Mixed Topics

The US Food and Drug Administration has expanded its guidance on medical device sterilization to include vaporized hydrogen peroxide, according to an agency press release issued on January 8.

The update is intended to promote wider use of vaporized hydrogen peroxide (VHP) as a viable alternative to ethylene oxide (EtO). The FDA guidance on sterile devices has been revised to include VHP.

The acceptance of VHP as an Established Category A method of sterilization is another step toward the FDA’s larger goal of reducing EtO, according to the release.

Sterilization is essential for certain medical devices, but the use of EtO, currently the most common method, involves the release of emissions that are potentially harmful to health, and the FDA seeks to identify safe and effective alternatives to reduce risk to the environment and communities where device sterilization occurs. Current Established Category A sterilization methods include moist heat, dry heat, EtO, and radiation. 

FDA

“Vaporized hydrogen peroxide’s addition as an established sterilization method helps us build a more resilient supply chain for sterilized devices that can help prevent medical device shortages,” Suzanne Schwartz, MD, director of the Office of Strategic Partnerships and Technology Innovation in the FDA’s Center for Devices and Radiological Health, said in the press release. “As innovations in sterilization advance, the FDA will continue to seek additional modalities that deliver safe and effective sterilization methods that best protect public health,” she said.

The FDA has supported the development of EtO alternatives since 2019, and remains committed to reducing EtO emissions and also to avoiding potential device shortages, according to the release.

“Ethylene oxide is highly flammable and carcinogenic and poses exposure-related safety concerns for reprocessing staff, as well as environmental risks,” said Venkataraman R. Muthusamy, MD, AGAF, of the University of California, Los Angeles, in an interview. “These risks have led some states or regions to ban or limit its use, but despite these risks, it is currently the most commonly used sterilization technique for medical devices in the United States,” he said. Therefore, coming up with alternatives has been a high priority for the FDA, he added.

VHP has several advantages over EtO, Dr. Muthusamy said. VHP breaks down safely into water and oxygen, with low residual levels after exposure, and has no known oxidation or discoloration effects. In addition, VHP has a low temperature, and should theoretically be safe to use with endoscopes, although data are lacking, he said.

Dr. Muthusamy said that he was not yet too familiar with VHP as a technique, in part because most accessories in GI are single-use.

Primary issues to expanding the use of vaporized hydrogen peroxide as a sterilizing agent in GI clinical practice include availability and the cost of acquiring the devices needed, Dr. Muthusamy told GI & Hepatology News. “Also, the comparative efficacy of this technique in sterilizing GI endoscopes to ethylene oxide and the impact of VHP on scope durability and performance will need to be assessed, and the impact of VHP on the health and safety of reprocessing staff will need to be assessed and monitored,” he said.

There is an interest in the GI community in “green” endoscopy and reducing waste, Dr. Muthusamy said. If an inexpensive, safe, and cost-effective option for sterilization of other devices beyond endoscopes exists, “perhaps we could reduce our use of some disposables as well,” he said.

Dr. Muthusamy had no financial conflicts to disclose. 

The US Food and Drug Administration has expanded its guidance on medical device sterilization to include vaporized hydrogen peroxide, according to an agency press release issued on January 8.

The update is intended to promote wider use of vaporized hydrogen peroxide (VHP) as a viable alternative to ethylene oxide (EtO). The FDA guidance on sterile devices has been revised to include VHP.

The acceptance of VHP as an Established Category A method of sterilization is another step toward the FDA’s larger goal of reducing EtO, according to the release.

Sterilization is essential for certain medical devices, but the use of EtO, currently the most common method, involves the release of emissions that are potentially harmful to health, and the FDA seeks to identify safe and effective alternatives to reduce risk to the environment and communities where device sterilization occurs. Current Established Category A sterilization methods include moist heat, dry heat, EtO, and radiation. 

FDA

“Vaporized hydrogen peroxide’s addition as an established sterilization method helps us build a more resilient supply chain for sterilized devices that can help prevent medical device shortages,” Suzanne Schwartz, MD, director of the Office of Strategic Partnerships and Technology Innovation in the FDA’s Center for Devices and Radiological Health, said in the press release. “As innovations in sterilization advance, the FDA will continue to seek additional modalities that deliver safe and effective sterilization methods that best protect public health,” she said.

The FDA has supported the development of EtO alternatives since 2019, and remains committed to reducing EtO emissions and also to avoiding potential device shortages, according to the release.

“Ethylene oxide is highly flammable and carcinogenic and poses exposure-related safety concerns for reprocessing staff, as well as environmental risks,” said Venkataraman R. Muthusamy, MD, AGAF, of the University of California, Los Angeles, in an interview. “These risks have led some states or regions to ban or limit its use, but despite these risks, it is currently the most commonly used sterilization technique for medical devices in the United States,” he said. Therefore, coming up with alternatives has been a high priority for the FDA, he added.

VHP has several advantages over EtO, Dr. Muthusamy said. VHP breaks down safely into water and oxygen, with low residual levels after exposure, and has no known oxidation or discoloration effects. In addition, VHP has a low temperature, and should theoretically be safe to use with endoscopes, although data are lacking, he said.

Dr. Muthusamy said that he was not yet too familiar with VHP as a technique, in part because most accessories in GI are single-use.

Primary issues to expanding the use of vaporized hydrogen peroxide as a sterilizing agent in GI clinical practice include availability and the cost of acquiring the devices needed, Dr. Muthusamy told GI & Hepatology News. “Also, the comparative efficacy of this technique in sterilizing GI endoscopes to ethylene oxide and the impact of VHP on scope durability and performance will need to be assessed, and the impact of VHP on the health and safety of reprocessing staff will need to be assessed and monitored,” he said.

There is an interest in the GI community in “green” endoscopy and reducing waste, Dr. Muthusamy said. If an inexpensive, safe, and cost-effective option for sterilization of other devices beyond endoscopes exists, “perhaps we could reduce our use of some disposables as well,” he said.

Dr. Muthusamy had no financial conflicts to disclose. 

The US Food and Drug Administration has expanded its guidance on medical device sterilization to include vaporized hydrogen peroxide, according to an agency press release issued on January 8.

The update is intended to promote wider use of vaporized hydrogen peroxide (VHP) as a viable alternative to ethylene oxide (EtO). The FDA guidance on sterile devices has been revised to include VHP.

The acceptance of VHP as an Established Category A method of sterilization is another step toward the FDA’s larger goal of reducing EtO, according to the release.

Sterilization is essential for certain medical devices, but the use of EtO, currently the most common method, involves the release of emissions that are potentially harmful to health, and the FDA seeks to identify safe and effective alternatives to reduce risk to the environment and communities where device sterilization occurs. Current Established Category A sterilization methods include moist heat, dry heat, EtO, and radiation. 

FDA

“Vaporized hydrogen peroxide’s addition as an established sterilization method helps us build a more resilient supply chain for sterilized devices that can help prevent medical device shortages,” Suzanne Schwartz, MD, director of the Office of Strategic Partnerships and Technology Innovation in the FDA’s Center for Devices and Radiological Health, said in the press release. “As innovations in sterilization advance, the FDA will continue to seek additional modalities that deliver safe and effective sterilization methods that best protect public health,” she said.

The FDA has supported the development of EtO alternatives since 2019, and remains committed to reducing EtO emissions and also to avoiding potential device shortages, according to the release.

“Ethylene oxide is highly flammable and carcinogenic and poses exposure-related safety concerns for reprocessing staff, as well as environmental risks,” said Venkataraman R. Muthusamy, MD, AGAF, of the University of California, Los Angeles, in an interview. “These risks have led some states or regions to ban or limit its use, but despite these risks, it is currently the most commonly used sterilization technique for medical devices in the United States,” he said. Therefore, coming up with alternatives has been a high priority for the FDA, he added.

VHP has several advantages over EtO, Dr. Muthusamy said. VHP breaks down safely into water and oxygen, with low residual levels after exposure, and has no known oxidation or discoloration effects. In addition, VHP has a low temperature, and should theoretically be safe to use with endoscopes, although data are lacking, he said.

Dr. Muthusamy said that he was not yet too familiar with VHP as a technique, in part because most accessories in GI are single-use.

Primary issues to expanding the use of vaporized hydrogen peroxide as a sterilizing agent in GI clinical practice include availability and the cost of acquiring the devices needed, Dr. Muthusamy told GI & Hepatology News. “Also, the comparative efficacy of this technique in sterilizing GI endoscopes to ethylene oxide and the impact of VHP on scope durability and performance will need to be assessed, and the impact of VHP on the health and safety of reprocessing staff will need to be assessed and monitored,” he said.

There is an interest in the GI community in “green” endoscopy and reducing waste, Dr. Muthusamy said. If an inexpensive, safe, and cost-effective option for sterilization of other devices beyond endoscopes exists, “perhaps we could reduce our use of some disposables as well,” he said.

Dr. Muthusamy had no financial conflicts to disclose. 

TOPLINE:

Allergens were present in more than half of evaluable over-the-counter (OTC) topical scar products, study finds. 

METHODOLOGY:

• OTC topical scar treatments have the potential to cause an allergic reaction, but the prevalence of North American Contact Dermatitis Group (NACDG) core allergens in these products is unclear.
• Researchers used the word scar in a query of Amazon.com and four other retail websites to identify topical scar products for consumers and noted the list of ingredients.
• The investigators also surveyed the American Contact Dermatitis Society’s Contact Allergen Management Program (CAMP), a resource that helps patients with allergies find personal care products that are safe to use, for pertinent products.

TAKEAWAY: 

• The search query identified 156 products. Of these, 119 (76.2%) were gels, creams, or oils and 37 (23.7%) were sheets, strips, or tape.
• Of the 125 products that had a list of ingredients, 69 (55.2%) contained at least one NACDG allergen and 45 (36%) contained more than one.
• The top six most common allergens listed in the ingredients were fragrance (16.8%), phenoxyethanol (16.8%), parabens (14.4%), panthenol (12.8%), sodium benzoate (9.60%), and ethylhexylglycerin (8%).
• Analysis of CAMP revealed that the program only had five unique scar products in its list, suggesting that CAMP might not be a reliable source of scar product information for patients with known allergies to pertinent NACDG allergens.

IN PRACTICE:

“Patients can consider trying a ‘use test’ on the inner forearm before applying to the surgical site,” the authors wrote. “It may reveal they are sensitive or sensitized by a product. 

SOURCE:

First author Meera Kattapuram, MD, of the Department of Internal Medicine at Mount Sinai Hospital, New York, led the study, published in the February issue of Dermatologic Surgery.  

LIMITATIONS:

Limitations include the selection of five retailers and the top 100 products from each website and the potential for ingredient list inaccuracies. 

DISCLOSURES:

The authors reported having no financial conflicts of interest. The research was supported by a grant from the National Institutes of Health/National Cancer Institute. 

A version of this article appeared on Medscape.com.

TOPLINE:

Allergens were present in more than half of evaluable over-the-counter (OTC) topical scar products, study finds. 

METHODOLOGY:

• OTC topical scar treatments have the potential to cause an allergic reaction, but the prevalence of North American Contact Dermatitis Group (NACDG) core allergens in these products is unclear.
• Researchers used the word scar in a query of Amazon.com and four other retail websites to identify topical scar products for consumers and noted the list of ingredients.
• The investigators also surveyed the American Contact Dermatitis Society’s Contact Allergen Management Program (CAMP), a resource that helps patients with allergies find personal care products that are safe to use, for pertinent products.

TAKEAWAY: 

• The search query identified 156 products. Of these, 119 (76.2%) were gels, creams, or oils and 37 (23.7%) were sheets, strips, or tape.
• Of the 125 products that had a list of ingredients, 69 (55.2%) contained at least one NACDG allergen and 45 (36%) contained more than one.
• The top six most common allergens listed in the ingredients were fragrance (16.8%), phenoxyethanol (16.8%), parabens (14.4%), panthenol (12.8%), sodium benzoate (9.60%), and ethylhexylglycerin (8%).
• Analysis of CAMP revealed that the program only had five unique scar products in its list, suggesting that CAMP might not be a reliable source of scar product information for patients with known allergies to pertinent NACDG allergens.

IN PRACTICE:

“Patients can consider trying a ‘use test’ on the inner forearm before applying to the surgical site,” the authors wrote. “It may reveal they are sensitive or sensitized by a product. 

