, the patient may have passed as someone sufficiently stable to undergo outpatient treatment. However, the nurse stopped the line, paid close attention, and picked up on an abnormal vital sign and the projected consequences. The nurse brought the patient to a higher level of care in the ED so that he could get the attention he needed. If this patient was given mAb therapy in the outpatient setting, he would have been discharged and become sicker with the COVID-19 illness. As a result of this incident, R.L. is working with the outpatient clinic and ED staff to enahance triage and evaluation of patients referred for outpatient therapy for COVID-19 infections to prevent a similar event from recurring.

Level 3 – Culture of Safety Appreciation Award. While C.C. was reviewing the hazardous item competencies of the acute psychiatric inpatient staff, it was learned that staff were sniffing patients’ personal items to see if they were “safe” and free from alcohol. This is a potentially dangerous practice, and if fentanyl is present, it can be life-threatening. All patients admitted to acute inpatient psychiatry have all their clothing and personal items checked for hazardous items—pockets are emptied, soles of shoes are lifted, and so on. Staff wear personal protective equipment during this process to mitigate any powders or other harmful substances being inhaled or coming in contact with their skin or clothes. The gloves can be punctured if needles are found in the patient’s belongings. C.C. not only educated the staff on the dangers of sniffing for alcohol during hazardous-item checks, but also looked for further potential safety concerns. An additional identified risk was for needle sticks when such items were found in a patient’s belongings. C.C.’s recommendations included best practices to allow only unopened personal items and have available hospital-issued products as needed. C.C. remembered having a conversation with an employee from the psychiatric emergency room regarding the purchase of puncture-proof gloves to mitigate puncture sticks. C.C. recommended that the same gloves be used by staff on the acute inpatient psychiatry unit during searches for hazardous items.

Reason for criteria being met: The employee works in the hospital education department. It is within her scope of responsibilities to provide ongoing education to staff in order to address potential safety concerns.

DISCUSSION

This QI initiative was undertaken to demonstrate to staff that, in building an organizational culture of safety and advancing quality health care, it is important that staff be encouraged to speak up for safety and be acknowledged for doing so. As part of efforts to continuously build on a safety-first culture, transparency and celebration of successes were demonstrated. This QI initiative demonstrated that a diverse and wide range of employees were reached, from clinical to nonclinical staff, and frontline to supervisory staff, as all were included in the recognition process. While many award nominations were received through the submission of safety concerns to the high-reliability team and patient safety office, several came directly from staff who wanted to recognize their peers for their work, supporting a culture of safety. This showed that staff felt that taking the time to submit a write-up to recognize a peer was an important task. Achieving zero harm for patients and staff alike is a top priority for our institution and guides all decisions, which reinforces that everyone has a responsibility to ensure that safety is always the first consideration. A culture of safety is enhanced by staff recognition. This QI initiative also showed that staff felt valued when they were acknowledged, regardless of the level of recognition they received. The theme of feeling valued came from unsolicited feedback. For example, some direct comments from awardees are presented in the Box.

In addition to endorsing the importance of safe practices to staff, safety award programs can identify gaps in existing standard procedures that can be updated quickly and shared broadly across a health care organization. The authors observed that the existence of the award program gives staff permission to use their voice to speak up when they have questions or concerns related to safety and to proactively engage in safety practices; a cultural shift of this kind informs safety practices and procedures and contributes to a more inspiring workplace. Staff at our organization who have received any of the safety awards, and those who are aware of these awards, have embraced the program readily. At the time of submission of this manuscript, there was a relative paucity of published literature on the details, performance, and impact of such programs. This initiative aims to share a road map highlighting the various dimensions of staff recognition and how the program supports our health care system in fostering a strong, sustainable culture of safety and health care quality. A next step is to formally assess the impact of the awards program on our culture of safety and quality using a psychometrically sound measurement tool, as recommended by TJC,¹⁶ such as the Hospital Survey on Patient Safety Culture.^17,18

CONCLUSION

A health care organization safety awards program is a strategy for building and sustaining a culture of safety. This QI initiative may be valuable to other organizations in the process of establishing a safety awards program of their own. Future research should focus on a formal evaluation of the impact of safety awards programs on patient safety outcomes.

Corresponding author: John S. Murray, PhD, MPH, MSGH, RN, FAAN, 20 Chapel Street, Unit A502, Brookline, MA 02446; [email protected]

Disclosures: None reported.