Background: Acute kidney injury (AKI) in the ICU is associated with high mortality. It is hypothesized that earlier initiation of RRT may benefit patients by controlling fluid overload and reducing metabolic stress caused by electrolyte and acid-base imbalances. However, prior studies have been conflicting, with the IDEAL-ICU study (2018) demonstrating no improvement in 90-day mortality with early RRT in septic shock.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

Background: Acute kidney injury (AKI) in the ICU is associated with high mortality. It is hypothesized that earlier initiation of RRT may benefit patients by controlling fluid overload and reducing metabolic stress caused by electrolyte and acid-base imbalances. However, prior studies have been conflicting, with the IDEAL-ICU study (2018) demonstrating no improvement in 90-day mortality with early RRT in septic shock.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

Background: Acute kidney injury (AKI) in the ICU is associated with high mortality. It is hypothesized that earlier initiation of RRT may benefit patients by controlling fluid overload and reducing metabolic stress caused by electrolyte and acid-base imbalances. However, prior studies have been conflicting, with the IDEAL-ICU study (2018) demonstrating no improvement in 90-day mortality with early RRT in septic shock.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

LAS VEGAS – In a comparison of data from clinical trials for ulcerative colitis, ozanimod (Zeposia) appeared to be more useful than adalimumab (Humira) and as useful as vedolizumab (Entyvio).

The U.S. Food and Drug Administration approved ozanimod for ulcerative colitis in May of this year, and clinicians are trying to figure out where it fits into the armamentarium, said Marla Dubinsky, MD, professor of pediatrics and medicine in the Division of Pediatric Gastroenterology at Icahn School of Medicine at Mount Sinai, New York.

“It’s an extremely heterogeneous disease,” Dr. Dubinsky told this news organization. “A lot of these indirect comparisons are being done, because these therapies are coming out so quickly.”

No clinical trials have compared either ozanimod to adalimumab or ozanimod to vedolizumab head to head, so Dr. Dubinsky and colleagues pitted the drugs against each other by matching data from individual patients from the True North trial of ozanimod to published data from the ULTRA 1 and 2 trials of adalimumab and the GEMINI 1 trial of vedolizumab.

She presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

From the 1990s until 2014, physicians relied heavily on tumor necrosis factor (TNF) inhibitors, such as adalimumab, to treat ulcerative colitis, Dr. Dubinsky said. Although often effective, these drugs can increase patients’ vulnerability to infections and malignancies.

Approved by the FDA in 2014, vedolizumab works differently: it blocks α4β7 integrin. “The safety profile was extremely favorable,” Dr. Dubinsky said. “That was a revolution, in my opinion.” Still, vedolizumab isn’t always effective, especially for patients who have already received TNF inhibitors without success.

As reported by this news organization, ozanimod works by yet another mechanism: sphingosine l-phosphate receptor modulation.
 

How does ozanimod measure up?

To see how ozanimod stacks up to the two older drugs, Dr. Dubinsky and colleagues weighted the data from True North to match the patient populations in the other trials by age, sex, baseline total Mayo score, disease extent, and prior anti-TNF treatment.

They calculated the odds that ozanimod would produce better clinical and endoscopic responses or be associated with more serious or infectious adverse events in comparison with each of the other drugs. The comparisons included both the induction and maintenance phases of the trials.

The researchers compared ozanimod to adalimumab for patients who were anti-TNF naive. They found that the patients who took ozanimod were more likely to experience a clinical response than those who took adalimumab (odds ratio, 1.68; 95% CI, 1.03-2.74). The patients who took ozanimod were also more likely to have endoscopic improvement (OR, 2.73; 95% CI, 1.44-5.17).

They found that the patients who had received a TNF inhibitor were also more likely to experience a clinical response with ozanimod than with adalimumab (OR, 2.53; 95% CI, 1.13-5.67).

In both the induction and the maintenance phases, the other differences in efficacy between ozanimod and adalimumab did not reach statistical significance.

As for safety, in the induction phases of the trials, the researchers found that 11.3% of patients who received ozanimod had infections, compared to 20.2% of those taking adalimumab, which was statistically significant (P < .01). Other differences in safety were not statistically significant.

With regard to vedolizumab, Dr. Dubinsky and colleagues found no statistically significant differences between it and ozanimod in the induction phases.

In the maintenance phases, among patients who were anti-TNF naive, the odds of clinical response were lower with ozanimod than with vedolizumab (OR, 0.40; 95% CI, 0.21-0.76). The odds of endoscopic improvement were very nearly lower (OR, 0.52; 95% CI, 0.27-1.01). The researchers attributed these findings to a higher placebo response in the True North trial (the ozanimod trial) than in GEMINI 1 (the vedolizumab trial).

There were no other significant differences in efficacy between ozanimod and vedolizumab, either in the cohort that had received a TNF inhibitor or in the cohort that had not.

As for safety, there were also no statistically significant differences between vedolizumab and ozanimod in the induction phases. During the maintenance phases, 71.3% of patients who received vedolizumab had infections, compared to 25.0% in the matched cohort of patients who received ozanimod, which was a statistically significant difference (P < .001). The other differences in this phase were not significant.

Dr. Dubinsky acknowledged that the results were not as reliable as would have been the case in a prospective, head-to-head comparison, because the researchers could not be sure that they had fully adjusted for the differences in the populations and the designs of the studies.

“In TNF-inhibitor–naive patients, I could use vedolizumab or ozanimod,” Dr. Dubinsky said. But these are not the only options, she said. She said that “in TNF failure, I would use ustekinumab or even tofacitinib.” Ustekinumab (Stelara) is a human interleukin-12 and -23 antagonist; tofacitinib (Xeljanz) is a Janus kinase inhibitor.

The study’s limitations are significant, said session moderator Jonathan Leighton, MD, a professor of medicine at the Mayo Clinic in Phoenix, Arizona, “but it certainly shows that ozanimod had a positive profile compared to adalimumab and has overall comparable benefits with vedolizumab,” he said in an interview.

Dr. Leighton added that someday researchers may find biomarkers that will identify the best drug for each patient. In the meantime, clinicians are often left choosing therapies on the basis of such factors as which route of administration the patients prefer, he said. Vedolizumab is given by intravenous infusion, ozanimod is taken orally, and adalimumab is given by subcutaneous injection.

The study was funded by Bristol-Myers Squibb. Dr. Leighton has financial relationships with Olympus and Pfizer. Dr. Dubinsky has relationships with all or most of the companies that make drugs for inflammatory bowel disease.

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

LAS VEGAS – In a comparison of data from clinical trials for ulcerative colitis, ozanimod (Zeposia) appeared to be more useful than adalimumab (Humira) and as useful as vedolizumab (Entyvio).

The U.S. Food and Drug Administration approved ozanimod for ulcerative colitis in May of this year, and clinicians are trying to figure out where it fits into the armamentarium, said Marla Dubinsky, MD, professor of pediatrics and medicine in the Division of Pediatric Gastroenterology at Icahn School of Medicine at Mount Sinai, New York.

“It’s an extremely heterogeneous disease,” Dr. Dubinsky told this news organization. “A lot of these indirect comparisons are being done, because these therapies are coming out so quickly.”

No clinical trials have compared either ozanimod to adalimumab or ozanimod to vedolizumab head to head, so Dr. Dubinsky and colleagues pitted the drugs against each other by matching data from individual patients from the True North trial of ozanimod to published data from the ULTRA 1 and 2 trials of adalimumab and the GEMINI 1 trial of vedolizumab.

She presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

From the 1990s until 2014, physicians relied heavily on tumor necrosis factor (TNF) inhibitors, such as adalimumab, to treat ulcerative colitis, Dr. Dubinsky said. Although often effective, these drugs can increase patients’ vulnerability to infections and malignancies.

Approved by the FDA in 2014, vedolizumab works differently: it blocks α4β7 integrin. “The safety profile was extremely favorable,” Dr. Dubinsky said. “That was a revolution, in my opinion.” Still, vedolizumab isn’t always effective, especially for patients who have already received TNF inhibitors without success.

As reported by this news organization, ozanimod works by yet another mechanism: sphingosine l-phosphate receptor modulation.
 

How does ozanimod measure up?

To see how ozanimod stacks up to the two older drugs, Dr. Dubinsky and colleagues weighted the data from True North to match the patient populations in the other trials by age, sex, baseline total Mayo score, disease extent, and prior anti-TNF treatment.

They calculated the odds that ozanimod would produce better clinical and endoscopic responses or be associated with more serious or infectious adverse events in comparison with each of the other drugs. The comparisons included both the induction and maintenance phases of the trials.

The researchers compared ozanimod to adalimumab for patients who were anti-TNF naive. They found that the patients who took ozanimod were more likely to experience a clinical response than those who took adalimumab (odds ratio, 1.68; 95% CI, 1.03-2.74). The patients who took ozanimod were also more likely to have endoscopic improvement (OR, 2.73; 95% CI, 1.44-5.17).

They found that the patients who had received a TNF inhibitor were also more likely to experience a clinical response with ozanimod than with adalimumab (OR, 2.53; 95% CI, 1.13-5.67).

In both the induction and the maintenance phases, the other differences in efficacy between ozanimod and adalimumab did not reach statistical significance.

As for safety, in the induction phases of the trials, the researchers found that 11.3% of patients who received ozanimod had infections, compared to 20.2% of those taking adalimumab, which was statistically significant (P < .01). Other differences in safety were not statistically significant.

With regard to vedolizumab, Dr. Dubinsky and colleagues found no statistically significant differences between it and ozanimod in the induction phases.

In the maintenance phases, among patients who were anti-TNF naive, the odds of clinical response were lower with ozanimod than with vedolizumab (OR, 0.40; 95% CI, 0.21-0.76). The odds of endoscopic improvement were very nearly lower (OR, 0.52; 95% CI, 0.27-1.01). The researchers attributed these findings to a higher placebo response in the True North trial (the ozanimod trial) than in GEMINI 1 (the vedolizumab trial).

There were no other significant differences in efficacy between ozanimod and vedolizumab, either in the cohort that had received a TNF inhibitor or in the cohort that had not.

As for safety, there were also no statistically significant differences between vedolizumab and ozanimod in the induction phases. During the maintenance phases, 71.3% of patients who received vedolizumab had infections, compared to 25.0% in the matched cohort of patients who received ozanimod, which was a statistically significant difference (P < .001). The other differences in this phase were not significant.

Dr. Dubinsky acknowledged that the results were not as reliable as would have been the case in a prospective, head-to-head comparison, because the researchers could not be sure that they had fully adjusted for the differences in the populations and the designs of the studies.