SOURCE:

First author Meera Kattapuram, MD, of the Department of Internal Medicine at Mount Sinai Hospital, New York, led the study, published in the February issue of Dermatologic Surgery.  

LIMITATIONS:

Limitations include the selection of five retailers and the top 100 products from each website and the potential for ingredient list inaccuracies. 

DISCLOSURES:

The authors reported having no financial conflicts of interest. The research was supported by a grant from the National Institutes of Health/National Cancer Institute. 

A version of this article appeared on Medscape.com.

TOPLINE:

Allergens were present in more than half of evaluable over-the-counter (OTC) topical scar products, study finds. 

METHODOLOGY:

• OTC topical scar treatments have the potential to cause an allergic reaction, but the prevalence of North American Contact Dermatitis Group (NACDG) core allergens in these products is unclear.
• Researchers used the word scar in a query of Amazon.com and four other retail websites to identify topical scar products for consumers and noted the list of ingredients.
• The investigators also surveyed the American Contact Dermatitis Society’s Contact Allergen Management Program (CAMP), a resource that helps patients with allergies find personal care products that are safe to use, for pertinent products.

TAKEAWAY: 

• The search query identified 156 products. Of these, 119 (76.2%) were gels, creams, or oils and 37 (23.7%) were sheets, strips, or tape.
• Of the 125 products that had a list of ingredients, 69 (55.2%) contained at least one NACDG allergen and 45 (36%) contained more than one.
• The top six most common allergens listed in the ingredients were fragrance (16.8%), phenoxyethanol (16.8%), parabens (14.4%), panthenol (12.8%), sodium benzoate (9.60%), and ethylhexylglycerin (8%).
• Analysis of CAMP revealed that the program only had five unique scar products in its list, suggesting that CAMP might not be a reliable source of scar product information for patients with known allergies to pertinent NACDG allergens.

IN PRACTICE:

“Patients can consider trying a ‘use test’ on the inner forearm before applying to the surgical site,” the authors wrote. “It may reveal they are sensitive or sensitized by a product. 

SOURCE:

First author Meera Kattapuram, MD, of the Department of Internal Medicine at Mount Sinai Hospital, New York, led the study, published in the February issue of Dermatologic Surgery.  

LIMITATIONS:

Limitations include the selection of five retailers and the top 100 products from each website and the potential for ingredient list inaccuracies. 

DISCLOSURES:

The authors reported having no financial conflicts of interest. The research was supported by a grant from the National Institutes of Health/National Cancer Institute. 

A version of this article appeared on Medscape.com.

TOPLINE:

Oral antibiotics may be a safe alternative to receiving prolonged intravenous (IV) antibiotics, according to a recent observational study published in JAMA Network Open.

METHODOLOGY:

• Patients receiving antibiotics through an IV line risk developing a secondary infection; antibiotics received orally are considered safer.
• Researchers analyzed observational data from 914 adults with uncomplicated gram-negative bacteremia who received care in four hospitals in Denmark between 2018 and 2021.
• The outcomes of patients who were switched to oral antibiotics within 4 days after a positive blood culture were compared with those who continued to receive IV antibiotics for at least 5 days after the blood culture; participants in both groups received antibiotics for 7-14 days.
• Researchers assessed mortality rates over a 90-day window and used a target trial emulation method to conduct the study.

TAKEAWAY:

• Overall, 14.3% of patients who received prolonged IV treatment died, compared with 6.9% in the oral antibiotics group.
• In an intention-to-treat analysis, patients who were switched to oral antibiotics had a 22% lower risk for death within 90 days of initiation of treatment (relative risk [RR], 0.78; 95% CI, 0.60-1.10).
• In a per-protocol analysis, patients who switched to the oral route had a 1% lower odds of dying within 90 days (RR, 0.99; 95% CI, 0.70-1.40).
• Individuals who were switched to oral antibiotic treatment were younger than those who continued to receive antibiotics via the IV route (median age, 73 vs 76 years, respectively), had fewer comorbidities (four vs five), and were more likely to have community-acquired gram-negative bacteremia (89.4% vs 80.9%).

IN PRACTICE:

“These findings suggest that the mortality associated with early antibiotic stepdown treatment is comparable to that associated with receiving prolonged IV antibiotic treatment for individuals with uncomplicated gram-negative bacteremia,” the authors of the study wrote.

SOURCE:

The study was led by Sandra Tingsgård, MD, of the Center of Research & Department of Infectious Diseases at Copenhagen University Hospital–Amager and Hvidovre in Denmark.

LIMITATIONS:

The study was based on data from electronic health records, so some factors may not have been recorded or considered. The researchers identified few cases of multidrug-resistant infections, and the findings may not apply to those cases. Complicated cases and people who were not stabilized by day 4 were excluded from the analysis.

DISCLOSURES:

The authors report no disclosures or sources of funding.

A version of this article appeared on Medscape.com.

TOPLINE:

Oral antibiotics may be a safe alternative to receiving prolonged intravenous (IV) antibiotics, according to a recent observational study published in JAMA Network Open.

METHODOLOGY:

• Patients receiving antibiotics through an IV line risk developing a secondary infection; antibiotics received orally are considered safer.
• Researchers analyzed observational data from 914 adults with uncomplicated gram-negative bacteremia who received care in four hospitals in Denmark between 2018 and 2021.
• The outcomes of patients who were switched to oral antibiotics within 4 days after a positive blood culture were compared with those who continued to receive IV antibiotics for at least 5 days after the blood culture; participants in both groups received antibiotics for 7-14 days.
• Researchers assessed mortality rates over a 90-day window and used a target trial emulation method to conduct the study.

TAKEAWAY:

• Overall, 14.3% of patients who received prolonged IV treatment died, compared with 6.9% in the oral antibiotics group.
• In an intention-to-treat analysis, patients who were switched to oral antibiotics had a 22% lower risk for death within 90 days of initiation of treatment (relative risk [RR], 0.78; 95% CI, 0.60-1.10).
• In a per-protocol analysis, patients who switched to the oral route had a 1% lower odds of dying within 90 days (RR, 0.99; 95% CI, 0.70-1.40).
• Individuals who were switched to oral antibiotic treatment were younger than those who continued to receive antibiotics via the IV route (median age, 73 vs 76 years, respectively), had fewer comorbidities (four vs five), and were more likely to have community-acquired gram-negative bacteremia (89.4% vs 80.9%).

IN PRACTICE:

“These findings suggest that the mortality associated with early antibiotic stepdown treatment is comparable to that associated with receiving prolonged IV antibiotic treatment for individuals with uncomplicated gram-negative bacteremia,” the authors of the study wrote.

SOURCE:

The study was led by Sandra Tingsgård, MD, of the Center of Research & Department of Infectious Diseases at Copenhagen University Hospital–Amager and Hvidovre in Denmark.

LIMITATIONS:

The study was based on data from electronic health records, so some factors may not have been recorded or considered. The researchers identified few cases of multidrug-resistant infections, and the findings may not apply to those cases. Complicated cases and people who were not stabilized by day 4 were excluded from the analysis.

DISCLOSURES:

The authors report no disclosures or sources of funding.

A version of this article appeared on Medscape.com.

TOPLINE:

Oral antibiotics may be a safe alternative to receiving prolonged intravenous (IV) antibiotics, according to a recent observational study published in JAMA Network Open.

METHODOLOGY:

• Patients receiving antibiotics through an IV line risk developing a secondary infection; antibiotics received orally are considered safer.
• Researchers analyzed observational data from 914 adults with uncomplicated gram-negative bacteremia who received care in four hospitals in Denmark between 2018 and 2021.
• The outcomes of patients who were switched to oral antibiotics within 4 days after a positive blood culture were compared with those who continued to receive IV antibiotics for at least 5 days after the blood culture; participants in both groups received antibiotics for 7-14 days.
• Researchers assessed mortality rates over a 90-day window and used a target trial emulation method to conduct the study.

TAKEAWAY:

• Overall, 14.3% of patients who received prolonged IV treatment died, compared with 6.9% in the oral antibiotics group.
• In an intention-to-treat analysis, patients who were switched to oral antibiotics had a 22% lower risk for death within 90 days of initiation of treatment (relative risk [RR], 0.78; 95% CI, 0.60-1.10).
• In a per-protocol analysis, patients who switched to the oral route had a 1% lower odds of dying within 90 days (RR, 0.99; 95% CI, 0.70-1.40).
• Individuals who were switched to oral antibiotic treatment were younger than those who continued to receive antibiotics via the IV route (median age, 73 vs 76 years, respectively), had fewer comorbidities (four vs five), and were more likely to have community-acquired gram-negative bacteremia (89.4% vs 80.9%).

IN PRACTICE:

“These findings suggest that the mortality associated with early antibiotic stepdown treatment is comparable to that associated with receiving prolonged IV antibiotic treatment for individuals with uncomplicated gram-negative bacteremia,” the authors of the study wrote.

SOURCE:

The study was led by Sandra Tingsgård, MD, of the Center of Research & Department of Infectious Diseases at Copenhagen University Hospital–Amager and Hvidovre in Denmark.

LIMITATIONS:

The study was based on data from electronic health records, so some factors may not have been recorded or considered. The researchers identified few cases of multidrug-resistant infections, and the findings may not apply to those cases. Complicated cases and people who were not stabilized by day 4 were excluded from the analysis.

DISCLOSURES:

The authors report no disclosures or sources of funding.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.

The number of state psychiatric hospital beds has hit a historic low with about 11 beds per 100,000 population, a new report showed.

More than half of those beds (52%) were occupied by forensic patients, individuals with serious mental illness (SMI) who were committed to the state hospital through the criminal legal system to help establish competency for trial.

“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.

Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.

To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.

Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.

The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.

The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.

About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.

“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”

There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.

Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.

Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.

“States must strive for prevention over punishment,” the report concluded.

There was no study funding reported, nor were disclosures available.
 

A version of this article appeared on Medscape.com.

The number of state psychiatric hospital beds has hit a historic low with about 11 beds per 100,000 population, a new report showed.

More than half of those beds (52%) were occupied by forensic patients, individuals with serious mental illness (SMI) who were committed to the state hospital through the criminal legal system to help establish competency for trial.

“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.

Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.

To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.

Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.

The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.

The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.

About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.

“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”

There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.

Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.

Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.

“States must strive for prevention over punishment,” the report concluded.

There was no study funding reported, nor were disclosures available.
 

A version of this article appeared on Medscape.com.

The number of state psychiatric hospital beds has hit a historic low with about 11 beds per 100,000 population, a new report showed.

More than half of those beds (52%) were occupied by forensic patients, individuals with serious mental illness (SMI) who were committed to the state hospital through the criminal legal system to help establish competency for trial.

“The shortage of psychiatric beds has real consequences for people with SMI — some will wait months in jail despite not yet being found guilty of a crime, others will be denied admission despite being critically ill, and others still will be discharged prematurely onto the streets to free up beds, where they may grow sicker and be at an elevated risk of mortality,” wrote report coauthors Shanti Silver of the Treatment Advocacy Center (TAC) in Arlington and Elizabeth Sinclair Hanq of the National Association of State Mental Health Program Directors in Alexandria, Virginia.

Published online on January 24, Prevention Over Punishment: Finding the Right Balance of Civil and Forensic State Psychiatric Hospital Beds recommends that state and local governments work together to open additional state psychiatric hospital beds for civil and forensic patients with SMI.

To obtain data about the availability of state psychiatric hospital beds, TAC surveyed state officials from April to August 2023. Official responses were provided by 41 states and the District of Columbia.

Information for the remaining states was gathered from state websites, media articles, preexisting reports, hospital admission staff, or personal contacts living in those states.

The median occupancy rate for state-run hospitals in the new report was 90%, well above the 85% level investigators say usually signals a bed shortage. Overall, 73% of states reported occupancy rates above that level, with 11 states operating at 95% capacity.

The proportion of state psychiatric beds occupied by forensic patients has increased by 12% since 2016, largely driven by the growing number of individuals awaiting a competency determination to stand trial. Before they occupy these beds, however, people with SMI can languish in jail for months or even years, waiting for a bed to open.

About 15% of all state hospital beds and 31% of forensic beds across 34 states were occupied by individuals who had been found not guilty of a crime by reasons of insanity.