“In TNF-inhibitor–naive patients, I could use vedolizumab or ozanimod,” Dr. Dubinsky said. But these are not the only options, she said. She said that “in TNF failure, I would use ustekinumab or even tofacitinib.” Ustekinumab (Stelara) is a human interleukin-12 and -23 antagonist; tofacitinib (Xeljanz) is a Janus kinase inhibitor.

The study’s limitations are significant, said session moderator Jonathan Leighton, MD, a professor of medicine at the Mayo Clinic in Phoenix, Arizona, “but it certainly shows that ozanimod had a positive profile compared to adalimumab and has overall comparable benefits with vedolizumab,” he said in an interview.

Dr. Leighton added that someday researchers may find biomarkers that will identify the best drug for each patient. In the meantime, clinicians are often left choosing therapies on the basis of such factors as which route of administration the patients prefer, he said. Vedolizumab is given by intravenous infusion, ozanimod is taken orally, and adalimumab is given by subcutaneous injection.

The study was funded by Bristol-Myers Squibb. Dr. Leighton has financial relationships with Olympus and Pfizer. Dr. Dubinsky has relationships with all or most of the companies that make drugs for inflammatory bowel disease.

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

LAS VEGAS – In a comparison of data from clinical trials for ulcerative colitis, ozanimod (Zeposia) appeared to be more useful than adalimumab (Humira) and as useful as vedolizumab (Entyvio).

The U.S. Food and Drug Administration approved ozanimod for ulcerative colitis in May of this year, and clinicians are trying to figure out where it fits into the armamentarium, said Marla Dubinsky, MD, professor of pediatrics and medicine in the Division of Pediatric Gastroenterology at Icahn School of Medicine at Mount Sinai, New York.

“It’s an extremely heterogeneous disease,” Dr. Dubinsky told this news organization. “A lot of these indirect comparisons are being done, because these therapies are coming out so quickly.”

No clinical trials have compared either ozanimod to adalimumab or ozanimod to vedolizumab head to head, so Dr. Dubinsky and colleagues pitted the drugs against each other by matching data from individual patients from the True North trial of ozanimod to published data from the ULTRA 1 and 2 trials of adalimumab and the GEMINI 1 trial of vedolizumab.

She presented the findings here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

From the 1990s until 2014, physicians relied heavily on tumor necrosis factor (TNF) inhibitors, such as adalimumab, to treat ulcerative colitis, Dr. Dubinsky said. Although often effective, these drugs can increase patients’ vulnerability to infections and malignancies.

Approved by the FDA in 2014, vedolizumab works differently: it blocks α4β7 integrin. “The safety profile was extremely favorable,” Dr. Dubinsky said. “That was a revolution, in my opinion.” Still, vedolizumab isn’t always effective, especially for patients who have already received TNF inhibitors without success.

As reported by this news organization, ozanimod works by yet another mechanism: sphingosine l-phosphate receptor modulation.
 

How does ozanimod measure up?

To see how ozanimod stacks up to the two older drugs, Dr. Dubinsky and colleagues weighted the data from True North to match the patient populations in the other trials by age, sex, baseline total Mayo score, disease extent, and prior anti-TNF treatment.

They calculated the odds that ozanimod would produce better clinical and endoscopic responses or be associated with more serious or infectious adverse events in comparison with each of the other drugs. The comparisons included both the induction and maintenance phases of the trials.

The researchers compared ozanimod to adalimumab for patients who were anti-TNF naive. They found that the patients who took ozanimod were more likely to experience a clinical response than those who took adalimumab (odds ratio, 1.68; 95% CI, 1.03-2.74). The patients who took ozanimod were also more likely to have endoscopic improvement (OR, 2.73; 95% CI, 1.44-5.17).

They found that the patients who had received a TNF inhibitor were also more likely to experience a clinical response with ozanimod than with adalimumab (OR, 2.53; 95% CI, 1.13-5.67).

In both the induction and the maintenance phases, the other differences in efficacy between ozanimod and adalimumab did not reach statistical significance.

As for safety, in the induction phases of the trials, the researchers found that 11.3% of patients who received ozanimod had infections, compared to 20.2% of those taking adalimumab, which was statistically significant (P < .01). Other differences in safety were not statistically significant.

With regard to vedolizumab, Dr. Dubinsky and colleagues found no statistically significant differences between it and ozanimod in the induction phases.

In the maintenance phases, among patients who were anti-TNF naive, the odds of clinical response were lower with ozanimod than with vedolizumab (OR, 0.40; 95% CI, 0.21-0.76). The odds of endoscopic improvement were very nearly lower (OR, 0.52; 95% CI, 0.27-1.01). The researchers attributed these findings to a higher placebo response in the True North trial (the ozanimod trial) than in GEMINI 1 (the vedolizumab trial).

There were no other significant differences in efficacy between ozanimod and vedolizumab, either in the cohort that had received a TNF inhibitor or in the cohort that had not.

As for safety, there were also no statistically significant differences between vedolizumab and ozanimod in the induction phases. During the maintenance phases, 71.3% of patients who received vedolizumab had infections, compared to 25.0% in the matched cohort of patients who received ozanimod, which was a statistically significant difference (P < .001). The other differences in this phase were not significant.

Dr. Dubinsky acknowledged that the results were not as reliable as would have been the case in a prospective, head-to-head comparison, because the researchers could not be sure that they had fully adjusted for the differences in the populations and the designs of the studies.

“In TNF-inhibitor–naive patients, I could use vedolizumab or ozanimod,” Dr. Dubinsky said. But these are not the only options, she said. She said that “in TNF failure, I would use ustekinumab or even tofacitinib.” Ustekinumab (Stelara) is a human interleukin-12 and -23 antagonist; tofacitinib (Xeljanz) is a Janus kinase inhibitor.

The study’s limitations are significant, said session moderator Jonathan Leighton, MD, a professor of medicine at the Mayo Clinic in Phoenix, Arizona, “but it certainly shows that ozanimod had a positive profile compared to adalimumab and has overall comparable benefits with vedolizumab,” he said in an interview.

Dr. Leighton added that someday researchers may find biomarkers that will identify the best drug for each patient. In the meantime, clinicians are often left choosing therapies on the basis of such factors as which route of administration the patients prefer, he said. Vedolizumab is given by intravenous infusion, ozanimod is taken orally, and adalimumab is given by subcutaneous injection.

The study was funded by Bristol-Myers Squibb. Dr. Leighton has financial relationships with Olympus and Pfizer. Dr. Dubinsky has relationships with all or most of the companies that make drugs for inflammatory bowel disease.

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

My journey to becoming a family medicine physician wasn’t a linear path. However, that nonlinear path is what has led me to love this field of medicine and the connections I make with patients, while also continuing to hope for improvements within the systems that we utilize to provide care for patients.

I became interested in becoming a physician during my very last semester of college. I volunteered in a hospital psychiatric department in the unit that provided electroconvulsive therapy to patients with severe mental health diagnoses. Although this was about 15 years ago, I still vividly remember the curiosity I had walking around the hospital looking around at all the doctors and nurses and wanting to understand what their day-to-day life was like helping people to optimize their health.

Up until that time, thankfully my family and I had been relatively healthy, and, outside of routine checkups, my time spent in a hospital or clinic was limited. Therefore, those months of volunteering at the hospital were the longest periods of time I’d spent around physicians and other health care professionals really witnessing firsthand the science and the art of medicine.

During my time volunteering I saw one patient over the course of several weeks who was catatonic when I first met her, but by the end of several electroconvulsive therapy treatments she had a subtle smile on her face and we were able to have a conversation. She was a younger Black woman like myself and at that moment I knew that I wanted to become a physician and be involved in people’s lives in such a unique manner.

I worked for several years before applying to medical school. During that time two of my jobs involved doing home visits with children, young adults, and their families. I once again experienced the connection that one can make with someone and their family over a short period of time when you actively listen, understand what is important to them, and work together.

After several years of this work I got accepted into medical school and excitedly started the path to becoming a physician. While the learning curve was difficult, I genuinely enjoyed every block of medical school, including learning the anatomy, pathophysiology, and pharmacology. I could not wait to be in front of patients to use this newfound knowledge to help solve their health problems.
 

‘There is no such thing as a single issue-struggle’

As I started the third year of medical school and clinical rotations, I found joy in being in hospitals and clinics. I also came to recognize that understanding the pharmacology of why metformin helps improve the hemoglobin A1c in people with diabetes is not necessarily one of the keys to helping people optimize their health. I started to talk with patients and all sorts of questions would come to mind. Where did they grow up? What did they identify as their culture? What did they do in their day to day? Did they have a home and support at that home? Are they someone’s caretaker? What are their hopes for the future? And the list goes on.

I ultimately chose family medicine as a specialty because, as Audre Lorde said, “there is no such thing as a single-issue struggle because we do not live single-issue lives,” and family medicine allows one to look at the intersections of people’s lives and how they affect their health and well-being.

I currently practice as a family medicine physician in a setting in which I provide a lot of sexual and reproductive health care. I welcome patients of all ages and genders, and this care includes preconception counseling, contraceptive counseling, prenatal and postpartum care, STI testing and treatment, abortion care, and routine preventive care – just to name a few.

I decided to specialize in sexual and reproductive health care within family medicine because of the historic discrimination and inequitable treatment that is often experienced by young Black persons when they seek care for their sexual health and/or reproductive choices. In addition, there is often stigma within communities when it comes to talking about sex, bodies, and pleasure.

Recently, after a few minutes with a patient, she shared with me that she just completed nursing school and was studying for her exams. We talked about what type of jobs she was looking to apply for and where she wanted to work. I expressed to her that I was proud of the hard work she put in to complete nursing school and commiserated with her about the challenges in schooling and studying that it takes to start in the health care field. The conversation eventually found its way to talking about her sexual and reproductive health care. She shared with me that she was interested in having a child; however, at this time she put those plans on hold because she was scared about the racism within health care and the unacceptable high rates of maternal mortality among Black women in this country.

I listened and shared that as someone who also identifies as a Black woman, I have similar fears and anxieties surrounding my own reproductive health future. During the visit with this patient, I used my training in family medicine to better understand her physical and mental health needs and reassured her that I was going to partner with her through her health care journey.
 

Hope for the future of family medicine

As I work on a day-to-day basis I often think about my hopes for patients, as well as my hopes for medicine and the field of family medicine. My hope for the future of family medicine is that we can continue to make meaningful connections with patients to help them optimize their health and well-being.