“The prioritization of admission of forensic patients has effectively created a system where someone must be arrested to access a state hospital bed,” report coauthor Lisa Dailey, TAC executive director, told this news organization. “But there are not enough beds for forensic patients either; thousands of inmates are waiting in jail on any given day for a bed to open up.”

There are several factors contributing to the scarcity of beds, including an existing hospital staffing shortage made worse by the COVID-19 pandemic and a lack of appropriate discharge facilities.

Report authors offered a number of recommendations to federal, state, and local officials to increase the availability of state-run psychiatric hospital beds, including infrastructure changes involving recruiting and retaining staff for state hospitals and funding new discharge or step-down facilities so that patients have a place to recover when they leave the hospital.

Policy changes could also help, the report noted. Policymakers should consider “dismiss and transfer” procedures to address the backlog of nearly 6000 people with SMI waiting for a state hospital bed to achieve competency to stand trial. With “dismiss and transfer,” criminal charges are dismissed or suspended while an application for civil commitment is filed in the probate court. Once a civil commitment order has been issued, the individual is released to an outpatient commitment program for treatment.

“States must strive for prevention over punishment,” the report concluded.

There was no study funding reported, nor were disclosures available.
 

A version of this article appeared on Medscape.com.

Emergencies happen anywhere and anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. 'Is There a Doctor in the House?' is a Medscape Medical News series telling these stories.

Bill Madden, MD: It was a Saturday in October of 1996. I had gone to my favorite plant nursery in Tucson with my wife, Beth, and two of my kids, Zach and Katya, who were 9 years old. I went to the back of the nursery to use the bathroom, and I heard two of the workers yelling at each other. The tone was angry. 

I went back up to the front, and Zach said that he was bored. He asked if he could go to the car and get a book, so I gave him my car keys and told him to be careful crossing the street. 

Ron Quintia, DDS: It was late in the afternoon, probably close to 4 PM. I was also at the nursery picking up some plants. 

The noise came out of nowhere. Boom! Boom! Boom! I thought, Wow, that sounds like a gun. But no, it can’t be a gun. This is a plant nursery. 

BM: When I heard the rounds being fired, I knew what that sound meant. I was in the Army for 20 years doing critical care for kids. 

I turned and a young man came running toward me out of the sun. It was hard to see, but I realized a second guy was running about 10 feet behind him. Both men were screaming. 

My wife was about 10 feet away behind a raised planter with Katya. I yelled for them to get down as I dove for the ground.

The first guy, a young Hispanic man, tried to escape through some bushes. But the shooter was catching up. I recognized him. He was from Ethiopia and worked at the nursery. I had talked to him a week earlier about his life; he used to be a farmer.

Now, he was holding a 9-mm automatic — silver, very shiny. He shot the Hispanic man twice in the chest. Then he ran toward the back of the nursery. 

RQ: When I realized what was happening, I crouched down, so I couldn’t see very much. But I heard someone screaming, “He has a gun! He has a gun!” And then I heard more shots. 

BM: I yelled at my wife, “Get out!” Then I ran for the phone at the kiosk desk to call 911. This was before most people had cell phones. But the phone was hooked up to the paging system for the nursery, and I couldn’t get it to work. I turned and ran for the wounded man.

RQ: I got to the victim first. Both lungs had been hit, and I could hear he had sucking chest wounds. He was bleeding out of his mouth, saying, “I’m going to die. I’m going to die.” I told him, “You’re not going to die,” while thinking to myself, He’s going to die. 

BM: I had never met Ron before, but we started working on the patient together. Both of his lungs were collapsing. With sucking chest wounds, the critical issue is to seal up the holes. So normally, you slap a Vaseline dressing on and tape it up real good. But obviously, we didn’t have anything. 

Ron and I took off our shirts and used them to bandage the man’s chest. He wasn’t looking good, starting to turn blue. He was dying. We were yelling for someone to call an ambulance. 

And then suddenly, the shooter was back. He was standing there yelling at us to leave so he could kill the man we were helping. The 9-mil was in his hand, ready to fire. He kept screaming, “I’m not a monkey! I’m not a monkey!”

RQ: The guy was less than 10 feet from us, and we were facing down this gun that looked like a cannon. I thought, This is it. It’s curtains. I’m going to die. We’re all going to die. 

BM: I had decided I would die too. I wasn’t frightened though. It’s hard to explain. Dying was okay because I’d gotten my family away. I just had to stay alive as long as I could in order to provide for the victim. 

It’s what I signed up for when I chose to be a doc — to do whatever was needed. And if I got killed in the process, that was just part of the story. So we started talking to the shooter.

I said, “No, you’re not a monkey. You’re a man, a human being. It’s okay.” We pleaded with him to put the weapon down and not to shoot. We did not leave the patient. Finally, the shooter ran off toward the back of the nursery.

RQ: About 30 seconds after that, we heard two more shots from that direction. 

Then there were sirens, and the place was suddenly crawling with police. The paramedics came and took over. I got up and got out of the way.

BM: A young woman ran up, her mouth covered with blood. She said that there was another victim in the back. I asked a police officer to go with us to check. We started for the back when suddenly, we heard yelling and many rounds being fired. The officer ran in the direction of the shooting. 

The woman and I kept walking through rows of plants and trees. It was like moving through a jungle. Finally, we reached the other victim, an American Indian man, lying on his back. He had a chest wound and a head wound. No respirations. No radial pulse. No carotid pulse. I pronounced him dead.

Then I heard a voice calling for help. There were two women hiding nearby in the bushes. I led them to where the police cars were.

Another officer came over and told me that they had the shooter. The police had shot him in the leg and arrested him.

RQ: The police kept us there for quite some time. Meanwhile, the TV crews arrived. I had a black Toyota 4Runner at the time. My family was home watching the news, and a bulletin came on about a shooting in Midtown. The camera panned around the area, and my wife saw our car on the street! They were all worried until I could call and let them know that I was okay.

BM: As we waited, the sun went down, and I was getting cold. My shirt was a bloody mess. Ron and I just sat there quietly, not saying a whole heck of a lot. 

Finally, an officer took our statements, a detective interviewed us, and they let us leave. I called Beth, and she and the kids came and got me. 

At home, we talked to the kids, letting them express their fears. We put them to bed. I didn’t sleep that night. 

RQ: I can’t describe how weird it was going home with this guy’s blood on my body. Needing to take a bath. Trying to get rid of the stench of what could have been a brutal killing. But it wasn’t. At least, not for our patient. 

Thankfully, there are three hospitals within a stone’s throw of the nursery. The paramedics got the man we helped to Tucson Medical Center and into the OR immediately. Then the general surgeons could get chest tubes in him to reinflate his lungs.

BM: The doctor who treated him called me later. He said that when they put the chest tubes in, they got a liter and a half of blood out of him. If it had taken another 10 minutes or so to get there, he very likely would’ve been dead on arrival in the emergency room. 

RQ: I checked on him at the hospital the next day, and he was doing okay. That was the last time I saw him. 

I only saw the shooter again in court. Dr. Madden and I were both called as witnesses at his trial. He was tried for capital murder and 12 charges of aggravated assault for every person who was at the nursery. He was found guilty on all of them and sentenced to 35 years to life in prison. 

BM: I don’t think the shooter was very well represented in court. It’s not that he didn’t kill one person and critically wound another. He did, and he deserves to be punished for that. But his story wasn’t told.

I knew that during the civil war in Ethiopia, his family had been killed by Cuban soldiers sent there to help the pro-communist government. In a way, I thought of him as two different people: the shooter and the farmer. They are both in prison, but only one of them deserves to be there.

After it happened, I wanted to visit the farmer in the hospital and tell him that, despite what he had done, he was not alone. Our family cared about him. The police wouldn’t let me see him, so I asked the Catholic chaplain of the hospital to go. He gave him my message: that despite all the sorrow and pain, in some distant way, I understood. I respected him as a human being. And I was praying for him.

RQ: It’s safe to say that the experience will affect me forever. For months, even years afterward, if somebody would ask me about what happened, I would start to cry. I would sit in the parking lot of my favorite running trail and worry about the people driving in. If I heard a car backfire, I thought about gunshots. 

It was terrifying. And thank God I’ve never found myself in that position again. But I suspect I’d probably react the same way. This is our calling. It’s what we do — protecting other people and taking care of them.

BM: I’d always wondered what I would do in a situation like this. I knew I could function in a critical care situation, a child in a hospital or in the back of an ambulance. But could I do it when my own life was threatened? I found out that I could, and that was really important to me. 

RQ: It was one of those great lessons in life. You realize how lucky you are and that your life can be snatched away from you in a millisecond. I went to a nursery to buy plants for my yard, and instead I ended up helping to save a life.Bill Madden, MD, is a retired US Army colonel and pediatrician, formerly an associate professor of Clinical Pediatrics at the College of Medicine of the University of Arizona, Tucson. 

Ron Quintia, DDS, is an oral and maxillofacial surgeon at Southern Arizona Oral & Maxillofacial Surgery in Tucson, Arizona. 

A version of this article appeared on Medscape.com .

Emergencies happen anywhere and anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. 'Is There a Doctor in the House?' is a Medscape Medical News series telling these stories.

Bill Madden, MD: It was a Saturday in October of 1996. I had gone to my favorite plant nursery in Tucson with my wife, Beth, and two of my kids, Zach and Katya, who were 9 years old. I went to the back of the nursery to use the bathroom, and I heard two of the workers yelling at each other. The tone was angry. 

I went back up to the front, and Zach said that he was bored. He asked if he could go to the car and get a book, so I gave him my car keys and told him to be careful crossing the street. 

Ron Quintia, DDS: It was late in the afternoon, probably close to 4 PM. I was also at the nursery picking up some plants. 

The noise came out of nowhere. Boom! Boom! Boom! I thought, Wow, that sounds like a gun. But no, it can’t be a gun. This is a plant nursery. 

BM: When I heard the rounds being fired, I knew what that sound meant. I was in the Army for 20 years doing critical care for kids. 

I turned and a young man came running toward me out of the sun. It was hard to see, but I realized a second guy was running about 10 feet behind him. Both men were screaming. 

My wife was about 10 feet away behind a raised planter with Katya. I yelled for them to get down as I dove for the ground.

The first guy, a young Hispanic man, tried to escape through some bushes. But the shooter was catching up. I recognized him. He was from Ethiopia and worked at the nursery. I had talked to him a week earlier about his life; he used to be a farmer.

Now, he was holding a 9-mm automatic — silver, very shiny. He shot the Hispanic man twice in the chest. Then he ran toward the back of the nursery. 

RQ: When I realized what was happening, I crouched down, so I couldn’t see very much. But I heard someone screaming, “He has a gun! He has a gun!” And then I heard more shots. 

BM: I yelled at my wife, “Get out!” Then I ran for the phone at the kiosk desk to call 911. This was before most people had cell phones. But the phone was hooked up to the paging system for the nursery, and I couldn’t get it to work. I turned and ran for the wounded man.

RQ: I got to the victim first. Both lungs had been hit, and I could hear he had sucking chest wounds. He was bleeding out of his mouth, saying, “I’m going to die. I’m going to die.” I told him, “You’re not going to die,” while thinking to myself, He’s going to die. 

BM: I had never met Ron before, but we started working on the patient together. Both of his lungs were collapsing. With sucking chest wounds, the critical issue is to seal up the holes. So normally, you slap a Vaseline dressing on and tape it up real good. But obviously, we didn’t have anything. 

Ron and I took off our shirts and used them to bandage the man’s chest. He wasn’t looking good, starting to turn blue. He was dying. We were yelling for someone to call an ambulance. 

And then suddenly, the shooter was back. He was standing there yelling at us to leave so he could kill the man we were helping. The 9-mil was in his hand, ready to fire. He kept screaming, “I’m not a monkey! I’m not a monkey!”

RQ: The guy was less than 10 feet from us, and we were facing down this gun that looked like a cannon. I thought, This is it. It’s curtains. I’m going to die. We’re all going to die. 

BM: I had decided I would die too. I wasn’t frightened though. It’s hard to explain. Dying was okay because I’d gotten my family away. I just had to stay alive as long as I could in order to provide for the victim. 

It’s what I signed up for when I chose to be a doc — to do whatever was needed. And if I got killed in the process, that was just part of the story. So we started talking to the shooter.

I said, “No, you’re not a monkey. You’re a man, a human being. It’s okay.” We pleaded with him to put the weapon down and not to shoot. We did not leave the patient. Finally, the shooter ran off toward the back of the nursery.

RQ: About 30 seconds after that, we heard two more shots from that direction. 

Then there were sirens, and the place was suddenly crawling with police. The paramedics came and took over. I got up and got out of the way.

BM: A young woman ran up, her mouth covered with blood. She said that there was another victim in the back. I asked a police officer to go with us to check. We started for the back when suddenly, we heard yelling and many rounds being fired. The officer ran in the direction of the shooting. 

The woman and I kept walking through rows of plants and trees. It was like moving through a jungle. Finally, we reached the other victim, an American Indian man, lying on his back. He had a chest wound and a head wound. No respirations. No radial pulse. No carotid pulse. I pronounced him dead.

Then I heard a voice calling for help. There were two women hiding nearby in the bushes. I led them to where the police cars were.

Another officer came over and told me that they had the shooter. The police had shot him in the leg and arrested him.

RQ: The police kept us there for quite some time. Meanwhile, the TV crews arrived. I had a black Toyota 4Runner at the time. My family was home watching the news, and a bulletin came on about a shooting in Midtown. The camera panned around the area, and my wife saw our car on the street! They were all worried until I could call and let them know that I was okay.

BM: As we waited, the sun went down, and I was getting cold. My shirt was a bloody mess. Ron and I just sat there quietly, not saying a whole heck of a lot. 

Finally, an officer took our statements, a detective interviewed us, and they let us leave. I called Beth, and she and the kids came and got me. 

At home, we talked to the kids, letting them express their fears. We put them to bed. I didn’t sleep that night. 

RQ: I can’t describe how weird it was going home with this guy’s blood on my body. Needing to take a bath. Trying to get rid of the stench of what could have been a brutal killing. But it wasn’t. At least, not for our patient. 

Thankfully, there are three hospitals within a stone’s throw of the nursery. The paramedics got the man we helped to Tucson Medical Center and into the OR immediately. Then the general surgeons could get chest tubes in him to reinflate his lungs.

BM: The doctor who treated him called me later. He said that when they put the chest tubes in, they got a liter and a half of blood out of him. If it had taken another 10 minutes or so to get there, he very likely would’ve been dead on arrival in the emergency room. 

RQ: I checked on him at the hospital the next day, and he was doing okay. That was the last time I saw him. 

I only saw the shooter again in court. Dr. Madden and I were both called as witnesses at his trial. He was tried for capital murder and 12 charges of aggravated assault for every person who was at the nursery. He was found guilty on all of them and sentenced to 35 years to life in prison. 

BM: I don’t think the shooter was very well represented in court. It’s not that he didn’t kill one person and critically wound another. He did, and he deserves to be punished for that. But his story wasn’t told.

I knew that during the civil war in Ethiopia, his family had been killed by Cuban soldiers sent there to help the pro-communist government. In a way, I thought of him as two different people: the shooter and the farmer. They are both in prison, but only one of them deserves to be there.

After it happened, I wanted to visit the farmer in the hospital and tell him that, despite what he had done, he was not alone. Our family cared about him. The police wouldn’t let me see him, so I asked the Catholic chaplain of the hospital to go. He gave him my message: that despite all the sorrow and pain, in some distant way, I understood. I respected him as a human being. And I was praying for him.

RQ: It’s safe to say that the experience will affect me forever. For months, even years afterward, if somebody would ask me about what happened, I would start to cry. I would sit in the parking lot of my favorite running trail and worry about the people driving in. If I heard a car backfire, I thought about gunshots. 

It was terrifying. And thank God I’ve never found myself in that position again. But I suspect I’d probably react the same way. This is our calling. It’s what we do — protecting other people and taking care of them.

BM: I’d always wondered what I would do in a situation like this. I knew I could function in a critical care situation, a child in a hospital or in the back of an ambulance. But could I do it when my own life was threatened? I found out that I could, and that was really important to me. 

RQ: It was one of those great lessons in life. You realize how lucky you are and that your life can be snatched away from you in a millisecond. I went to a nursery to buy plants for my yard, and instead I ended up helping to save a life.Bill Madden, MD, is a retired US Army colonel and pediatrician, formerly an associate professor of Clinical Pediatrics at the College of Medicine of the University of Arizona, Tucson. 

Ron Quintia, DDS, is an oral and maxillofacial surgeon at Southern Arizona Oral & Maxillofacial Surgery in Tucson, Arizona. 

A version of this article appeared on Medscape.com .

Emergencies happen anywhere and anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. 'Is There a Doctor in the House?' is a Medscape Medical News series telling these stories.

Bill Madden, MD: It was a Saturday in October of 1996. I had gone to my favorite plant nursery in Tucson with my wife, Beth, and two of my kids, Zach and Katya, who were 9 years old. I went to the back of the nursery to use the bathroom, and I heard two of the workers yelling at each other. The tone was angry. 

I went back up to the front, and Zach said that he was bored. He asked if he could go to the car and get a book, so I gave him my car keys and told him to be careful crossing the street. 

Ron Quintia, DDS: It was late in the afternoon, probably close to 4 PM. I was also at the nursery picking up some plants. 

The noise came out of nowhere. Boom! Boom! Boom! I thought, Wow, that sounds like a gun. But no, it can’t be a gun. This is a plant nursery. 

BM: When I heard the rounds being fired, I knew what that sound meant. I was in the Army for 20 years doing critical care for kids. 

I turned and a young man came running toward me out of the sun. It was hard to see, but I realized a second guy was running about 10 feet behind him. Both men were screaming. 

My wife was about 10 feet away behind a raised planter with Katya. I yelled for them to get down as I dove for the ground.

The first guy, a young Hispanic man, tried to escape through some bushes. But the shooter was catching up. I recognized him. He was from Ethiopia and worked at the nursery. I had talked to him a week earlier about his life; he used to be a farmer.

Now, he was holding a 9-mm automatic — silver, very shiny. He shot the Hispanic man twice in the chest. Then he ran toward the back of the nursery. 

RQ: When I realized what was happening, I crouched down, so I couldn’t see very much. But I heard someone screaming, “He has a gun! He has a gun!” And then I heard more shots. 

BM: I yelled at my wife, “Get out!” Then I ran for the phone at the kiosk desk to call 911. This was before most people had cell phones. But the phone was hooked up to the paging system for the nursery, and I couldn’t get it to work. I turned and ran for the wounded man.

RQ: I got to the victim first. Both lungs had been hit, and I could hear he had sucking chest wounds. He was bleeding out of his mouth, saying, “I’m going to die. I’m going to die.” I told him, “You’re not going to die,” while thinking to myself, He’s going to die. 

BM: I had never met Ron before, but we started working on the patient together. Both of his lungs were collapsing. With sucking chest wounds, the critical issue is to seal up the holes. So normally, you slap a Vaseline dressing on and tape it up real good. But obviously, we didn’t have anything. 

Ron and I took off our shirts and used them to bandage the man’s chest. He wasn’t looking good, starting to turn blue. He was dying. We were yelling for someone to call an ambulance. 

And then suddenly, the shooter was back. He was standing there yelling at us to leave so he could kill the man we were helping. The 9-mil was in his hand, ready to fire. He kept screaming, “I’m not a monkey! I’m not a monkey!”

RQ: The guy was less than 10 feet from us, and we were facing down this gun that looked like a cannon. I thought, This is it. It’s curtains. I’m going to die. We’re all going to die. 

BM: I had decided I would die too. I wasn’t frightened though. It’s hard to explain. Dying was okay because I’d gotten my family away. I just had to stay alive as long as I could in order to provide for the victim. 

It’s what I signed up for when I chose to be a doc — to do whatever was needed. And if I got killed in the process, that was just part of the story. So we started talking to the shooter.

I said, “No, you’re not a monkey. You’re a man, a human being. It’s okay.” We pleaded with him to put the weapon down and not to shoot. We did not leave the patient. Finally, the shooter ran off toward the back of the nursery.

RQ: About 30 seconds after that, we heard two more shots from that direction. 

Then there were sirens, and the place was suddenly crawling with police. The paramedics came and took over. I got up and got out of the way.

BM: A young woman ran up, her mouth covered with blood. She said that there was another victim in the back. I asked a police officer to go with us to check. We started for the back when suddenly, we heard yelling and many rounds being fired. The officer ran in the direction of the shooting. 

The woman and I kept walking through rows of plants and trees. It was like moving through a jungle. Finally, we reached the other victim, an American Indian man, lying on his back. He had a chest wound and a head wound. No respirations. No radial pulse. No carotid pulse. I pronounced him dead.

Then I heard a voice calling for help. There were two women hiding nearby in the bushes. I led them to where the police cars were.

Another officer came over and told me that they had the shooter. The police had shot him in the leg and arrested him.

RQ: The police kept us there for quite some time. Meanwhile, the TV crews arrived. I had a black Toyota 4Runner at the time. My family was home watching the news, and a bulletin came on about a shooting in Midtown. The camera panned around the area, and my wife saw our car on the street! They were all worried until I could call and let them know that I was okay.

BM: As we waited, the sun went down, and I was getting cold. My shirt was a bloody mess. Ron and I just sat there quietly, not saying a whole heck of a lot. 

Finally, an officer took our statements, a detective interviewed us, and they let us leave. I called Beth, and she and the kids came and got me. 

At home, we talked to the kids, letting them express their fears. We put them to bed. I didn’t sleep that night. 

RQ: I can’t describe how weird it was going home with this guy’s blood on my body. Needing to take a bath. Trying to get rid of the stench of what could have been a brutal killing. But it wasn’t. At least, not for our patient. 

Thankfully, there are three hospitals within a stone’s throw of the nursery. The paramedics got the man we helped to Tucson Medical Center and into the OR immediately. Then the general surgeons could get chest tubes in him to reinflate his lungs.

BM: The doctor who treated him called me later. He said that when they put the chest tubes in, they got a liter and a half of blood out of him. If it had taken another 10 minutes or so to get there, he very likely would’ve been dead on arrival in the emergency room. 

RQ: I checked on him at the hospital the next day, and he was doing okay. That was the last time I saw him. 

I only saw the shooter again in court. Dr. Madden and I were both called as witnesses at his trial. He was tried for capital murder and 12 charges of aggravated assault for every person who was at the nursery. He was found guilty on all of them and sentenced to 35 years to life in prison. 

BM: I don’t think the shooter was very well represented in court. It’s not that he didn’t kill one person and critically wound another. He did, and he deserves to be punished for that. But his story wasn’t told.

I knew that during the civil war in Ethiopia, his family had been killed by Cuban soldiers sent there to help the pro-communist government. In a way, I thought of him as two different people: the shooter and the farmer. They are both in prison, but only one of them deserves to be there.

After it happened, I wanted to visit the farmer in the hospital and tell him that, despite what he had done, he was not alone. Our family cared about him. The police wouldn’t let me see him, so I asked the Catholic chaplain of the hospital to go. He gave him my message: that despite all the sorrow and pain, in some distant way, I understood. I respected him as a human being. And I was praying for him.

RQ: It’s safe to say that the experience will affect me forever. For months, even years afterward, if somebody would ask me about what happened, I would start to cry. I would sit in the parking lot of my favorite running trail and worry about the people driving in. If I heard a car backfire, I thought about gunshots. 

It was terrifying. And thank God I’ve never found myself in that position again. But I suspect I’d probably react the same way. This is our calling. It’s what we do — protecting other people and taking care of them.

BM: I’d always wondered what I would do in a situation like this. I knew I could function in a critical care situation, a child in a hospital or in the back of an ambulance. But could I do it when my own life was threatened? I found out that I could, and that was really important to me. 

RQ: It was one of those great lessons in life. You realize how lucky you are and that your life can be snatched away from you in a millisecond. I went to a nursery to buy plants for my yard, and instead I ended up helping to save a life.Bill Madden, MD, is a retired US Army colonel and pediatrician, formerly an associate professor of Clinical Pediatrics at the College of Medicine of the University of Arizona, Tucson. 

Ron Quintia, DDS, is an oral and maxillofacial surgeon at Southern Arizona Oral & Maxillofacial Surgery in Tucson, Arizona. 

A version of this article appeared on Medscape.com .

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

Dry eye and glaucoma may be the two most confounding conditions ophthalmologists face. Late last year, the US Food and Drug Administration (FDA) approved three new treatments for dry eye disease (DED) and one new procedure for glaucoma, which means ophthalmologists will soon have the opportunity to incorporate these therapies into their practices. Meanwhile, several investigative treatments for both chronic ailments will continue to move forward.