I imagine a system in which we have the time and support to do this for all of our patients regardless of their immigration status, socioeconomic status, or any other historically excluded status. My hope for the future of family medicine is that I can write a prescription for a medication or physical therapy, and the patient is able to fill the prescription without having to worry about the financial implications of paying for it. My hope for the future of family medicine is that patients can seek out care without the fear of discrimination or racism through an increasingly diverse work force. My hope for the future of family medicine is that these improvements become a reality and that as physicians we can appreciate the connections we make with patients and the impact this has on their overall health and well-being.
 

Dr. Lockley is a family medicine physician currently living in Harlem, N.Y., and a member of the editorial advisory board of Family Practice News. She currently works for Public Health Solutions’ Sexual and Reproductive Health Centers in Brooklyn, providing primary care and reproductive health care services there, and as an abortion provider throughout the New York region. She completed both medical school and residency in Philadelphia and then did a fellowship in reproductive health care and advocacy through the Family Health Center of Harlem and the Reproductive Health Access Project. She can be reached at [email protected].

My journey to becoming a family medicine physician wasn’t a linear path. However, that nonlinear path is what has led me to love this field of medicine and the connections I make with patients, while also continuing to hope for improvements within the systems that we utilize to provide care for patients.

I became interested in becoming a physician during my very last semester of college. I volunteered in a hospital psychiatric department in the unit that provided electroconvulsive therapy to patients with severe mental health diagnoses. Although this was about 15 years ago, I still vividly remember the curiosity I had walking around the hospital looking around at all the doctors and nurses and wanting to understand what their day-to-day life was like helping people to optimize their health.

Up until that time, thankfully my family and I had been relatively healthy, and, outside of routine checkups, my time spent in a hospital or clinic was limited. Therefore, those months of volunteering at the hospital were the longest periods of time I’d spent around physicians and other health care professionals really witnessing firsthand the science and the art of medicine.

During my time volunteering I saw one patient over the course of several weeks who was catatonic when I first met her, but by the end of several electroconvulsive therapy treatments she had a subtle smile on her face and we were able to have a conversation. She was a younger Black woman like myself and at that moment I knew that I wanted to become a physician and be involved in people’s lives in such a unique manner.

I worked for several years before applying to medical school. During that time two of my jobs involved doing home visits with children, young adults, and their families. I once again experienced the connection that one can make with someone and their family over a short period of time when you actively listen, understand what is important to them, and work together.

After several years of this work I got accepted into medical school and excitedly started the path to becoming a physician. While the learning curve was difficult, I genuinely enjoyed every block of medical school, including learning the anatomy, pathophysiology, and pharmacology. I could not wait to be in front of patients to use this newfound knowledge to help solve their health problems.
 

‘There is no such thing as a single issue-struggle’

As I started the third year of medical school and clinical rotations, I found joy in being in hospitals and clinics. I also came to recognize that understanding the pharmacology of why metformin helps improve the hemoglobin A1c in people with diabetes is not necessarily one of the keys to helping people optimize their health. I started to talk with patients and all sorts of questions would come to mind. Where did they grow up? What did they identify as their culture? What did they do in their day to day? Did they have a home and support at that home? Are they someone’s caretaker? What are their hopes for the future? And the list goes on.

I ultimately chose family medicine as a specialty because, as Audre Lorde said, “there is no such thing as a single-issue struggle because we do not live single-issue lives,” and family medicine allows one to look at the intersections of people’s lives and how they affect their health and well-being.

I currently practice as a family medicine physician in a setting in which I provide a lot of sexual and reproductive health care. I welcome patients of all ages and genders, and this care includes preconception counseling, contraceptive counseling, prenatal and postpartum care, STI testing and treatment, abortion care, and routine preventive care – just to name a few.

I decided to specialize in sexual and reproductive health care within family medicine because of the historic discrimination and inequitable treatment that is often experienced by young Black persons when they seek care for their sexual health and/or reproductive choices. In addition, there is often stigma within communities when it comes to talking about sex, bodies, and pleasure.

Recently, after a few minutes with a patient, she shared with me that she just completed nursing school and was studying for her exams. We talked about what type of jobs she was looking to apply for and where she wanted to work. I expressed to her that I was proud of the hard work she put in to complete nursing school and commiserated with her about the challenges in schooling and studying that it takes to start in the health care field. The conversation eventually found its way to talking about her sexual and reproductive health care. She shared with me that she was interested in having a child; however, at this time she put those plans on hold because she was scared about the racism within health care and the unacceptable high rates of maternal mortality among Black women in this country.

I listened and shared that as someone who also identifies as a Black woman, I have similar fears and anxieties surrounding my own reproductive health future. During the visit with this patient, I used my training in family medicine to better understand her physical and mental health needs and reassured her that I was going to partner with her through her health care journey.
 

Hope for the future of family medicine

As I work on a day-to-day basis I often think about my hopes for patients, as well as my hopes for medicine and the field of family medicine. My hope for the future of family medicine is that we can continue to make meaningful connections with patients to help them optimize their health and well-being.

I imagine a system in which we have the time and support to do this for all of our patients regardless of their immigration status, socioeconomic status, or any other historically excluded status. My hope for the future of family medicine is that I can write a prescription for a medication or physical therapy, and the patient is able to fill the prescription without having to worry about the financial implications of paying for it. My hope for the future of family medicine is that patients can seek out care without the fear of discrimination or racism through an increasingly diverse work force. My hope for the future of family medicine is that these improvements become a reality and that as physicians we can appreciate the connections we make with patients and the impact this has on their overall health and well-being.
 

Dr. Lockley is a family medicine physician currently living in Harlem, N.Y., and a member of the editorial advisory board of Family Practice News. She currently works for Public Health Solutions’ Sexual and Reproductive Health Centers in Brooklyn, providing primary care and reproductive health care services there, and as an abortion provider throughout the New York region. She completed both medical school and residency in Philadelphia and then did a fellowship in reproductive health care and advocacy through the Family Health Center of Harlem and the Reproductive Health Access Project. She can be reached at [email protected].

My journey to becoming a family medicine physician wasn’t a linear path. However, that nonlinear path is what has led me to love this field of medicine and the connections I make with patients, while also continuing to hope for improvements within the systems that we utilize to provide care for patients.

I became interested in becoming a physician during my very last semester of college. I volunteered in a hospital psychiatric department in the unit that provided electroconvulsive therapy to patients with severe mental health diagnoses. Although this was about 15 years ago, I still vividly remember the curiosity I had walking around the hospital looking around at all the doctors and nurses and wanting to understand what their day-to-day life was like helping people to optimize their health.

Up until that time, thankfully my family and I had been relatively healthy, and, outside of routine checkups, my time spent in a hospital or clinic was limited. Therefore, those months of volunteering at the hospital were the longest periods of time I’d spent around physicians and other health care professionals really witnessing firsthand the science and the art of medicine.

During my time volunteering I saw one patient over the course of several weeks who was catatonic when I first met her, but by the end of several electroconvulsive therapy treatments she had a subtle smile on her face and we were able to have a conversation. She was a younger Black woman like myself and at that moment I knew that I wanted to become a physician and be involved in people’s lives in such a unique manner.

I worked for several years before applying to medical school. During that time two of my jobs involved doing home visits with children, young adults, and their families. I once again experienced the connection that one can make with someone and their family over a short period of time when you actively listen, understand what is important to them, and work together.

After several years of this work I got accepted into medical school and excitedly started the path to becoming a physician. While the learning curve was difficult, I genuinely enjoyed every block of medical school, including learning the anatomy, pathophysiology, and pharmacology. I could not wait to be in front of patients to use this newfound knowledge to help solve their health problems.
 

‘There is no such thing as a single issue-struggle’

As I started the third year of medical school and clinical rotations, I found joy in being in hospitals and clinics. I also came to recognize that understanding the pharmacology of why metformin helps improve the hemoglobin A1c in people with diabetes is not necessarily one of the keys to helping people optimize their health. I started to talk with patients and all sorts of questions would come to mind. Where did they grow up? What did they identify as their culture? What did they do in their day to day? Did they have a home and support at that home? Are they someone’s caretaker? What are their hopes for the future? And the list goes on.

I ultimately chose family medicine as a specialty because, as Audre Lorde said, “there is no such thing as a single-issue struggle because we do not live single-issue lives,” and family medicine allows one to look at the intersections of people’s lives and how they affect their health and well-being.

I currently practice as a family medicine physician in a setting in which I provide a lot of sexual and reproductive health care. I welcome patients of all ages and genders, and this care includes preconception counseling, contraceptive counseling, prenatal and postpartum care, STI testing and treatment, abortion care, and routine preventive care – just to name a few.

I decided to specialize in sexual and reproductive health care within family medicine because of the historic discrimination and inequitable treatment that is often experienced by young Black persons when they seek care for their sexual health and/or reproductive choices. In addition, there is often stigma within communities when it comes to talking about sex, bodies, and pleasure.

Recently, after a few minutes with a patient, she shared with me that she just completed nursing school and was studying for her exams. We talked about what type of jobs she was looking to apply for and where she wanted to work. I expressed to her that I was proud of the hard work she put in to complete nursing school and commiserated with her about the challenges in schooling and studying that it takes to start in the health care field. The conversation eventually found its way to talking about her sexual and reproductive health care. She shared with me that she was interested in having a child; however, at this time she put those plans on hold because she was scared about the racism within health care and the unacceptable high rates of maternal mortality among Black women in this country.

I listened and shared that as someone who also identifies as a Black woman, I have similar fears and anxieties surrounding my own reproductive health future. During the visit with this patient, I used my training in family medicine to better understand her physical and mental health needs and reassured her that I was going to partner with her through her health care journey.
 

Hope for the future of family medicine

As I work on a day-to-day basis I often think about my hopes for patients, as well as my hopes for medicine and the field of family medicine. My hope for the future of family medicine is that we can continue to make meaningful connections with patients to help them optimize their health and well-being.

I imagine a system in which we have the time and support to do this for all of our patients regardless of their immigration status, socioeconomic status, or any other historically excluded status. My hope for the future of family medicine is that I can write a prescription for a medication or physical therapy, and the patient is able to fill the prescription without having to worry about the financial implications of paying for it. My hope for the future of family medicine is that patients can seek out care without the fear of discrimination or racism through an increasingly diverse work force. My hope for the future of family medicine is that these improvements become a reality and that as physicians we can appreciate the connections we make with patients and the impact this has on their overall health and well-being.
 

Dr. Lockley is a family medicine physician currently living in Harlem, N.Y., and a member of the editorial advisory board of Family Practice News. She currently works for Public Health Solutions’ Sexual and Reproductive Health Centers in Brooklyn, providing primary care and reproductive health care services there, and as an abortion provider throughout the New York region. She completed both medical school and residency in Philadelphia and then did a fellowship in reproductive health care and advocacy through the Family Health Center of Harlem and the Reproductive Health Access Project. She can be reached at [email protected].