Undry Those Eyes

Based on a 2022 study in JAMA Ophthalmology, about 27 million Americans have some form of DED or meibomian gland dysfunction. Treatments aim to preserve and enhance tears and tear production to counteract the grittiness and itchiness that accompany DED.

“For decades, we only had one treatment [cyclosporine] for dry eye, then the second one a few years ago, which is lifitegrast, but nothing innovative until very recently,” Marjan Farid, MD, director of cornea, cataract and refractive surgery at the Gavin Herbert Eye Institute at the University of California-Irvine, told this news organization.

“In 2023, I feel that innovation from the pharmaceutical standpoint in this space really exploded, and it’s very exciting because dry eye disease is such a multifactorial disease that you can’t just go after one angle,” said Dr. Farid, who is also chair of the American Society of Cataract and Refractive Surgery’s cornea clinical committee. “You really need to be able to attack dry eye disease from multiple areas, when the meibomian glands are involved, or whether or not there’s blephartitis.”

The three treatments for DED the FDA approved last year are lotilaner 0.25% ophthalmic solution, which targets the Demodex mites that cause of Demodex blepharitis, a trigger for DED; perfluorohexyloctane ophthalmic solution; and cyclosporine ophthalmic solution 0.1%. The latter two agents coat the ocular surface — perfluorohexyloctane acting as a shield to prevent tear evaporation and cyclosporine 0.1% using perfluorobutylpentane to allow the immunosuppressant cyclosporine to penetrate deeper into the eye.

This year, Dr. Farid said, while ophthalmologists will be adopting those treatments, they’ll also be watching three emerging treatments poised to report results from clinical trial or take other steps toward FDA approval. They include:

• Selenium sulfide 0.5% ophthalmic ointment will move into phase 3 trials. This ointment is applied directly to the lower eyelid to open the meibomian gland (MGs), secretions from which prevent tear evaporation and tear overflow. Results last year from a phase 2 trial demonstrated improvement in MG secretions in treated patients. “It’s a very unique compound because it’s the only compound that could potentially open the meibomian gland orifices along lid margin and improve the quality of secretions,” Dr. Farid said.
• Reproxalap, a reactive aldehyde species (RASP) inhibitor, will be the subject of a new drug application (NDA) resubmission this year. RASPs have been found in elevated levels in ocular and systemic inflammatory disease. The FDA last year notified drug developer Aldeyra Therapeutics that an additional trial was needed to demonstrate efficacy in treating symptoms of DED. Aldeyra said it would resubmit the NDA and report topline trial results in the first half of the year. “That’s a really nice anti-inflammatory eye drop that works early in the inflammatory cascade,” Dr. Farid said. “It acts almost like a steroid does without having the side effects of the steroid.”
• AR-15512, a topical transient receptor potential melastatin 8 agonist, may also be the subject of an NDA this year. Topline results from two phase 3 trials last year demonstrated a clinically meaningful increase in tear production.

The Centers for Disease Control and Prevention estimates 3 million Americans have glaucoma. The use of daily eye drops to lower intraocular pressure (IOP) has been a mainstay of glaucoma therapy treatment for decades. However, a 2018 study put the rates of nonadherence as high at 67%.

In part to skirt the adherence issue, several approaches have evolved to lower IOP without relying on drops. They include laser treatments to perforate the eye’s trabecular meshwork and improve the outflow of aqueous humor, minimally invasive glaucoma surgery to create a small tunnel or even insert a shunt to enable aqueous outflow, and, more recently, implantable depots that release IOP-lowering drugs within the eye over months.

“Glaucoma is a disease that has a slow onset, so you have to diagnose it as early as possible,” Andrew Iwach, MD, a glaucoma specialist in San Francisco and clinical spokesperson for the American Academy of Ophthalmology, told this news organization. “One challenge with glaucoma is its chronic nature. There are different methods that are being looked at to achieve sustained release of drugs — ways you can implant a little bolus of this medicine,” Dr. Iwach added.

Glaucoma also requires regular monitoring of changes in IOP, Iwach noted. “During COVID, there was an increased interest in during this remotely,” he said. A remote monitoring platform, Peripherex, was registered last year with the FDA. It consists of a diagnostic online visual field test that can enable patients with glaucoma to provide data on disease changes from home.

A laser platform, the Belkin Eagle Nd:YAG laser for performing selective laser trabeculoplasty (SLT), in December 2023 received FDA clearance. Dr. Iwach said this is the first innovation in lasers in 20 years in that it eliminates the need for placing a diagnostic lens on the eye itself to direct the laser pulses, a technique called direct SLT. It uses a computer-driven tacking device.

Looking Ahead

A laser in development is ViaLase, which offers femtosecond laser image-guided high-precision trabeculotomy or FLigHT. The VIA-002 study, which began enrolling patients in September 2023, is comparing ViaLase with SLT to determine reduction in unmedicated IOP at 6 and 12 months. A small feasibility study published last year demonstrated safety of the procedure with an average reduction in IOP of 34.6% at 24 months.

Microshunts inserted into the eye also have been used to reduce IOP. An early stage study is evaluating a new-generation, minimally invasive shunt that, once implanted, allows the ophthalmologist to adjust the level of aqueous outflow in an office-based procedure.

Another December 2023 FDA approval was iDose TR, an implant loaded with the prostaglandin analog travoprost 75 mcg. The implant is scheduled for commercial release in the first quarter of 2024, with a projected wholesale acquisition cost of $13,950 per dose or implant.

Two phase 3 trials compared two iDose TR models with two different travoprost release intervals, defined as the fast- and slow-release iDose TR models, respectively, with topical timolol ophthalmic solution, 0.5% twice a day. The trials demonstrated comparable IOP reduction between all three vehicles. At 12 months, 81% of iDose TR subjects required no IOP-lowering topical medications across both trials.

Also in development is an implant that uses a cilioscleral technique to preserve the anterior chamber of the eye, reducing the risk for complications, such as endothelial cell loss or a filtration bleb, that can occur with other implant procedures. Preliminary results of a 12-month study of 57 patients fitted with a new design with the cilioscleral interpositioning device (CID) showed it lowered IOP an average of 13.9 mmHg vs 15.1 mmHg in earlier studies with the device. In the latest study, more than 85% of patients reported being medication free at 12 months. The CID procedure spares the conjunctiva, requiring only a local incision, according to its developers.

As for topical agents that reduce IOP, cannabinoids may soon find their way into the glaucoma specialist’s toolbox. A phase 2 trial evaluating SBI-100 ophthalmic emulsion started enrolling patients late last year. SBI-100 OE is a synthetic prodrug of tetrahydrocannabinol that can bind and activate cannabinoid receptor type 1 in ocular tissues. The trial is scheduled for completion later this year. A phase 1 trial last year demonstrated an average reduction in IOP of 24%.

Another area of focus is on the use of preservatives in topical drops. “One of big issues we’re dealing with is preservatives because you’re marinating these eyes over years with these drops,” Dr. Iwach said. Late last year, the first preservative-free form of latanoprost ophthalmic solution 0.005% launched in the United States. Other delivery systems that remove preservatives from topical drops and preservative-free formulations are in the investigative stage, he said.

Dr. Farid disclosed financial relationships with Alcon Laboratories, Allergan/AbbVie, Bausch + Lomb, Bio-Tissue, CorneaGen, Harrow, Kala Pharmaceuticals, and Tarsus Pharmaceuticals. Dr. Iwach disclosed a previous financial relationship with Belkin Vision as well as relationships with Alcon Laboratories and Innovia.

A version of this article appeared on Medscape.com.

Dry eye and glaucoma may be the two most confounding conditions ophthalmologists face. Late last year, the US Food and Drug Administration (FDA) approved three new treatments for dry eye disease (DED) and one new procedure for glaucoma, which means ophthalmologists will soon have the opportunity to incorporate these therapies into their practices. Meanwhile, several investigative treatments for both chronic ailments will continue to move forward.

Undry Those Eyes

Based on a 2022 study in JAMA Ophthalmology, about 27 million Americans have some form of DED or meibomian gland dysfunction. Treatments aim to preserve and enhance tears and tear production to counteract the grittiness and itchiness that accompany DED.

“For decades, we only had one treatment [cyclosporine] for dry eye, then the second one a few years ago, which is lifitegrast, but nothing innovative until very recently,” Marjan Farid, MD, director of cornea, cataract and refractive surgery at the Gavin Herbert Eye Institute at the University of California-Irvine, told this news organization.

“In 2023, I feel that innovation from the pharmaceutical standpoint in this space really exploded, and it’s very exciting because dry eye disease is such a multifactorial disease that you can’t just go after one angle,” said Dr. Farid, who is also chair of the American Society of Cataract and Refractive Surgery’s cornea clinical committee. “You really need to be able to attack dry eye disease from multiple areas, when the meibomian glands are involved, or whether or not there’s blephartitis.”

The three treatments for DED the FDA approved last year are lotilaner 0.25% ophthalmic solution, which targets the Demodex mites that cause of Demodex blepharitis, a trigger for DED; perfluorohexyloctane ophthalmic solution; and cyclosporine ophthalmic solution 0.1%. The latter two agents coat the ocular surface — perfluorohexyloctane acting as a shield to prevent tear evaporation and cyclosporine 0.1% using perfluorobutylpentane to allow the immunosuppressant cyclosporine to penetrate deeper into the eye.

This year, Dr. Farid said, while ophthalmologists will be adopting those treatments, they’ll also be watching three emerging treatments poised to report results from clinical trial or take other steps toward FDA approval. They include:

• Selenium sulfide 0.5% ophthalmic ointment will move into phase 3 trials. This ointment is applied directly to the lower eyelid to open the meibomian gland (MGs), secretions from which prevent tear evaporation and tear overflow. Results last year from a phase 2 trial demonstrated improvement in MG secretions in treated patients. “It’s a very unique compound because it’s the only compound that could potentially open the meibomian gland orifices along lid margin and improve the quality of secretions,” Dr. Farid said.
• Reproxalap, a reactive aldehyde species (RASP) inhibitor, will be the subject of a new drug application (NDA) resubmission this year. RASPs have been found in elevated levels in ocular and systemic inflammatory disease. The FDA last year notified drug developer Aldeyra Therapeutics that an additional trial was needed to demonstrate efficacy in treating symptoms of DED. Aldeyra said it would resubmit the NDA and report topline trial results in the first half of the year. “That’s a really nice anti-inflammatory eye drop that works early in the inflammatory cascade,” Dr. Farid said. “It acts almost like a steroid does without having the side effects of the steroid.”
• AR-15512, a topical transient receptor potential melastatin 8 agonist, may also be the subject of an NDA this year. Topline results from two phase 3 trials last year demonstrated a clinically meaningful increase in tear production.

The Centers for Disease Control and Prevention estimates 3 million Americans have glaucoma. The use of daily eye drops to lower intraocular pressure (IOP) has been a mainstay of glaucoma therapy treatment for decades. However, a 2018 study put the rates of nonadherence as high at 67%.

In part to skirt the adherence issue, several approaches have evolved to lower IOP without relying on drops. They include laser treatments to perforate the eye’s trabecular meshwork and improve the outflow of aqueous humor, minimally invasive glaucoma surgery to create a small tunnel or even insert a shunt to enable aqueous outflow, and, more recently, implantable depots that release IOP-lowering drugs within the eye over months.

“Glaucoma is a disease that has a slow onset, so you have to diagnose it as early as possible,” Andrew Iwach, MD, a glaucoma specialist in San Francisco and clinical spokesperson for the American Academy of Ophthalmology, told this news organization. “One challenge with glaucoma is its chronic nature. There are different methods that are being looked at to achieve sustained release of drugs — ways you can implant a little bolus of this medicine,” Dr. Iwach added.

Glaucoma also requires regular monitoring of changes in IOP, Iwach noted. “During COVID, there was an increased interest in during this remotely,” he said. A remote monitoring platform, Peripherex, was registered last year with the FDA. It consists of a diagnostic online visual field test that can enable patients with glaucoma to provide data on disease changes from home.

A laser platform, the Belkin Eagle Nd:YAG laser for performing selective laser trabeculoplasty (SLT), in December 2023 received FDA clearance. Dr. Iwach said this is the first innovation in lasers in 20 years in that it eliminates the need for placing a diagnostic lens on the eye itself to direct the laser pulses, a technique called direct SLT. It uses a computer-driven tacking device.

Looking Ahead

A laser in development is ViaLase, which offers femtosecond laser image-guided high-precision trabeculotomy or FLigHT. The VIA-002 study, which began enrolling patients in September 2023, is comparing ViaLase with SLT to determine reduction in unmedicated IOP at 6 and 12 months. A small feasibility study published last year demonstrated safety of the procedure with an average reduction in IOP of 34.6% at 24 months.

Microshunts inserted into the eye also have been used to reduce IOP. An early stage study is evaluating a new-generation, minimally invasive shunt that, once implanted, allows the ophthalmologist to adjust the level of aqueous outflow in an office-based procedure.

Another December 2023 FDA approval was iDose TR, an implant loaded with the prostaglandin analog travoprost 75 mcg. The implant is scheduled for commercial release in the first quarter of 2024, with a projected wholesale acquisition cost of $13,950 per dose or implant.

Two phase 3 trials compared two iDose TR models with two different travoprost release intervals, defined as the fast- and slow-release iDose TR models, respectively, with topical timolol ophthalmic solution, 0.5% twice a day. The trials demonstrated comparable IOP reduction between all three vehicles. At 12 months, 81% of iDose TR subjects required no IOP-lowering topical medications across both trials.

Also in development is an implant that uses a cilioscleral technique to preserve the anterior chamber of the eye, reducing the risk for complications, such as endothelial cell loss or a filtration bleb, that can occur with other implant procedures. Preliminary results of a 12-month study of 57 patients fitted with a new design with the cilioscleral interpositioning device (CID) showed it lowered IOP an average of 13.9 mmHg vs 15.1 mmHg in earlier studies with the device. In the latest study, more than 85% of patients reported being medication free at 12 months. The CID procedure spares the conjunctiva, requiring only a local incision, according to its developers.

As for topical agents that reduce IOP, cannabinoids may soon find their way into the glaucoma specialist’s toolbox. A phase 2 trial evaluating SBI-100 ophthalmic emulsion started enrolling patients late last year. SBI-100 OE is a synthetic prodrug of tetrahydrocannabinol that can bind and activate cannabinoid receptor type 1 in ocular tissues. The trial is scheduled for completion later this year. A phase 1 trial last year demonstrated an average reduction in IOP of 24%.

Another area of focus is on the use of preservatives in topical drops. “One of big issues we’re dealing with is preservatives because you’re marinating these eyes over years with these drops,” Dr. Iwach said. Late last year, the first preservative-free form of latanoprost ophthalmic solution 0.005% launched in the United States. Other delivery systems that remove preservatives from topical drops and preservative-free formulations are in the investigative stage, he said.

Dr. Farid disclosed financial relationships with Alcon Laboratories, Allergan/AbbVie, Bausch + Lomb, Bio-Tissue, CorneaGen, Harrow, Kala Pharmaceuticals, and Tarsus Pharmaceuticals. Dr. Iwach disclosed a previous financial relationship with Belkin Vision as well as relationships with Alcon Laboratories and Innovia.

A version of this article appeared on Medscape.com.

Dry eye and glaucoma may be the two most confounding conditions ophthalmologists face. Late last year, the US Food and Drug Administration (FDA) approved three new treatments for dry eye disease (DED) and one new procedure for glaucoma, which means ophthalmologists will soon have the opportunity to incorporate these therapies into their practices. Meanwhile, several investigative treatments for both chronic ailments will continue to move forward.

Undry Those Eyes

Based on a 2022 study in JAMA Ophthalmology, about 27 million Americans have some form of DED or meibomian gland dysfunction. Treatments aim to preserve and enhance tears and tear production to counteract the grittiness and itchiness that accompany DED.

“For decades, we only had one treatment [cyclosporine] for dry eye, then the second one a few years ago, which is lifitegrast, but nothing innovative until very recently,” Marjan Farid, MD, director of cornea, cataract and refractive surgery at the Gavin Herbert Eye Institute at the University of California-Irvine, told this news organization.

“In 2023, I feel that innovation from the pharmaceutical standpoint in this space really exploded, and it’s very exciting because dry eye disease is such a multifactorial disease that you can’t just go after one angle,” said Dr. Farid, who is also chair of the American Society of Cataract and Refractive Surgery’s cornea clinical committee. “You really need to be able to attack dry eye disease from multiple areas, when the meibomian glands are involved, or whether or not there’s blephartitis.”

The three treatments for DED the FDA approved last year are lotilaner 0.25% ophthalmic solution, which targets the Demodex mites that cause of Demodex blepharitis, a trigger for DED; perfluorohexyloctane ophthalmic solution; and cyclosporine ophthalmic solution 0.1%. The latter two agents coat the ocular surface — perfluorohexyloctane acting as a shield to prevent tear evaporation and cyclosporine 0.1% using perfluorobutylpentane to allow the immunosuppressant cyclosporine to penetrate deeper into the eye.

This year, Dr. Farid said, while ophthalmologists will be adopting those treatments, they’ll also be watching three emerging treatments poised to report results from clinical trial or take other steps toward FDA approval. They include:

• Selenium sulfide 0.5% ophthalmic ointment will move into phase 3 trials. This ointment is applied directly to the lower eyelid to open the meibomian gland (MGs), secretions from which prevent tear evaporation and tear overflow. Results last year from a phase 2 trial demonstrated improvement in MG secretions in treated patients. “It’s a very unique compound because it’s the only compound that could potentially open the meibomian gland orifices along lid margin and improve the quality of secretions,” Dr. Farid said.
• Reproxalap, a reactive aldehyde species (RASP) inhibitor, will be the subject of a new drug application (NDA) resubmission this year. RASPs have been found in elevated levels in ocular and systemic inflammatory disease. The FDA last year notified drug developer Aldeyra Therapeutics that an additional trial was needed to demonstrate efficacy in treating symptoms of DED. Aldeyra said it would resubmit the NDA and report topline trial results in the first half of the year. “That’s a really nice anti-inflammatory eye drop that works early in the inflammatory cascade,” Dr. Farid said. “It acts almost like a steroid does without having the side effects of the steroid.”
• AR-15512, a topical transient receptor potential melastatin 8 agonist, may also be the subject of an NDA this year. Topline results from two phase 3 trials last year demonstrated a clinically meaningful increase in tear production.

The Centers for Disease Control and Prevention estimates 3 million Americans have glaucoma. The use of daily eye drops to lower intraocular pressure (IOP) has been a mainstay of glaucoma therapy treatment for decades. However, a 2018 study put the rates of nonadherence as high at 67%.

In part to skirt the adherence issue, several approaches have evolved to lower IOP without relying on drops. They include laser treatments to perforate the eye’s trabecular meshwork and improve the outflow of aqueous humor, minimally invasive glaucoma surgery to create a small tunnel or even insert a shunt to enable aqueous outflow, and, more recently, implantable depots that release IOP-lowering drugs within the eye over months.

“Glaucoma is a disease that has a slow onset, so you have to diagnose it as early as possible,” Andrew Iwach, MD, a glaucoma specialist in San Francisco and clinical spokesperson for the American Academy of Ophthalmology, told this news organization. “One challenge with glaucoma is its chronic nature. There are different methods that are being looked at to achieve sustained release of drugs — ways you can implant a little bolus of this medicine,” Dr. Iwach added.

Glaucoma also requires regular monitoring of changes in IOP, Iwach noted. “During COVID, there was an increased interest in during this remotely,” he said. A remote monitoring platform, Peripherex, was registered last year with the FDA. It consists of a diagnostic online visual field test that can enable patients with glaucoma to provide data on disease changes from home.

A laser platform, the Belkin Eagle Nd:YAG laser for performing selective laser trabeculoplasty (SLT), in December 2023 received FDA clearance. Dr. Iwach said this is the first innovation in lasers in 20 years in that it eliminates the need for placing a diagnostic lens on the eye itself to direct the laser pulses, a technique called direct SLT. It uses a computer-driven tacking device.

Looking Ahead

A laser in development is ViaLase, which offers femtosecond laser image-guided high-precision trabeculotomy or FLigHT. The VIA-002 study, which began enrolling patients in September 2023, is comparing ViaLase with SLT to determine reduction in unmedicated IOP at 6 and 12 months. A small feasibility study published last year demonstrated safety of the procedure with an average reduction in IOP of 34.6% at 24 months.

Microshunts inserted into the eye also have been used to reduce IOP. An early stage study is evaluating a new-generation, minimally invasive shunt that, once implanted, allows the ophthalmologist to adjust the level of aqueous outflow in an office-based procedure.

Another December 2023 FDA approval was iDose TR, an implant loaded with the prostaglandin analog travoprost 75 mcg. The implant is scheduled for commercial release in the first quarter of 2024, with a projected wholesale acquisition cost of $13,950 per dose or implant.

Two phase 3 trials compared two iDose TR models with two different travoprost release intervals, defined as the fast- and slow-release iDose TR models, respectively, with topical timolol ophthalmic solution, 0.5% twice a day. The trials demonstrated comparable IOP reduction between all three vehicles. At 12 months, 81% of iDose TR subjects required no IOP-lowering topical medications across both trials.

Also in development is an implant that uses a cilioscleral technique to preserve the anterior chamber of the eye, reducing the risk for complications, such as endothelial cell loss or a filtration bleb, that can occur with other implant procedures. Preliminary results of a 12-month study of 57 patients fitted with a new design with the cilioscleral interpositioning device (CID) showed it lowered IOP an average of 13.9 mmHg vs 15.1 mmHg in earlier studies with the device. In the latest study, more than 85% of patients reported being medication free at 12 months. The CID procedure spares the conjunctiva, requiring only a local incision, according to its developers.

As for topical agents that reduce IOP, cannabinoids may soon find their way into the glaucoma specialist’s toolbox. A phase 2 trial evaluating SBI-100 ophthalmic emulsion started enrolling patients late last year. SBI-100 OE is a synthetic prodrug of tetrahydrocannabinol that can bind and activate cannabinoid receptor type 1 in ocular tissues. The trial is scheduled for completion later this year. A phase 1 trial last year demonstrated an average reduction in IOP of 24%.

Another area of focus is on the use of preservatives in topical drops. “One of big issues we’re dealing with is preservatives because you’re marinating these eyes over years with these drops,” Dr. Iwach said. Late last year, the first preservative-free form of latanoprost ophthalmic solution 0.005% launched in the United States. Other delivery systems that remove preservatives from topical drops and preservative-free formulations are in the investigative stage, he said.

Dr. Farid disclosed financial relationships with Alcon Laboratories, Allergan/AbbVie, Bausch + Lomb, Bio-Tissue, CorneaGen, Harrow, Kala Pharmaceuticals, and Tarsus Pharmaceuticals. Dr. Iwach disclosed a previous financial relationship with Belkin Vision as well as relationships with Alcon Laboratories and Innovia.

A version of this article appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be as much as eight times more likely to attempt suicide than are those without the disorder, according to a new study published in the Annals of Internal Medicine on February 5.

The results point to the importance of mental health screening for all patients who may have syndrome, the researchers concluded.

“If we can know such conditions earlier in our clinical practice, we may reduce the subsequence risk and bad consequences,” said Mu-Hong Chen, MD, PhD, an attending psychiatrist at the Department of Psychiatry at Taipei Veterans General Hospital in Taiwan, a coauthor of the study. 

PCOS affects as many as 15% of reproductive-age women in the United States, or approximately six million people. The condition is associated with an increased risk for metabolic disorders, like diabetes and metabolic syndrome, and cardiovascular problems, like hypertension and stroke. The disorder is associated with infertility, weight gain, hirsutism, and skin changes. Evidence also shows that these changes can lead to poorer self-image and mental health conditions like depression and anxiety. 

Dr. Chen and his coauthors compared the records of nearly 19,000 women between ages 12 and 64 years who had a PCOS diagnosis with a matched control group of 189,600 women and girls without PCOS using data from 1997 to 2012 in the Taiwan National Health Insurance Research Database. Cohorts were matched by age, income, urbanization level, and mental health conditions.

The researchers found that the women diagnosed with PCOS were at an 8.47 times higher risk for suicide attempt over the 16-year follow-up period than were women without the condition. Older women with PCOS had slightly lower risk compared with younger women, but the risk was higher compared with older women without PCOS. Studies in other countries have shown similar results.