A newly published study that compared the accuracy of two commonly used lung cancer screening algorithms found that the American College of Radiology Lung-RADs screening tool is more accurate in detecting cancerous nodules in patients with a history of lung cancer than NELSON, a Dutch clinical trial that measures nodule volume and growth rate instead of linear measurement of nodule size as done in Lung-RADs.

The study, published in the American Journal of Roentgenology on Nov. 10, 2021,was a retrospective study of 185 patients (100 women, 85 men; mean age, 66 years) who underwent lung cancer screening at a single health care system between July 2015 and August 2018. Using Lung-RADS, seven cancers were downgraded to category 2. The weighted cancer risk was 5% for new nodules, 1% for stable existing nodules, and 44% for growing existing nodules.

“Lung-RADS scores exhibited excellent sensitivity and specificity for cancer in existing nodules and excellent sensitivity in new nodules, though low specificity in new nodules,” wrote the authors, led by Mark M. Hammer, MD, a radiologist with Brigham and Women’s Hospital in Boston.

CT scans are increasingly used for lung cancer screening, so accuracy is essential in devising an appropriate treatment plan for patients. Nearly all centers in the United States use the American College of Radiology’s Lung-RADS for lung cancer screening. In Europe, many centers use the volumetric-based approach of NELSON.

Several studies have compared the performance of nodule risk assessment algorithms, but the findings are inconsistent. Lung-RADS was found to be inferior to the Vancouver risk calculator in predicting malignancy in the National Lung Screening Trial for total nodules. Dr. Hammer previously reported that subsolid nodules classified as Lung-RADS categories 2 and 3 have a higher risk of malignancy than reported. Meanwhile, a study that followed 13,195 men and 2,594 women at high risk of lung cancer found that lung cancer mortality was lower among participants who underwent volume CT screening than among those who underwent no screening.

The authors cited the retrospective design and the small sample size as study limitations. They added that pathological proof was not obtained from benign nodules, which may represent undiagnosed cancer.

The authors declared no conflict of interest.

A newly published study that compared the accuracy of two commonly used lung cancer screening algorithms found that the American College of Radiology Lung-RADs screening tool is more accurate in detecting cancerous nodules in patients with a history of lung cancer than NELSON, a Dutch clinical trial that measures nodule volume and growth rate instead of linear measurement of nodule size as done in Lung-RADs.

The study, published in the American Journal of Roentgenology on Nov. 10, 2021,was a retrospective study of 185 patients (100 women, 85 men; mean age, 66 years) who underwent lung cancer screening at a single health care system between July 2015 and August 2018. Using Lung-RADS, seven cancers were downgraded to category 2. The weighted cancer risk was 5% for new nodules, 1% for stable existing nodules, and 44% for growing existing nodules.

“Lung-RADS scores exhibited excellent sensitivity and specificity for cancer in existing nodules and excellent sensitivity in new nodules, though low specificity in new nodules,” wrote the authors, led by Mark M. Hammer, MD, a radiologist with Brigham and Women’s Hospital in Boston.

CT scans are increasingly used for lung cancer screening, so accuracy is essential in devising an appropriate treatment plan for patients. Nearly all centers in the United States use the American College of Radiology’s Lung-RADS for lung cancer screening. In Europe, many centers use the volumetric-based approach of NELSON.

Several studies have compared the performance of nodule risk assessment algorithms, but the findings are inconsistent. Lung-RADS was found to be inferior to the Vancouver risk calculator in predicting malignancy in the National Lung Screening Trial for total nodules. Dr. Hammer previously reported that subsolid nodules classified as Lung-RADS categories 2 and 3 have a higher risk of malignancy than reported. Meanwhile, a study that followed 13,195 men and 2,594 women at high risk of lung cancer found that lung cancer mortality was lower among participants who underwent volume CT screening than among those who underwent no screening.

The authors cited the retrospective design and the small sample size as study limitations. They added that pathological proof was not obtained from benign nodules, which may represent undiagnosed cancer.

The authors declared no conflict of interest.

A newly published study that compared the accuracy of two commonly used lung cancer screening algorithms found that the American College of Radiology Lung-RADs screening tool is more accurate in detecting cancerous nodules in patients with a history of lung cancer than NELSON, a Dutch clinical trial that measures nodule volume and growth rate instead of linear measurement of nodule size as done in Lung-RADs.

The study, published in the American Journal of Roentgenology on Nov. 10, 2021,was a retrospective study of 185 patients (100 women, 85 men; mean age, 66 years) who underwent lung cancer screening at a single health care system between July 2015 and August 2018. Using Lung-RADS, seven cancers were downgraded to category 2. The weighted cancer risk was 5% for new nodules, 1% for stable existing nodules, and 44% for growing existing nodules.

“Lung-RADS scores exhibited excellent sensitivity and specificity for cancer in existing nodules and excellent sensitivity in new nodules, though low specificity in new nodules,” wrote the authors, led by Mark M. Hammer, MD, a radiologist with Brigham and Women’s Hospital in Boston.

CT scans are increasingly used for lung cancer screening, so accuracy is essential in devising an appropriate treatment plan for patients. Nearly all centers in the United States use the American College of Radiology’s Lung-RADS for lung cancer screening. In Europe, many centers use the volumetric-based approach of NELSON.

Several studies have compared the performance of nodule risk assessment algorithms, but the findings are inconsistent. Lung-RADS was found to be inferior to the Vancouver risk calculator in predicting malignancy in the National Lung Screening Trial for total nodules. Dr. Hammer previously reported that subsolid nodules classified as Lung-RADS categories 2 and 3 have a higher risk of malignancy than reported. Meanwhile, a study that followed 13,195 men and 2,594 women at high risk of lung cancer found that lung cancer mortality was lower among participants who underwent volume CT screening than among those who underwent no screening.

The authors cited the retrospective design and the small sample size as study limitations. They added that pathological proof was not obtained from benign nodules, which may represent undiagnosed cancer.

The authors declared no conflict of interest.

SACRAMENTO – With access to abortion at stake across America, California is preparing to become the nation’s abortion provider.

Democratic Gov. Gavin Newsom and legislative leaders have asked a group of reproductive health experts to propose policies to bolster the state’s abortion infrastructure and ready it for more patients. Lawmakers plan to begin debating the ideas when they reconvene in January.

Abortion clinics are already girding themselves for a surge in demand.

Janet Jacobson, MD, medical director of Planned Parenthood of Orange and San Bernardino Counties, said three or four out-of-state patients visit her clinics each day – about double the number that sought treatment before a near-total ban on abortion took effect in Texas in September.

While the nine clinics can absorb that slow trickle, they expect up to 50 out-of-state patients a week if the U.S. Supreme Court’s conservative majority guts abortion rights nationally, Dr. Jacobson said. She bases her estimate on new data from the Guttmacher Institute, a research organization that supports abortion and reproductive health rights.

She is adding staff members and appointment capacity, hoping to accommodate everyone.

“We have to make sure we can still continue to care for all of our California patients,” Dr. Jacobson said. “We don’t want them getting squeezed out” of appointments.

The Texas law banned nearly all abortions after about 6 weeks of pregnancy and empowered private citizens to sue anyone who performs or “aids and abets” an abortion after that time. The Supreme Court heard arguments in that case on Nov. 1 and is expected to announce a ruling on its constitutionality in June. Nonetheless, Florida and Ohio have announced plans for copycat laws.

Next month the high court will hear another abortion case with even broader implications, Dobbs v. Jackson Women’s Health Organization, a lawsuit challenging the constitutionality of a 2018 Mississippi law that prohibited abortion after 15 weeks. If the court sides with Mississippi, its decision could overturn existing abortion rights set by the landmark Roe v. Wade case.

Should that happen, reproductive rights experts predict, 26 states will ban the procedure altogether, and states with stronger protections for abortion, like California, will draw even more patients. There could be up to a 3,000% increase in people who “may drive to California for abortion care” each year, according to the Guttmacher data.

In 2017, the most recent year for which data are available from Guttmacher, California – by far the nation’s most populous state – had more abortion providers than any other state, with 419 hospitals, clinics, or doctors’ offices performing the procedure. The next highest were New York, with 252, and Florida, with 85. Neighboring Arizona and Nevada each had 11. Of the 862,320 abortions performed in the United States that year, 132.680, about 15% were in California.

Planned Parenthood clinics in California say they already serve about 7,000 out-of-state patients a year and are expecting a surge of new ones, especially in travel hubs like the Los Angeles area.

In September, Planned Parenthood and groups such as Black Women for Wellness convened the California Future of Abortion Council with backing from influential Democratic leaders including Gov. Newsom, state Senate leader Toni Atkins, and Assembly Speaker Anthony Rendon.

Ms. Atkins, who was the director of a San Diego women’s health clinic in the 1980s, said she spent time with women from states where it was hard to get an abortion. She said California is committed to ensuring abortion access in the state and beyond.

The council is focused on increasing funding for abortion services, providing logistical and financial help for women who need to travel, increasing the number of health care providers who perform abortions, and strengthening legal protections for them.

Increasing capacity could mean licensing more practitioners to provide abortions or pumping more resources into telehealth so people can see a doctor online to prescribe pills for a medical abortion – a service California doctors currently can provide to patients only in California.

The most important thing the state should do is fix its shortage of providers, especially those who perform second-trimester abortions, which are more expensive and complicated than first-trimester abortions, said council member Daniel Grossman, MD, director of the Advancing New Standards in Reproductive Health program at the University of California, San Francisco.

It’s not feasible to place an abortion provider in every corner of the state, Dr. Grossman said. Instead, the council should focus on creating “hubs that can provide abortion care for large numbers of people” in easy-to-get-to locations.

California already struggles to provide abortions to all who seek them, especially low-income women covered by Medi-Cal, California’s Medicaid program. For example, 28 counties – home to 10% of Medi-Cal recipients of childbearing age – don’t have facilities that provide abortions to Medi-Cal patients.

A medical abortion, in which pills are used to terminate a pregnancy, costs California patients an average of $306 out-of-pocket, according to an analysis by the California Health Benefits Review Program, but isn’t available after 10 weeks. After that, the only option is a surgical abortion, which costs an average of $887 out-of-pocket in California.

One of the council’s recommendations will likely be to increase the rate Medi-Cal payments for abortions so more providers will perform them, said council member Fabiola Carrión, interim director for reproductive and sexual health at the National Health Law Program.

Medi-Cal pays $354.43 for a second-trimester abortion. A 2020 study in the journal Contraception found that states paid between $79 and $626 for a second-trimester abortion in 2017.