Adolescents with PCOS had more than five times the risk for attempted suicide than did the control group (hazard ratio [HR], 5.38; 95% CI, 3.93-7.3). Those between ages 20 and 40 years had more than nine times the risk for attempted suicide (HR, 9.15; 95% CI, 8.03-10.42), and those older than 40 years had the lowest risk (HR, 3.75; 95% CI, 2.23-6.28). 

The number of women with PCOS in the study was likely underreported, and those who were included likely had more serious cases, according to Ricardo Azziz, MD, MPH, MBA, professor in the Department of Obstetrics & Gynecology and the Department of Medicine at the University of Alabama at Birmingham. 

The findings, “speak to the fact that women with PCOS do have a greater incidence of mental health disorders and do require clinicians and patients themselves and their families to be aware of these risks,” said Dr. Azziz, former CEO of the American Society for Reproductive Medicine. 

Clinicians should ask their patients with PCOS about suicide risk and mental health, according to Dr. Azziz. 

“It’s not infrequent that those of us in clinical practice see patients who are significantly depressed, and we need to ask the right questions,” he said.

Though he was only aware of a few patients with PCOS who have attempted suicide, he said that clinicians should be prepared to refer these patients to another professional who can address mental health concerns if they express any signs of distress. 

“Simply asking and inviting patients to speak about this will allow physicians to identify patients who may need to be referred,” Dr. Azziz said. 

The study was funded by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology of Taiwan. 

The study authors report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be as much as eight times more likely to attempt suicide than are those without the disorder, according to a new study published in the Annals of Internal Medicine on February 5.

The results point to the importance of mental health screening for all patients who may have syndrome, the researchers concluded.

“If we can know such conditions earlier in our clinical practice, we may reduce the subsequence risk and bad consequences,” said Mu-Hong Chen, MD, PhD, an attending psychiatrist at the Department of Psychiatry at Taipei Veterans General Hospital in Taiwan, a coauthor of the study. 

PCOS affects as many as 15% of reproductive-age women in the United States, or approximately six million people. The condition is associated with an increased risk for metabolic disorders, like diabetes and metabolic syndrome, and cardiovascular problems, like hypertension and stroke. The disorder is associated with infertility, weight gain, hirsutism, and skin changes. Evidence also shows that these changes can lead to poorer self-image and mental health conditions like depression and anxiety. 

Dr. Chen and his coauthors compared the records of nearly 19,000 women between ages 12 and 64 years who had a PCOS diagnosis with a matched control group of 189,600 women and girls without PCOS using data from 1997 to 2012 in the Taiwan National Health Insurance Research Database. Cohorts were matched by age, income, urbanization level, and mental health conditions.

The researchers found that the women diagnosed with PCOS were at an 8.47 times higher risk for suicide attempt over the 16-year follow-up period than were women without the condition. Older women with PCOS had slightly lower risk compared with younger women, but the risk was higher compared with older women without PCOS. Studies in other countries have shown similar results.

Adolescents with PCOS had more than five times the risk for attempted suicide than did the control group (hazard ratio [HR], 5.38; 95% CI, 3.93-7.3). Those between ages 20 and 40 years had more than nine times the risk for attempted suicide (HR, 9.15; 95% CI, 8.03-10.42), and those older than 40 years had the lowest risk (HR, 3.75; 95% CI, 2.23-6.28). 

The number of women with PCOS in the study was likely underreported, and those who were included likely had more serious cases, according to Ricardo Azziz, MD, MPH, MBA, professor in the Department of Obstetrics & Gynecology and the Department of Medicine at the University of Alabama at Birmingham. 

The findings, “speak to the fact that women with PCOS do have a greater incidence of mental health disorders and do require clinicians and patients themselves and their families to be aware of these risks,” said Dr. Azziz, former CEO of the American Society for Reproductive Medicine. 

Clinicians should ask their patients with PCOS about suicide risk and mental health, according to Dr. Azziz. 

“It’s not infrequent that those of us in clinical practice see patients who are significantly depressed, and we need to ask the right questions,” he said.

Though he was only aware of a few patients with PCOS who have attempted suicide, he said that clinicians should be prepared to refer these patients to another professional who can address mental health concerns if they express any signs of distress. 

“Simply asking and inviting patients to speak about this will allow physicians to identify patients who may need to be referred,” Dr. Azziz said. 

The study was funded by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology of Taiwan. 

The study authors report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be as much as eight times more likely to attempt suicide than are those without the disorder, according to a new study published in the Annals of Internal Medicine on February 5.

The results point to the importance of mental health screening for all patients who may have syndrome, the researchers concluded.

“If we can know such conditions earlier in our clinical practice, we may reduce the subsequence risk and bad consequences,” said Mu-Hong Chen, MD, PhD, an attending psychiatrist at the Department of Psychiatry at Taipei Veterans General Hospital in Taiwan, a coauthor of the study. 

PCOS affects as many as 15% of reproductive-age women in the United States, or approximately six million people. The condition is associated with an increased risk for metabolic disorders, like diabetes and metabolic syndrome, and cardiovascular problems, like hypertension and stroke. The disorder is associated with infertility, weight gain, hirsutism, and skin changes. Evidence also shows that these changes can lead to poorer self-image and mental health conditions like depression and anxiety. 

Dr. Chen and his coauthors compared the records of nearly 19,000 women between ages 12 and 64 years who had a PCOS diagnosis with a matched control group of 189,600 women and girls without PCOS using data from 1997 to 2012 in the Taiwan National Health Insurance Research Database. Cohorts were matched by age, income, urbanization level, and mental health conditions.

The researchers found that the women diagnosed with PCOS were at an 8.47 times higher risk for suicide attempt over the 16-year follow-up period than were women without the condition. Older women with PCOS had slightly lower risk compared with younger women, but the risk was higher compared with older women without PCOS. Studies in other countries have shown similar results.

Adolescents with PCOS had more than five times the risk for attempted suicide than did the control group (hazard ratio [HR], 5.38; 95% CI, 3.93-7.3). Those between ages 20 and 40 years had more than nine times the risk for attempted suicide (HR, 9.15; 95% CI, 8.03-10.42), and those older than 40 years had the lowest risk (HR, 3.75; 95% CI, 2.23-6.28). 

The number of women with PCOS in the study was likely underreported, and those who were included likely had more serious cases, according to Ricardo Azziz, MD, MPH, MBA, professor in the Department of Obstetrics & Gynecology and the Department of Medicine at the University of Alabama at Birmingham. 

The findings, “speak to the fact that women with PCOS do have a greater incidence of mental health disorders and do require clinicians and patients themselves and their families to be aware of these risks,” said Dr. Azziz, former CEO of the American Society for Reproductive Medicine. 

Clinicians should ask their patients with PCOS about suicide risk and mental health, according to Dr. Azziz. 

“It’s not infrequent that those of us in clinical practice see patients who are significantly depressed, and we need to ask the right questions,” he said.

Though he was only aware of a few patients with PCOS who have attempted suicide, he said that clinicians should be prepared to refer these patients to another professional who can address mental health concerns if they express any signs of distress. 

“Simply asking and inviting patients to speak about this will allow physicians to identify patients who may need to be referred,” Dr. Azziz said. 

The study was funded by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology of Taiwan. 

The study authors report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Two years after the end of a randomized trial that showed a benefit of daily vitamin D and omega-3 fatty acid (n-3 FA) supplementation for reducing risk for autoimmune diseases, the salubrious effects of daily vitamin D appear to have waned after the supplement was discontinued, while the protection from n-3 lived on for at least 2 additional years.

As previously reported, the randomized VITAL, which was designed primarily to study the effects of vitamin D and n-3 supplementation on incident cancer and cardiovascular disease, also showed that 5 years of vitamin D supplementation was associated with a 22% reduction in risk for confirmed autoimmune diseases, and 5 years of n-3 FA supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases.

Now, investigators Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston, Massachusetts, and colleagues reported that among 21,592 participants in VITAL who agreed to be followed for an additional 2 years after discontinuation, the protection against autoimmune diseases from daily vitamin D (cholecalciferol; 2000 IU/d) was no longer statistically significant, but the benefits of daily marine n-3 FAs (1 g/d as a fish-oil capsule containing 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid) remained significant.

“VITAL observational extension results suggest that vitamin D supplementation should be given on a continuous basis for long-term prevention of [autoimmune diseases]. The beneficial effects of n-3 fatty acids, however, may be prolonged for at least 2 years after discontinuation,” they wrote in an article published in Arthritis & Rheumatology.

Dr. Costenbader told this news organization that the results of the observational extension study suggest that the benefits of vitamin D “wear off more quickly, and it should be continued for a longer period of time or indefinitely, rather than only for 5 years.”

In addition to the disparity in the duration of the protective effect, the investigators also saw differences in the effects across different autoimmune diseases.

“The protective effect of vitamin D seemed strongest for psoriasis, while for omega-3 fatty acids, the protective effects were strongest for rheumatoid arthritis and inflammatory bowel disease,” she said.
 

Mixed Effects

In an interview with this news organization, Janet Funk, MD, MS, vice chair of research in the Department of Medicine and professor in the School of Nutritional Science and Wellness at the University of Arizona, Tucson, Arizona, who was not involved in the study, saidthat the results suggest that while each supplement may offer protection against autoimmune diseases, the effects are inconsistent and may not apply to all patients.

“I think the VITAL extension results suggest that either supplement (or both together) may have benefits in reducing risk of autoimmune diseases, including possible persistent effects posttreatment, but that these effects are nuanced (ie, only in normal weight post-vitamin D treatment) and possibly not uniform across all autoimmune diseases (including possible adverse effects for some — eg, inverse association between prior omega-3 and psoriasis and tendency for increased autoimmune thyroid disease for vitamin D), although the study was not powered sufficiently to draw disease-specific conclusions,” she said.

In an editorial accompanying the study, rheumatologist Joel M. Kremer, MD, of Albany Medical College and the Corrona Research Foundation in Delray Beach, Florida, wrote that “[T]he studies by Dr. Costenbader, et al. have shed new light on the possibility that dietary supplements of n-3 FA [fatty acid] may prevent the onset of [autoimmune disease]. The sustained benefits they describe for as long as 2 years after the supplements are discontinued are consistent with the chronicity of FA species in cellular plasma membranes where they serve as substrates for a diverse array of salient metabolic and inflammatory pathways.”
 

VITAL Then

To test whether vitamin D or marine-derived long-chain n-3 FA supplementation could protect against autoimmune disease over time, Dr. Costenbader and colleagues piggybacked an ancillary study onto the VITAL trial, which had primary outcomes of cancer and cardiovascular disease incidence.

A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older and 13,085 women aged 55 and older. The study had a 2 × 2 factorial design, with patients randomly assigned to vitamin D 2000 IU/d or placebo and then further randomized to either 1 g/d n-3 FAs or placebo in both the vitamin D and placebo primary randomization arms.

In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with a hazard ratio (HR) of 0.68 (P = .02) for incident autoimmune disease, n-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03). However, when probable incident autoimmune disease cases were included, the effect of n-3 became significant, with an HR of 0.82.
 

VITAL Now

In the current analysis, Dr. Costenbader and colleagues reported observational data on 21,592 VITAL participants, a sample representing 83.5% of those who were initially randomized, and 87.9% of those who were alive and could be contacted at the end of the study.

As in the initial trial, the investigators used annual questionnaires to assess incident autoimmune diseases during the randomized follow-up. Participants were asked about new-onset, doctor-diagnosed rheumatoid arthritis, polymyalgia rheumatica, psoriasis, autoimmune thyroid disease, and inflammatory bowel disease. Participants could also write in any other new autoimmune disease diagnoses.

There were 236 new cases of confirmed autoimmune disease that occurred since the initial publication of the trial results, as well as 65 probable cases identified during the median 5.3 years of the randomized portion, and 42 probable cases diagnosed during the 2-year observational phase.

The investigators found that after the 2-year observation period, 255 participants initially randomized to receive vitamin D had a newly developed confirmed autoimmune disease, compared with 259 of those initially randomized to a vitamin D placebo. This translated into a nonsignificant HR of 0.98.

Adding probable autoimmune cases to the confirmed cases made little difference, resulting in a nonsignificant adjusted HR of 0.95.