Increasing Medi-Cal rates won’t help patients traveling from outside California. Generally, private insurance doesn’t cover out-of-state abortions, so most women will be on the hook for the full cost, and those enrolled in other states’ Medicaid programs must pay out-of-pocket, too.

The council hopes to reduce costs for state residents and visitors, said Brandon Richards, director of communications for Planned Parenthood Affiliates of California. “It’s about making it easy for people to access abortion in California, whether they reside here or are coming in from out of state,” he said.

One way to target costs is by funding the practical support, like helping to pay for transportation, child care, hotels, or time off work, said council member Jessica Pinckney, executive director of Access Reproductive Justice, a fund that helps people pay for abortions.

Ms. Pinckney said she’s working with Los Angeles County to set up a public abortion fund to cover some of those costs for anyone seeking an abortion in the county. It would be modeled after similar pots maintained by the cities of New York; Austin, Tex.; and Portland, Ore., and could eventually be a template for the first statewide fund, Ms. Pinckney said.

Most Texans seeking abortions since that state’s law took effect are going to nearby states like Colorado, New Mexico, and Oklahoma, said Sierra Harris, deputy director of network strategies for the National Network of Abortion Funds. Women in those states, in turn, are having trouble getting care and are looking to California for appointments.

Practical support is important for out-of-state patients, said Alissa Perrucci, PhD, MPH, operations manager at the Women’s Options Center at Zuckerberg San Francisco General Hospital, one of five abortion clinics inside California hospitals.

Dr. Perrucci’s clinic is focusing on telemedicine, phone counseling, and other ways to save time so it can add appointments for out-of-state patients if necessary.

But more slots are useless if women can’t make it to California. The clinic has booked about 10 appointments for Texans since the state’s ban went into effect, but only half have shown up, mostly women with family connections in California.

“Most people just don’t have the money to get here,” she said. “If the burden of abortion was borne predominantly by the wealthy, yeah, they’d just fly here.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

SACRAMENTO – With access to abortion at stake across America, California is preparing to become the nation’s abortion provider.

Democratic Gov. Gavin Newsom and legislative leaders have asked a group of reproductive health experts to propose policies to bolster the state’s abortion infrastructure and ready it for more patients. Lawmakers plan to begin debating the ideas when they reconvene in January.

Abortion clinics are already girding themselves for a surge in demand.

Janet Jacobson, MD, medical director of Planned Parenthood of Orange and San Bernardino Counties, said three or four out-of-state patients visit her clinics each day – about double the number that sought treatment before a near-total ban on abortion took effect in Texas in September.

While the nine clinics can absorb that slow trickle, they expect up to 50 out-of-state patients a week if the U.S. Supreme Court’s conservative majority guts abortion rights nationally, Dr. Jacobson said. She bases her estimate on new data from the Guttmacher Institute, a research organization that supports abortion and reproductive health rights.

She is adding staff members and appointment capacity, hoping to accommodate everyone.

“We have to make sure we can still continue to care for all of our California patients,” Dr. Jacobson said. “We don’t want them getting squeezed out” of appointments.

The Texas law banned nearly all abortions after about 6 weeks of pregnancy and empowered private citizens to sue anyone who performs or “aids and abets” an abortion after that time. The Supreme Court heard arguments in that case on Nov. 1 and is expected to announce a ruling on its constitutionality in June. Nonetheless, Florida and Ohio have announced plans for copycat laws.

Next month the high court will hear another abortion case with even broader implications, Dobbs v. Jackson Women’s Health Organization, a lawsuit challenging the constitutionality of a 2018 Mississippi law that prohibited abortion after 15 weeks. If the court sides with Mississippi, its decision could overturn existing abortion rights set by the landmark Roe v. Wade case.

Should that happen, reproductive rights experts predict, 26 states will ban the procedure altogether, and states with stronger protections for abortion, like California, will draw even more patients. There could be up to a 3,000% increase in people who “may drive to California for abortion care” each year, according to the Guttmacher data.

In 2017, the most recent year for which data are available from Guttmacher, California – by far the nation’s most populous state – had more abortion providers than any other state, with 419 hospitals, clinics, or doctors’ offices performing the procedure. The next highest were New York, with 252, and Florida, with 85. Neighboring Arizona and Nevada each had 11. Of the 862,320 abortions performed in the United States that year, 132.680, about 15% were in California.

Planned Parenthood clinics in California say they already serve about 7,000 out-of-state patients a year and are expecting a surge of new ones, especially in travel hubs like the Los Angeles area.

In September, Planned Parenthood and groups such as Black Women for Wellness convened the California Future of Abortion Council with backing from influential Democratic leaders including Gov. Newsom, state Senate leader Toni Atkins, and Assembly Speaker Anthony Rendon.

Ms. Atkins, who was the director of a San Diego women’s health clinic in the 1980s, said she spent time with women from states where it was hard to get an abortion. She said California is committed to ensuring abortion access in the state and beyond.

The council is focused on increasing funding for abortion services, providing logistical and financial help for women who need to travel, increasing the number of health care providers who perform abortions, and strengthening legal protections for them.

Increasing capacity could mean licensing more practitioners to provide abortions or pumping more resources into telehealth so people can see a doctor online to prescribe pills for a medical abortion – a service California doctors currently can provide to patients only in California.

The most important thing the state should do is fix its shortage of providers, especially those who perform second-trimester abortions, which are more expensive and complicated than first-trimester abortions, said council member Daniel Grossman, MD, director of the Advancing New Standards in Reproductive Health program at the University of California, San Francisco.

It’s not feasible to place an abortion provider in every corner of the state, Dr. Grossman said. Instead, the council should focus on creating “hubs that can provide abortion care for large numbers of people” in easy-to-get-to locations.

California already struggles to provide abortions to all who seek them, especially low-income women covered by Medi-Cal, California’s Medicaid program. For example, 28 counties – home to 10% of Medi-Cal recipients of childbearing age – don’t have facilities that provide abortions to Medi-Cal patients.

A medical abortion, in which pills are used to terminate a pregnancy, costs California patients an average of $306 out-of-pocket, according to an analysis by the California Health Benefits Review Program, but isn’t available after 10 weeks. After that, the only option is a surgical abortion, which costs an average of $887 out-of-pocket in California.

One of the council’s recommendations will likely be to increase the rate Medi-Cal payments for abortions so more providers will perform them, said council member Fabiola Carrión, interim director for reproductive and sexual health at the National Health Law Program.

Medi-Cal pays $354.43 for a second-trimester abortion. A 2020 study in the journal Contraception found that states paid between $79 and $626 for a second-trimester abortion in 2017.

Increasing Medi-Cal rates won’t help patients traveling from outside California. Generally, private insurance doesn’t cover out-of-state abortions, so most women will be on the hook for the full cost, and those enrolled in other states’ Medicaid programs must pay out-of-pocket, too.

The council hopes to reduce costs for state residents and visitors, said Brandon Richards, director of communications for Planned Parenthood Affiliates of California. “It’s about making it easy for people to access abortion in California, whether they reside here or are coming in from out of state,” he said.

One way to target costs is by funding the practical support, like helping to pay for transportation, child care, hotels, or time off work, said council member Jessica Pinckney, executive director of Access Reproductive Justice, a fund that helps people pay for abortions.

Ms. Pinckney said she’s working with Los Angeles County to set up a public abortion fund to cover some of those costs for anyone seeking an abortion in the county. It would be modeled after similar pots maintained by the cities of New York; Austin, Tex.; and Portland, Ore., and could eventually be a template for the first statewide fund, Ms. Pinckney said.

Most Texans seeking abortions since that state’s law took effect are going to nearby states like Colorado, New Mexico, and Oklahoma, said Sierra Harris, deputy director of network strategies for the National Network of Abortion Funds. Women in those states, in turn, are having trouble getting care and are looking to California for appointments.

Practical support is important for out-of-state patients, said Alissa Perrucci, PhD, MPH, operations manager at the Women’s Options Center at Zuckerberg San Francisco General Hospital, one of five abortion clinics inside California hospitals.

Dr. Perrucci’s clinic is focusing on telemedicine, phone counseling, and other ways to save time so it can add appointments for out-of-state patients if necessary.

But more slots are useless if women can’t make it to California. The clinic has booked about 10 appointments for Texans since the state’s ban went into effect, but only half have shown up, mostly women with family connections in California.

“Most people just don’t have the money to get here,” she said. “If the burden of abortion was borne predominantly by the wealthy, yeah, they’d just fly here.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

SACRAMENTO – With access to abortion at stake across America, California is preparing to become the nation’s abortion provider.

Democratic Gov. Gavin Newsom and legislative leaders have asked a group of reproductive health experts to propose policies to bolster the state’s abortion infrastructure and ready it for more patients. Lawmakers plan to begin debating the ideas when they reconvene in January.

Abortion clinics are already girding themselves for a surge in demand.

Janet Jacobson, MD, medical director of Planned Parenthood of Orange and San Bernardino Counties, said three or four out-of-state patients visit her clinics each day – about double the number that sought treatment before a near-total ban on abortion took effect in Texas in September.

While the nine clinics can absorb that slow trickle, they expect up to 50 out-of-state patients a week if the U.S. Supreme Court’s conservative majority guts abortion rights nationally, Dr. Jacobson said. She bases her estimate on new data from the Guttmacher Institute, a research organization that supports abortion and reproductive health rights.

She is adding staff members and appointment capacity, hoping to accommodate everyone.

“We have to make sure we can still continue to care for all of our California patients,” Dr. Jacobson said. “We don’t want them getting squeezed out” of appointments.

The Texas law banned nearly all abortions after about 6 weeks of pregnancy and empowered private citizens to sue anyone who performs or “aids and abets” an abortion after that time. The Supreme Court heard arguments in that case on Nov. 1 and is expected to announce a ruling on its constitutionality in June. Nonetheless, Florida and Ohio have announced plans for copycat laws.

Next month the high court will hear another abortion case with even broader implications, Dobbs v. Jackson Women’s Health Organization, a lawsuit challenging the constitutionality of a 2018 Mississippi law that prohibited abortion after 15 weeks. If the court sides with Mississippi, its decision could overturn existing abortion rights set by the landmark Roe v. Wade case.

Should that happen, reproductive rights experts predict, 26 states will ban the procedure altogether, and states with stronger protections for abortion, like California, will draw even more patients. There could be up to a 3,000% increase in people who “may drive to California for abortion care” each year, according to the Guttmacher data.

In 2017, the most recent year for which data are available from Guttmacher, California – by far the nation’s most populous state – had more abortion providers than any other state, with 419 hospitals, clinics, or doctors’ offices performing the procedure. The next highest were New York, with 252, and Florida, with 85. Neighboring Arizona and Nevada each had 11. Of the 862,320 abortions performed in the United States that year, 132.680, about 15% were in California.

Planned Parenthood clinics in California say they already serve about 7,000 out-of-state patients a year and are expecting a surge of new ones, especially in travel hubs like the Los Angeles area.

In September, Planned Parenthood and groups such as Black Women for Wellness convened the California Future of Abortion Council with backing from influential Democratic leaders including Gov. Newsom, state Senate leader Toni Atkins, and Assembly Speaker Anthony Rendon.

Ms. Atkins, who was the director of a San Diego women’s health clinic in the 1980s, said she spent time with women from states where it was hard to get an abortion. She said California is committed to ensuring abortion access in the state and beyond.

The council is focused on increasing funding for abortion services, providing logistical and financial help for women who need to travel, increasing the number of health care providers who perform abortions, and strengthening legal protections for them.

Increasing capacity could mean licensing more practitioners to provide abortions or pumping more resources into telehealth so people can see a doctor online to prescribe pills for a medical abortion – a service California doctors currently can provide to patients only in California.

The most important thing the state should do is fix its shortage of providers, especially those who perform second-trimester abortions, which are more expensive and complicated than first-trimester abortions, said council member Daniel Grossman, MD, director of the Advancing New Standards in Reproductive Health program at the University of California, San Francisco.

It’s not feasible to place an abortion provider in every corner of the state, Dr. Grossman said. Instead, the council should focus on creating “hubs that can provide abortion care for large numbers of people” in easy-to-get-to locations.

California already struggles to provide abortions to all who seek them, especially low-income women covered by Medi-Cal, California’s Medicaid program. For example, 28 counties – home to 10% of Medi-Cal recipients of childbearing age – don’t have facilities that provide abortions to Medi-Cal patients.

A medical abortion, in which pills are used to terminate a pregnancy, costs California patients an average of $306 out-of-pocket, according to an analysis by the California Health Benefits Review Program, but isn’t available after 10 weeks. After that, the only option is a surgical abortion, which costs an average of $887 out-of-pocket in California.

One of the council’s recommendations will likely be to increase the rate Medi-Cal payments for abortions so more providers will perform them, said council member Fabiola Carrión, interim director for reproductive and sexual health at the National Health Law Program.

Medi-Cal pays $354.43 for a second-trimester abortion. A 2020 study in the journal Contraception found that states paid between $79 and $626 for a second-trimester abortion in 2017.

Increasing Medi-Cal rates won’t help patients traveling from outside California. Generally, private insurance doesn’t cover out-of-state abortions, so most women will be on the hook for the full cost, and those enrolled in other states’ Medicaid programs must pay out-of-pocket, too.

The council hopes to reduce costs for state residents and visitors, said Brandon Richards, director of communications for Planned Parenthood Affiliates of California. “It’s about making it easy for people to access abortion in California, whether they reside here or are coming in from out of state,” he said.

One way to target costs is by funding the practical support, like helping to pay for transportation, child care, hotels, or time off work, said council member Jessica Pinckney, executive director of Access Reproductive Justice, a fund that helps people pay for abortions.

Ms. Pinckney said she’s working with Los Angeles County to set up a public abortion fund to cover some of those costs for anyone seeking an abortion in the county. It would be modeled after similar pots maintained by the cities of New York; Austin, Tex.; and Portland, Ore., and could eventually be a template for the first statewide fund, Ms. Pinckney said.

Most Texans seeking abortions since that state’s law took effect are going to nearby states like Colorado, New Mexico, and Oklahoma, said Sierra Harris, deputy director of network strategies for the National Network of Abortion Funds. Women in those states, in turn, are having trouble getting care and are looking to California for appointments.

Practical support is important for out-of-state patients, said Alissa Perrucci, PhD, MPH, operations manager at the Women’s Options Center at Zuckerberg San Francisco General Hospital, one of five abortion clinics inside California hospitals.

Dr. Perrucci’s clinic is focusing on telemedicine, phone counseling, and other ways to save time so it can add appointments for out-of-state patients if necessary.

But more slots are useless if women can’t make it to California. The clinic has booked about 10 appointments for Texans since the state’s ban went into effect, but only half have shown up, mostly women with family connections in California.

“Most people just don’t have the money to get here,” she said. “If the burden of abortion was borne predominantly by the wealthy, yeah, they’d just fly here.”

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The Food and Drug Administration has given the green light to third, or booster doses of the Pfizer and Moderna vaccines for everyone over the age of 18, ahead of the busy winter holiday season.

“Authorizing the use of a single booster dose of either the Moderna or Pfizer-BioNTech COVID-19 vaccine for individuals 18 years of age and older helps to provide continued protection against COVID-19, including the serious consequences that can occur, such as hospitalization and death,” said acting FDA Commissioner Janet Woodcock, MD, in an FDA press statement.

The Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet on Nov. 19 to review the science supporting a more widespread need for booster doses, and is expected to vote on official recommendations for their use in the United States. The CDC director must then sign off on the panel’s recommendations.

“As soon as the FDA reviews those data and provides an authorization, we at CDC will act swiftly,” Rochelle P. Walensky, MD, MPH, said at a recent White House briefing.

Several states – including Louisiana, Maine, and Colorado – have already authorized boosters for all adults as cases rise in Europe and across the Western and Northeastern regions of the United States.

FDA officials said they hoped that widening eligibility for boosters would cut down on confusion for people and hopefully speed uptake of the shots.

“Streamlining the eligibility criteria and making booster doses available to all individuals 18 years of age and older will also help to eliminate confusion about who may receive a booster dose and ensure booster doses are available to all who may need one,” said Peter Marks, MD, PhD, who heads the FDA’s Center for Biologics Evaluation and Research.

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

The Food and Drug Administration has given the green light to third, or booster doses of the Pfizer and Moderna vaccines for everyone over the age of 18, ahead of the busy winter holiday season.

“Authorizing the use of a single booster dose of either the Moderna or Pfizer-BioNTech COVID-19 vaccine for individuals 18 years of age and older helps to provide continued protection against COVID-19, including the serious consequences that can occur, such as hospitalization and death,” said acting FDA Commissioner Janet Woodcock, MD, in an FDA press statement.

The Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet on Nov. 19 to review the science supporting a more widespread need for booster doses, and is expected to vote on official recommendations for their use in the United States. The CDC director must then sign off on the panel’s recommendations.

“As soon as the FDA reviews those data and provides an authorization, we at CDC will act swiftly,” Rochelle P. Walensky, MD, MPH, said at a recent White House briefing.

Several states – including Louisiana, Maine, and Colorado – have already authorized boosters for all adults as cases rise in Europe and across the Western and Northeastern regions of the United States.

FDA officials said they hoped that widening eligibility for boosters would cut down on confusion for people and hopefully speed uptake of the shots.

“Streamlining the eligibility criteria and making booster doses available to all individuals 18 years of age and older will also help to eliminate confusion about who may receive a booster dose and ensure booster doses are available to all who may need one,” said Peter Marks, MD, PhD, who heads the FDA’s Center for Biologics Evaluation and Research.

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

The Food and Drug Administration has given the green light to third, or booster doses of the Pfizer and Moderna vaccines for everyone over the age of 18, ahead of the busy winter holiday season.

“Authorizing the use of a single booster dose of either the Moderna or Pfizer-BioNTech COVID-19 vaccine for individuals 18 years of age and older helps to provide continued protection against COVID-19, including the serious consequences that can occur, such as hospitalization and death,” said acting FDA Commissioner Janet Woodcock, MD, in an FDA press statement.

The Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet on Nov. 19 to review the science supporting a more widespread need for booster doses, and is expected to vote on official recommendations for their use in the United States. The CDC director must then sign off on the panel’s recommendations.

“As soon as the FDA reviews those data and provides an authorization, we at CDC will act swiftly,” Rochelle P. Walensky, MD, MPH, said at a recent White House briefing.

Several states – including Louisiana, Maine, and Colorado – have already authorized boosters for all adults as cases rise in Europe and across the Western and Northeastern regions of the United States.

FDA officials said they hoped that widening eligibility for boosters would cut down on confusion for people and hopefully speed uptake of the shots.

“Streamlining the eligibility criteria and making booster doses available to all individuals 18 years of age and older will also help to eliminate confusion about who may receive a booster dose and ensure booster doses are available to all who may need one,” said Peter Marks, MD, PhD, who heads the FDA’s Center for Biologics Evaluation and Research.

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

When people wear face masks to reduce the spread of the coronavirus, the number of new COVID-19 infections drops by 53%, according to a new study published Nov. 18 in the British Medical Journal.

Social distancing and handwashing were also effective at lowering the number of cases, but wearing masks was the most effective tool against the coronavirus.

“Personal and social measures, including handwashing, mask wearing, and physical distancing are effective at reducing the incidence of COVID-19,” the study authors wrote.

The research team, which included public health and infectious disease specialists in Australia, China, and the U.K., evaluated 72 studies of COVID-19 precautions during the pandemic. They later looked at eight studies that focused on handwashing, mask wearing, and physical distancing.

Among six studies that looked at mask wearing, the researchers found a 53% reduction in COVID-19 cases. In the broader analysis with additional studies, wearing a mask reduced coronavirus transmission, cases, and deaths.

In one study across 200 countries, mandatory mask wearing resulted in nearly 46% fewer negative outcomes from COVID-19. In another study in the U.S., coronavirus transmission was reduced 29% in states where masks were mandatory.

But the research team couldn’t analyze the impact of the type of face mask used, the frequency of mask wearing, or the overall compliance with wearing face masks.

Among five studies that looked at physical distancing, the researchers found a 25% reduction in the rate of COVID-19. A study in the U.S. showed a 12% decrease in coronavirus transmission, while another study in Iran reported a reduction in COVID-19 mortality.

Handwashing interventions also suggested a substantial reduction of COVID-19 cases up to 53%, the researchers wrote. But in adjusted models, the results weren’t statistically significant due to the small number of studies included.

Other studies found significant decreases related to other public health measures, such as quarantines, broad lockdowns, border closures, school closures, business closures, and travel restrictions. Still, the research team couldn’t analyze the overall effectiveness of these measures due to the different ways the studies were conducted.

The study lines up with other research conducted so far during the pandemic, the research team wrote, which indicates that wearing masks and physical distancing can reduce transmission, cases, and deaths.

That said, more studies are needed, particularly now that vaccinations are available and contagious coronavirus variants have become prevalent.

“Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage has been achieved,” they wrote.

“It is likely that further control of the COVID-19 pandemic depends not only on high vaccination coverage and its effectiveness but also on ongoing adherence to effective and sustainable public health measures,” they concluded.