In contrast, there were 234 confirmed autoimmune disease cases among patients initially assigned to n-3, compared with 280 among patients randomized to the n-3 placebo, translating into a statistically significant HR of 0.83 for new-onset autoimmune disease with n-3.

Dr. Costenbader and colleagues acknowledged that the study was limited by the use of doses intended to prevent cancer or cardiovascular disease and that higher doses intended for high-risk or nutritionally deficient populations might reveal larger effects of supplementation. In addition, they noted the difficulty of identifying the timing and onset of incident disease, and that the small number of cases that occurred during the 2-year observational period precluded detailed analyses of individual autoimmune diseases.

The study was funded by grants from the National Institutes of Health. Dr. Costenbader, Dr. Funk, and Dr. Kremer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Two years after the end of a randomized trial that showed a benefit of daily vitamin D and omega-3 fatty acid (n-3 FA) supplementation for reducing risk for autoimmune diseases, the salubrious effects of daily vitamin D appear to have waned after the supplement was discontinued, while the protection from n-3 lived on for at least 2 additional years.

As previously reported, the randomized VITAL, which was designed primarily to study the effects of vitamin D and n-3 supplementation on incident cancer and cardiovascular disease, also showed that 5 years of vitamin D supplementation was associated with a 22% reduction in risk for confirmed autoimmune diseases, and 5 years of n-3 FA supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases.

Now, investigators Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston, Massachusetts, and colleagues reported that among 21,592 participants in VITAL who agreed to be followed for an additional 2 years after discontinuation, the protection against autoimmune diseases from daily vitamin D (cholecalciferol; 2000 IU/d) was no longer statistically significant, but the benefits of daily marine n-3 FAs (1 g/d as a fish-oil capsule containing 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid) remained significant.

“VITAL observational extension results suggest that vitamin D supplementation should be given on a continuous basis for long-term prevention of [autoimmune diseases]. The beneficial effects of n-3 fatty acids, however, may be prolonged for at least 2 years after discontinuation,” they wrote in an article published in Arthritis & Rheumatology.

Dr. Costenbader told this news organization that the results of the observational extension study suggest that the benefits of vitamin D “wear off more quickly, and it should be continued for a longer period of time or indefinitely, rather than only for 5 years.”

In addition to the disparity in the duration of the protective effect, the investigators also saw differences in the effects across different autoimmune diseases.

“The protective effect of vitamin D seemed strongest for psoriasis, while for omega-3 fatty acids, the protective effects were strongest for rheumatoid arthritis and inflammatory bowel disease,” she said.
 

Mixed Effects

In an interview with this news organization, Janet Funk, MD, MS, vice chair of research in the Department of Medicine and professor in the School of Nutritional Science and Wellness at the University of Arizona, Tucson, Arizona, who was not involved in the study, saidthat the results suggest that while each supplement may offer protection against autoimmune diseases, the effects are inconsistent and may not apply to all patients.

“I think the VITAL extension results suggest that either supplement (or both together) may have benefits in reducing risk of autoimmune diseases, including possible persistent effects posttreatment, but that these effects are nuanced (ie, only in normal weight post-vitamin D treatment) and possibly not uniform across all autoimmune diseases (including possible adverse effects for some — eg, inverse association between prior omega-3 and psoriasis and tendency for increased autoimmune thyroid disease for vitamin D), although the study was not powered sufficiently to draw disease-specific conclusions,” she said.

In an editorial accompanying the study, rheumatologist Joel M. Kremer, MD, of Albany Medical College and the Corrona Research Foundation in Delray Beach, Florida, wrote that “[T]he studies by Dr. Costenbader, et al. have shed new light on the possibility that dietary supplements of n-3 FA [fatty acid] may prevent the onset of [autoimmune disease]. The sustained benefits they describe for as long as 2 years after the supplements are discontinued are consistent with the chronicity of FA species in cellular plasma membranes where they serve as substrates for a diverse array of salient metabolic and inflammatory pathways.”
 

VITAL Then

To test whether vitamin D or marine-derived long-chain n-3 FA supplementation could protect against autoimmune disease over time, Dr. Costenbader and colleagues piggybacked an ancillary study onto the VITAL trial, which had primary outcomes of cancer and cardiovascular disease incidence.

A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older and 13,085 women aged 55 and older. The study had a 2 × 2 factorial design, with patients randomly assigned to vitamin D 2000 IU/d or placebo and then further randomized to either 1 g/d n-3 FAs or placebo in both the vitamin D and placebo primary randomization arms.

In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with a hazard ratio (HR) of 0.68 (P = .02) for incident autoimmune disease, n-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03). However, when probable incident autoimmune disease cases were included, the effect of n-3 became significant, with an HR of 0.82.
 

VITAL Now

In the current analysis, Dr. Costenbader and colleagues reported observational data on 21,592 VITAL participants, a sample representing 83.5% of those who were initially randomized, and 87.9% of those who were alive and could be contacted at the end of the study.

As in the initial trial, the investigators used annual questionnaires to assess incident autoimmune diseases during the randomized follow-up. Participants were asked about new-onset, doctor-diagnosed rheumatoid arthritis, polymyalgia rheumatica, psoriasis, autoimmune thyroid disease, and inflammatory bowel disease. Participants could also write in any other new autoimmune disease diagnoses.

There were 236 new cases of confirmed autoimmune disease that occurred since the initial publication of the trial results, as well as 65 probable cases identified during the median 5.3 years of the randomized portion, and 42 probable cases diagnosed during the 2-year observational phase.

The investigators found that after the 2-year observation period, 255 participants initially randomized to receive vitamin D had a newly developed confirmed autoimmune disease, compared with 259 of those initially randomized to a vitamin D placebo. This translated into a nonsignificant HR of 0.98.

Adding probable autoimmune cases to the confirmed cases made little difference, resulting in a nonsignificant adjusted HR of 0.95.

In contrast, there were 234 confirmed autoimmune disease cases among patients initially assigned to n-3, compared with 280 among patients randomized to the n-3 placebo, translating into a statistically significant HR of 0.83 for new-onset autoimmune disease with n-3.

Dr. Costenbader and colleagues acknowledged that the study was limited by the use of doses intended to prevent cancer or cardiovascular disease and that higher doses intended for high-risk or nutritionally deficient populations might reveal larger effects of supplementation. In addition, they noted the difficulty of identifying the timing and onset of incident disease, and that the small number of cases that occurred during the 2-year observational period precluded detailed analyses of individual autoimmune diseases.

The study was funded by grants from the National Institutes of Health. Dr. Costenbader, Dr. Funk, and Dr. Kremer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Two years after the end of a randomized trial that showed a benefit of daily vitamin D and omega-3 fatty acid (n-3 FA) supplementation for reducing risk for autoimmune diseases, the salubrious effects of daily vitamin D appear to have waned after the supplement was discontinued, while the protection from n-3 lived on for at least 2 additional years.

As previously reported, the randomized VITAL, which was designed primarily to study the effects of vitamin D and n-3 supplementation on incident cancer and cardiovascular disease, also showed that 5 years of vitamin D supplementation was associated with a 22% reduction in risk for confirmed autoimmune diseases, and 5 years of n-3 FA supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases.

Now, investigators Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston, Massachusetts, and colleagues reported that among 21,592 participants in VITAL who agreed to be followed for an additional 2 years after discontinuation, the protection against autoimmune diseases from daily vitamin D (cholecalciferol; 2000 IU/d) was no longer statistically significant, but the benefits of daily marine n-3 FAs (1 g/d as a fish-oil capsule containing 460 mg of eicosapentaenoic acid and 380 mg of docosahexaenoic acid) remained significant.

“VITAL observational extension results suggest that vitamin D supplementation should be given on a continuous basis for long-term prevention of [autoimmune diseases]. The beneficial effects of n-3 fatty acids, however, may be prolonged for at least 2 years after discontinuation,” they wrote in an article published in Arthritis & Rheumatology.

Dr. Costenbader told this news organization that the results of the observational extension study suggest that the benefits of vitamin D “wear off more quickly, and it should be continued for a longer period of time or indefinitely, rather than only for 5 years.”

In addition to the disparity in the duration of the protective effect, the investigators also saw differences in the effects across different autoimmune diseases.

“The protective effect of vitamin D seemed strongest for psoriasis, while for omega-3 fatty acids, the protective effects were strongest for rheumatoid arthritis and inflammatory bowel disease,” she said.
 

Mixed Effects

In an interview with this news organization, Janet Funk, MD, MS, vice chair of research in the Department of Medicine and professor in the School of Nutritional Science and Wellness at the University of Arizona, Tucson, Arizona, who was not involved in the study, saidthat the results suggest that while each supplement may offer protection against autoimmune diseases, the effects are inconsistent and may not apply to all patients.

“I think the VITAL extension results suggest that either supplement (or both together) may have benefits in reducing risk of autoimmune diseases, including possible persistent effects posttreatment, but that these effects are nuanced (ie, only in normal weight post-vitamin D treatment) and possibly not uniform across all autoimmune diseases (including possible adverse effects for some — eg, inverse association between prior omega-3 and psoriasis and tendency for increased autoimmune thyroid disease for vitamin D), although the study was not powered sufficiently to draw disease-specific conclusions,” she said.

In an editorial accompanying the study, rheumatologist Joel M. Kremer, MD, of Albany Medical College and the Corrona Research Foundation in Delray Beach, Florida, wrote that “[T]he studies by Dr. Costenbader, et al. have shed new light on the possibility that dietary supplements of n-3 FA [fatty acid] may prevent the onset of [autoimmune disease]. The sustained benefits they describe for as long as 2 years after the supplements are discontinued are consistent with the chronicity of FA species in cellular plasma membranes where they serve as substrates for a diverse array of salient metabolic and inflammatory pathways.”
 

VITAL Then

To test whether vitamin D or marine-derived long-chain n-3 FA supplementation could protect against autoimmune disease over time, Dr. Costenbader and colleagues piggybacked an ancillary study onto the VITAL trial, which had primary outcomes of cancer and cardiovascular disease incidence.

A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older and 13,085 women aged 55 and older. The study had a 2 × 2 factorial design, with patients randomly assigned to vitamin D 2000 IU/d or placebo and then further randomized to either 1 g/d n-3 FAs or placebo in both the vitamin D and placebo primary randomization arms.

In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with a hazard ratio (HR) of 0.68 (P = .02) for incident autoimmune disease, n-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03). However, when probable incident autoimmune disease cases were included, the effect of n-3 became significant, with an HR of 0.82.
 

VITAL Now

In the current analysis, Dr. Costenbader and colleagues reported observational data on 21,592 VITAL participants, a sample representing 83.5% of those who were initially randomized, and 87.9% of those who were alive and could be contacted at the end of the study.

As in the initial trial, the investigators used annual questionnaires to assess incident autoimmune diseases during the randomized follow-up. Participants were asked about new-onset, doctor-diagnosed rheumatoid arthritis, polymyalgia rheumatica, psoriasis, autoimmune thyroid disease, and inflammatory bowel disease. Participants could also write in any other new autoimmune disease diagnoses.

There were 236 new cases of confirmed autoimmune disease that occurred since the initial publication of the trial results, as well as 65 probable cases identified during the median 5.3 years of the randomized portion, and 42 probable cases diagnosed during the 2-year observational phase.

The investigators found that after the 2-year observation period, 255 participants initially randomized to receive vitamin D had a newly developed confirmed autoimmune disease, compared with 259 of those initially randomized to a vitamin D placebo. This translated into a nonsignificant HR of 0.98.

Adding probable autoimmune cases to the confirmed cases made little difference, resulting in a nonsignificant adjusted HR of 0.95.

In contrast, there were 234 confirmed autoimmune disease cases among patients initially assigned to n-3, compared with 280 among patients randomized to the n-3 placebo, translating into a statistically significant HR of 0.83 for new-onset autoimmune disease with n-3.

Dr. Costenbader and colleagues acknowledged that the study was limited by the use of doses intended to prevent cancer or cardiovascular disease and that higher doses intended for high-risk or nutritionally deficient populations might reveal larger effects of supplementation. In addition, they noted the difficulty of identifying the timing and onset of incident disease, and that the small number of cases that occurred during the 2-year observational period precluded detailed analyses of individual autoimmune diseases.

The study was funded by grants from the National Institutes of Health. Dr. Costenbader, Dr. Funk, and Dr. Kremer reported no relevant financial relationships.

A version of this article appeared on Medscape.com.