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

When people wear face masks to reduce the spread of the coronavirus, the number of new COVID-19 infections drops by 53%, according to a new study published Nov. 18 in the British Medical Journal.

Social distancing and handwashing were also effective at lowering the number of cases, but wearing masks was the most effective tool against the coronavirus.

“Personal and social measures, including handwashing, mask wearing, and physical distancing are effective at reducing the incidence of COVID-19,” the study authors wrote.

The research team, which included public health and infectious disease specialists in Australia, China, and the U.K., evaluated 72 studies of COVID-19 precautions during the pandemic. They later looked at eight studies that focused on handwashing, mask wearing, and physical distancing.

Among six studies that looked at mask wearing, the researchers found a 53% reduction in COVID-19 cases. In the broader analysis with additional studies, wearing a mask reduced coronavirus transmission, cases, and deaths.

In one study across 200 countries, mandatory mask wearing resulted in nearly 46% fewer negative outcomes from COVID-19. In another study in the U.S., coronavirus transmission was reduced 29% in states where masks were mandatory.

But the research team couldn’t analyze the impact of the type of face mask used, the frequency of mask wearing, or the overall compliance with wearing face masks.

Among five studies that looked at physical distancing, the researchers found a 25% reduction in the rate of COVID-19. A study in the U.S. showed a 12% decrease in coronavirus transmission, while another study in Iran reported a reduction in COVID-19 mortality.

Handwashing interventions also suggested a substantial reduction of COVID-19 cases up to 53%, the researchers wrote. But in adjusted models, the results weren’t statistically significant due to the small number of studies included.

Other studies found significant decreases related to other public health measures, such as quarantines, broad lockdowns, border closures, school closures, business closures, and travel restrictions. Still, the research team couldn’t analyze the overall effectiveness of these measures due to the different ways the studies were conducted.

The study lines up with other research conducted so far during the pandemic, the research team wrote, which indicates that wearing masks and physical distancing can reduce transmission, cases, and deaths.

That said, more studies are needed, particularly now that vaccinations are available and contagious coronavirus variants have become prevalent.

“Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage has been achieved,” they wrote.

“It is likely that further control of the COVID-19 pandemic depends not only on high vaccination coverage and its effectiveness but also on ongoing adherence to effective and sustainable public health measures,” they concluded.

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

When people wear face masks to reduce the spread of the coronavirus, the number of new COVID-19 infections drops by 53%, according to a new study published Nov. 18 in the British Medical Journal.

Social distancing and handwashing were also effective at lowering the number of cases, but wearing masks was the most effective tool against the coronavirus.

“Personal and social measures, including handwashing, mask wearing, and physical distancing are effective at reducing the incidence of COVID-19,” the study authors wrote.

The research team, which included public health and infectious disease specialists in Australia, China, and the U.K., evaluated 72 studies of COVID-19 precautions during the pandemic. They later looked at eight studies that focused on handwashing, mask wearing, and physical distancing.

Among six studies that looked at mask wearing, the researchers found a 53% reduction in COVID-19 cases. In the broader analysis with additional studies, wearing a mask reduced coronavirus transmission, cases, and deaths.

In one study across 200 countries, mandatory mask wearing resulted in nearly 46% fewer negative outcomes from COVID-19. In another study in the U.S., coronavirus transmission was reduced 29% in states where masks were mandatory.

But the research team couldn’t analyze the impact of the type of face mask used, the frequency of mask wearing, or the overall compliance with wearing face masks.

Among five studies that looked at physical distancing, the researchers found a 25% reduction in the rate of COVID-19. A study in the U.S. showed a 12% decrease in coronavirus transmission, while another study in Iran reported a reduction in COVID-19 mortality.

Handwashing interventions also suggested a substantial reduction of COVID-19 cases up to 53%, the researchers wrote. But in adjusted models, the results weren’t statistically significant due to the small number of studies included.

Other studies found significant decreases related to other public health measures, such as quarantines, broad lockdowns, border closures, school closures, business closures, and travel restrictions. Still, the research team couldn’t analyze the overall effectiveness of these measures due to the different ways the studies were conducted.

The study lines up with other research conducted so far during the pandemic, the research team wrote, which indicates that wearing masks and physical distancing can reduce transmission, cases, and deaths.

That said, more studies are needed, particularly now that vaccinations are available and contagious coronavirus variants have become prevalent.

“Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage has been achieved,” they wrote.

“It is likely that further control of the COVID-19 pandemic depends not only on high vaccination coverage and its effectiveness but also on ongoing adherence to effective and sustainable public health measures,” they concluded.

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

Chronic kidney disease (CKD) had no impact on the efficacy or safety of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim) for patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved trial, showing once again that agents in this class are appropriate for patients with heart failure even when their kidney function is severely compromised.

More than half of the nearly 6,000 patients with heart failure and HFpEF enrolled in EMPEROR-Preserved had CKD (although renal function was not an enrollment criterion), including 10% with an estimated glomerular filtration rate (eGFR) that fell in the range of 20-29 mL/min/1.73 m2, which categorized them as having stage 4 CKD.

The results showed, in a prespecified analysis, that treatment with empagliflozin led to a consistent, significant relative risk reduction compared with placebo in the primary endpoint of cardiovascular death or hospitalization for heart failure “across the full spectrum of kidney function, down to an eGFR of 20 mL/min/1.73m2,” said Faiez Zannad, MD, PhD, who presented the findings at the annual meeting of the American Society of Nephrology.

Among the 46.5% of enrolled patients without CKD, empagliflozin produced a significant 20% drop in the primary outcome relative to those who received placebo. Among the 53.5% of patients with CKD at time of randomization (defined as an eGFR <60 mL/min/1/73 m2 or a urinary albumin to creatinine ratio >300 mg/g), treatment with empagliflozin was associated with a significant 25% cut in the primary endpoint compared with placebo.

Empagliflozin was also “well tolerated” by patients with HFpEF, whether or not they also had CKD, “including patients with severely impaired kidney function,” said Dr. Zannad, a professor of cardiology therapeutics at the University of Lorraine in Nancy, France, at the virtual meeting.
 

An end to ‘renalism’

“This is a nail in the coffin for the concept of ‘renalism,’” the erroneous notion held by many clinicians and researchers that various treatments are not as effective and potentially more likely to cause adverse effects in patients with CKD compared with those with better renal function, commented Janani Rangaswami, MD, a nephrologist who is a professor and director of the cardiorenal program at George Washington University, Washington, D.C.   

In addition to EMPEROR-Preserved, other large trials of agents from the SGLT2 inhibitor class bucked the premise of renalism and took the “groundbreaking step” of enrolling patients with moderate-severe CKD, noted Dr. Rangaswami in an interview. In particular, two trials took this approach when enrolling patients with heart failure with reduced ejection fraction (HFrEF), EMPEROR-Reduced (which also tested empagliflozin and matched the design of EMPEROR-Preserved) and DAPA-HF (which tested the SGLT2 inhibitor dapagliflozin [Farxiga, AstraZeneca]).

“It was a huge, bold step, especially in EMPEROR-Preserved and in EMPEROR-Reduced, which both enrolled patients with eGFRs as low as 20 mL/min/1.73m2,” Dr. Rangaswami said. DAPA-HF included patients with eGFRs as low as 30 mL/min/1.73m2.

EMPEROR-Reduced and DAPA-HF – published earlier this year – both had similar findings as EMPEROR-Preserved as reported by Dr. Zannad: consistent benefit from empagliflozin or dapagliflozin regardless of eGFR level and no signal of increased adverse events from treatment.

In fact, all three analyses show that patients with worse renal function had the highest risk for cardiovascular death and hospitalization for heart failure; hence, the beneficial impact from SGLT2 inhibitors is greatest in these patients.

These observations “make it easier to focus on the group with moderate-to-severe CKD,” both in the routine care setting as well as in future trials, said Dr. Rangaswami.

“This is a welcome trend that paves the way to test more treatments in patients with stage 4 and even stage 5 CKD, patients ... excluded from trials in the past,” she said.

In addition, the consistent benefit from SGLT2 inhibitors in these three heart failure trials regardless of CKD “means there is simply no room for renalism. There is no room for clinicians to say that because a patient’s eGFR is 30 mL/min/1.73m2 they are worried about starting an SGLT2 inhibitor,” she stressed.
 

More CKD-independent effects of empagliflozin

Results of other new analyses from EMPEROR-Preserved, also reported by Dr. Zannad, included the finding that empagliflozin was associated with a similar slowing of loss of renal function over time compared with placebo, regardless of CKD status.

In patients with CKD, empagliflozin slowed eGFR loss by 1.4 mL/min/1.73 m2/year, and in those without CKD, by 1.3 mL/min/1.73 m2/year, relative to placebo.

“Even in patients without CKD, there was a relevant eGFR decline in the placebo group that was attenuated by empagliflozin,” Dr. Zannad said.

At the end of the study, when empagliflozin was stopped, patients with or without CKD had their eGFR bounce back by an identical 2.4 mL/min/1.73 m2 relative to placebo.

Empagliflozin slowed progression to macroalbuminuria and significantly reduced the incidence of acute kidney injury by a similar amount regardless of CKD status compared with placebo.

EMPEROR-Preserved enrolled patients with function-limiting HFpEF, a left ventricular ejection fraction >40%, and a minimum level of a reliable serum marker of heart failure, N-terminal pro-B-type natriuretic peptide (NT-proBNP). Compared with placebo, empagliflozin reduced the trial’s primary outcome by an absolute 3.3 percentage points and by a significant relative risk reduction of 21% after a median 26 months of follow-up, according to a report published in October 2021.

EMPEROR-Preserved is the first prospective, randomized trial to unequivocally show the efficacy and safety of a drug for improving outcomes in patients with HFpEF.

EMPEROR-Preserved was sponsored by Boehringer-Ingelheim and Lilly, which market empagliflozin (Jardiance). Dr. Zannad has reported financial relationships with Boehringer Ingelheim as well as other companies. Dr. Rangaswami has reported being a consultant for Boehringer Ingelheim, Lilly, and AstraZeneca.

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

Chronic kidney disease (CKD) had no impact on the efficacy or safety of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim) for patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved trial, showing once again that agents in this class are appropriate for patients with heart failure even when their kidney function is severely compromised.

More than half of the nearly 6,000 patients with heart failure and HFpEF enrolled in EMPEROR-Preserved had CKD (although renal function was not an enrollment criterion), including 10% with an estimated glomerular filtration rate (eGFR) that fell in the range of 20-29 mL/min/1.73 m2, which categorized them as having stage 4 CKD.

The results showed, in a prespecified analysis, that treatment with empagliflozin led to a consistent, significant relative risk reduction compared with placebo in the primary endpoint of cardiovascular death or hospitalization for heart failure “across the full spectrum of kidney function, down to an eGFR of 20 mL/min/1.73m2,” said Faiez Zannad, MD, PhD, who presented the findings at the annual meeting of the American Society of Nephrology.

Among the 46.5% of enrolled patients without CKD, empagliflozin produced a significant 20% drop in the primary outcome relative to those who received placebo. Among the 53.5% of patients with CKD at time of randomization (defined as an eGFR <60 mL/min/1/73 m2 or a urinary albumin to creatinine ratio >300 mg/g), treatment with empagliflozin was associated with a significant 25% cut in the primary endpoint compared with placebo.

Empagliflozin was also “well tolerated” by patients with HFpEF, whether or not they also had CKD, “including patients with severely impaired kidney function,” said Dr. Zannad, a professor of cardiology therapeutics at the University of Lorraine in Nancy, France, at the virtual meeting.
 

An end to ‘renalism’

“This is a nail in the coffin for the concept of ‘renalism,’” the erroneous notion held by many clinicians and researchers that various treatments are not as effective and potentially more likely to cause adverse effects in patients with CKD compared with those with better renal function, commented Janani Rangaswami, MD, a nephrologist who is a professor and director of the cardiorenal program at George Washington University, Washington, D.C.   

In addition to EMPEROR-Preserved, other large trials of agents from the SGLT2 inhibitor class bucked the premise of renalism and took the “groundbreaking step” of enrolling patients with moderate-severe CKD, noted Dr. Rangaswami in an interview. In particular, two trials took this approach when enrolling patients with heart failure with reduced ejection fraction (HFrEF), EMPEROR-Reduced (which also tested empagliflozin and matched the design of EMPEROR-Preserved) and DAPA-HF (which tested the SGLT2 inhibitor dapagliflozin [Farxiga, AstraZeneca]).

“It was a huge, bold step, especially in EMPEROR-Preserved and in EMPEROR-Reduced, which both enrolled patients with eGFRs as low as 20 mL/min/1.73m2,” Dr. Rangaswami said. DAPA-HF included patients with eGFRs as low as 30 mL/min/1.73m2.

EMPEROR-Reduced and DAPA-HF – published earlier this year – both had similar findings as EMPEROR-Preserved as reported by Dr. Zannad: consistent benefit from empagliflozin or dapagliflozin regardless of eGFR level and no signal of increased adverse events from treatment.

In fact, all three analyses show that patients with worse renal function had the highest risk for cardiovascular death and hospitalization for heart failure; hence, the beneficial impact from SGLT2 inhibitors is greatest in these patients.

These observations “make it easier to focus on the group with moderate-to-severe CKD,” both in the routine care setting as well as in future trials, said Dr. Rangaswami.

“This is a welcome trend that paves the way to test more treatments in patients with stage 4 and even stage 5 CKD, patients ... excluded from trials in the past,” she said.

In addition, the consistent benefit from SGLT2 inhibitors in these three heart failure trials regardless of CKD “means there is simply no room for renalism. There is no room for clinicians to say that because a patient’s eGFR is 30 mL/min/1.73m2 they are worried about starting an SGLT2 inhibitor,” she stressed.
 

More CKD-independent effects of empagliflozin

Results of other new analyses from EMPEROR-Preserved, also reported by Dr. Zannad, included the finding that empagliflozin was associated with a similar slowing of loss of renal function over time compared with placebo, regardless of CKD status.

In patients with CKD, empagliflozin slowed eGFR loss by 1.4 mL/min/1.73 m2/year, and in those without CKD, by 1.3 mL/min/1.73 m2/year, relative to placebo.

“Even in patients without CKD, there was a relevant eGFR decline in the placebo group that was attenuated by empagliflozin,” Dr. Zannad said.

At the end of the study, when empagliflozin was stopped, patients with or without CKD had their eGFR bounce back by an identical 2.4 mL/min/1.73 m2 relative to placebo.

Empagliflozin slowed progression to macroalbuminuria and significantly reduced the incidence of acute kidney injury by a similar amount regardless of CKD status compared with placebo.

EMPEROR-Preserved enrolled patients with function-limiting HFpEF, a left ventricular ejection fraction >40%, and a minimum level of a reliable serum marker of heart failure, N-terminal pro-B-type natriuretic peptide (NT-proBNP). Compared with placebo, empagliflozin reduced the trial’s primary outcome by an absolute 3.3 percentage points and by a significant relative risk reduction of 21% after a median 26 months of follow-up, according to a report published in October 2021.

EMPEROR-Preserved is the first prospective, randomized trial to unequivocally show the efficacy and safety of a drug for improving outcomes in patients with HFpEF.

EMPEROR-Preserved was sponsored by Boehringer-Ingelheim and Lilly, which market empagliflozin (Jardiance). Dr. Zannad has reported financial relationships with Boehringer Ingelheim as well as other companies. Dr. Rangaswami has reported being a consultant for Boehringer Ingelheim, Lilly, and AstraZeneca.

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

Chronic kidney disease (CKD) had no impact on the efficacy or safety of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim) for patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved trial, showing once again that agents in this class are appropriate for patients with heart failure even when their kidney function is severely compromised.

More than half of the nearly 6,000 patients with heart failure and HFpEF enrolled in EMPEROR-Preserved had CKD (although renal function was not an enrollment criterion), including 10% with an estimated glomerular filtration rate (eGFR) that fell in the range of 20-29 mL/min/1.73 m2, which categorized them as having stage 4 CKD.

The results showed, in a prespecified analysis, that treatment with empagliflozin led to a consistent, significant relative risk reduction compared with placebo in the primary endpoint of cardiovascular death or hospitalization for heart failure “across the full spectrum of kidney function, down to an eGFR of 20 mL/min/1.73m2,” said Faiez Zannad, MD, PhD, who presented the findings at the annual meeting of the American Society of Nephrology.

Among the 46.5% of enrolled patients without CKD, empagliflozin produced a significant 20% drop in the primary outcome relative to those who received placebo. Among the 53.5% of patients with CKD at time of randomization (defined as an eGFR <60 mL/min/1/73 m2 or a urinary albumin to creatinine ratio >300 mg/g), treatment with empagliflozin was associated with a significant 25% cut in the primary endpoint compared with placebo.

Empagliflozin was also “well tolerated” by patients with HFpEF, whether or not they also had CKD, “including patients with severely impaired kidney function,” said Dr. Zannad, a professor of cardiology therapeutics at the University of Lorraine in Nancy, France, at the virtual meeting.
 

An end to ‘renalism’

“This is a nail in the coffin for the concept of ‘renalism,’” the erroneous notion held by many clinicians and researchers that various treatments are not as effective and potentially more likely to cause adverse effects in patients with CKD compared with those with better renal function, commented Janani Rangaswami, MD, a nephrologist who is a professor and director of the cardiorenal program at George Washington University, Washington, D.C.   

In addition to EMPEROR-Preserved, other large trials of agents from the SGLT2 inhibitor class bucked the premise of renalism and took the “groundbreaking step” of enrolling patients with moderate-severe CKD, noted Dr. Rangaswami in an interview. In particular, two trials took this approach when enrolling patients with heart failure with reduced ejection fraction (HFrEF), EMPEROR-Reduced (which also tested empagliflozin and matched the design of EMPEROR-Preserved) and DAPA-HF (which tested the SGLT2 inhibitor dapagliflozin [Farxiga, AstraZeneca]).

“It was a huge, bold step, especially in EMPEROR-Preserved and in EMPEROR-Reduced, which both enrolled patients with eGFRs as low as 20 mL/min/1.73m2,” Dr. Rangaswami said. DAPA-HF included patients with eGFRs as low as 30 mL/min/1.73m2.

EMPEROR-Reduced and DAPA-HF – published earlier this year – both had similar findings as EMPEROR-Preserved as reported by Dr. Zannad: consistent benefit from empagliflozin or dapagliflozin regardless of eGFR level and no signal of increased adverse events from treatment.

In fact, all three analyses show that patients with worse renal function had the highest risk for cardiovascular death and hospitalization for heart failure; hence, the beneficial impact from SGLT2 inhibitors is greatest in these patients.

These observations “make it easier to focus on the group with moderate-to-severe CKD,” both in the routine care setting as well as in future trials, said Dr. Rangaswami.

“This is a welcome trend that paves the way to test more treatments in patients with stage 4 and even stage 5 CKD, patients ... excluded from trials in the past,” she said.

In addition, the consistent benefit from SGLT2 inhibitors in these three heart failure trials regardless of CKD “means there is simply no room for renalism. There is no room for clinicians to say that because a patient’s eGFR is 30 mL/min/1.73m2 they are worried about starting an SGLT2 inhibitor,” she stressed.
 

More CKD-independent effects of empagliflozin

Results of other new analyses from EMPEROR-Preserved, also reported by Dr. Zannad, included the finding that empagliflozin was associated with a similar slowing of loss of renal function over time compared with placebo, regardless of CKD status.

In patients with CKD, empagliflozin slowed eGFR loss by 1.4 mL/min/1.73 m2/year, and in those without CKD, by 1.3 mL/min/1.73 m2/year, relative to placebo.

“Even in patients without CKD, there was a relevant eGFR decline in the placebo group that was attenuated by empagliflozin,” Dr. Zannad said.

At the end of the study, when empagliflozin was stopped, patients with or without CKD had their eGFR bounce back by an identical 2.4 mL/min/1.73 m2 relative to placebo.

Empagliflozin slowed progression to macroalbuminuria and significantly reduced the incidence of acute kidney injury by a similar amount regardless of CKD status compared with placebo.

EMPEROR-Preserved enrolled patients with function-limiting HFpEF, a left ventricular ejection fraction >40%, and a minimum level of a reliable serum marker of heart failure, N-terminal pro-B-type natriuretic peptide (NT-proBNP). Compared with placebo, empagliflozin reduced the trial’s primary outcome by an absolute 3.3 percentage points and by a significant relative risk reduction of 21% after a median 26 months of follow-up, according to a report published in October 2021.

EMPEROR-Preserved is the first prospective, randomized trial to unequivocally show the efficacy and safety of a drug for improving outcomes in patients with HFpEF.

EMPEROR-Preserved was sponsored by Boehringer-Ingelheim and Lilly, which market empagliflozin (Jardiance). Dr. Zannad has reported financial relationships with Boehringer Ingelheim as well as other companies. Dr. Rangaswami has reported being a consultant for Boehringer Ingelheim, Lilly, and AstraZeneca.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

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

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

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

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

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