Similarly, Lin et al report the results of an international study of adults from 99 countries, which utilized longitudinal mobile based surveys to examine risk factors associated with SARS-CoV-2 infection. The mobile surveys captured baseline characteristics and behaviors of participants, and data was reported out for the study period of March to October 2020 (before vaccines were available). Adjusting for demographics, education level, a proxy for occupational risk, as well as medical comorbidities, authors found that greater number of non-household contacts, attending events with 10 or more individuals and restaurant visits predicted higher risk of SARS-CoV-2. Alternatively, older age was associated with lower risk, likely because of the protective behaviors undertaken by many in the older age group.

Lastly, the RECoVERED Study (Wynberg, at al), based in Netherlands, followed recently diagnosed laboratory confirmed SARS-CoV-2 patients for a year, initially with three in person visits (where disease severity was determined based on vital signs and level of care needed) within the first month of illness and then monthly online surveys. Authors utilized a survey examining severity of 18 symptoms based on the World Health Organization Case Report Form. Authors found 86.7% of those with initial severe disease [95% confidence interval {CI} = 76.5–92.7%]), 63.8%  of those moderate disease 63.8% [95% CI = 54.8–71.5%], and 30.7% of those with mild disease [95% CI = 21.1–40.9%] had at least one persistent symptom at 12 weeks.  Fatigue was the most common symptom reported at 12 weeks overall, but among those with moderate and severe disease, dyspnea and myalgia also persisted frequently. After one years of follow up, about one-fifth still had one persistent symptom. Over half of those with initial severe disease reported symptom persistence (52.5% [95% CI = 38.0–65.1%]). In a multivariable Cox proportional hazard model, female sex and higher BMI were associated with slower recovery. One limitation of the study was that was no control group recruited.

Similarly, Lin et al report the results of an international study of adults from 99 countries, which utilized longitudinal mobile based surveys to examine risk factors associated with SARS-CoV-2 infection. The mobile surveys captured baseline characteristics and behaviors of participants, and data was reported out for the study period of March to October 2020 (before vaccines were available). Adjusting for demographics, education level, a proxy for occupational risk, as well as medical comorbidities, authors found that greater number of non-household contacts, attending events with 10 or more individuals and restaurant visits predicted higher risk of SARS-CoV-2. Alternatively, older age was associated with lower risk, likely because of the protective behaviors undertaken by many in the older age group.

Lastly, the RECoVERED Study (Wynberg, at al), based in Netherlands, followed recently diagnosed laboratory confirmed SARS-CoV-2 patients for a year, initially with three in person visits (where disease severity was determined based on vital signs and level of care needed) within the first month of illness and then monthly online surveys. Authors utilized a survey examining severity of 18 symptoms based on the World Health Organization Case Report Form. Authors found 86.7% of those with initial severe disease [95% confidence interval {CI} = 76.5–92.7%]), 63.8%  of those moderate disease 63.8% [95% CI = 54.8–71.5%], and 30.7% of those with mild disease [95% CI = 21.1–40.9%] had at least one persistent symptom at 12 weeks.  Fatigue was the most common symptom reported at 12 weeks overall, but among those with moderate and severe disease, dyspnea and myalgia also persisted frequently. After one years of follow up, about one-fifth still had one persistent symptom. Over half of those with initial severe disease reported symptom persistence (52.5% [95% CI = 38.0–65.1%]). In a multivariable Cox proportional hazard model, female sex and higher BMI were associated with slower recovery. One limitation of the study was that was no control group recruited.

Similarly, Lin et al report the results of an international study of adults from 99 countries, which utilized longitudinal mobile based surveys to examine risk factors associated with SARS-CoV-2 infection. The mobile surveys captured baseline characteristics and behaviors of participants, and data was reported out for the study period of March to October 2020 (before vaccines were available). Adjusting for demographics, education level, a proxy for occupational risk, as well as medical comorbidities, authors found that greater number of non-household contacts, attending events with 10 or more individuals and restaurant visits predicted higher risk of SARS-CoV-2. Alternatively, older age was associated with lower risk, likely because of the protective behaviors undertaken by many in the older age group.

Lastly, the RECoVERED Study (Wynberg, at al), based in Netherlands, followed recently diagnosed laboratory confirmed SARS-CoV-2 patients for a year, initially with three in person visits (where disease severity was determined based on vital signs and level of care needed) within the first month of illness and then monthly online surveys. Authors utilized a survey examining severity of 18 symptoms based on the World Health Organization Case Report Form. Authors found 86.7% of those with initial severe disease [95% confidence interval {CI} = 76.5–92.7%]), 63.8%  of those moderate disease 63.8% [95% CI = 54.8–71.5%], and 30.7% of those with mild disease [95% CI = 21.1–40.9%] had at least one persistent symptom at 12 weeks.  Fatigue was the most common symptom reported at 12 weeks overall, but among those with moderate and severe disease, dyspnea and myalgia also persisted frequently. After one years of follow up, about one-fifth still had one persistent symptom. Over half of those with initial severe disease reported symptom persistence (52.5% [95% CI = 38.0–65.1%]). In a multivariable Cox proportional hazard model, female sex and higher BMI were associated with slower recovery. One limitation of the study was that was no control group recruited.

Inside the emergency department at Sparrow Hospital in Lansing, Mich., staff members are struggling to care for patients showing up much sicker than they’ve ever seen.

Tiffani Dusang, the ER’s nursing director, practically vibrates with pent-up anxiety, looking at patients lying on a long line of stretchers pushed up against the beige walls of the hospital hallways. “It’s hard to watch,” she said in a warm Texas twang.

But there’s nothing she can do. The ER’s 72 rooms are already filled.

“I always feel very, very bad when I walk down the hallway and see that people are in pain, or needing to sleep, or needing quiet. But they have to be in the hallway with, as you can see, 10 or 15 people walking by every minute,” Ms. Dusang said.

The scene is a stark contrast to where this emergency department — and thousands of others — were at the start of the pandemic. Except for initial hot spots like New York City, in spring 2020 many ERs across the country were often eerily empty. Terrified of contracting COVID-19, people who were sick with other things did their best to stay away from hospitals. Visits to emergency rooms dropped to half their typical levels, according to the Epic Health Research Network, and didn’t fully rebound until this summer.

But now, they’re too full. Even in parts of the country where covid isn’t overwhelming the health system, patients are showing up to the ER sicker than before the pandemic, their diseases more advanced and in need of more complicated care.

Months of treatment delays have exacerbated chronic conditions and worsened symptoms. Doctors and nurses say the severity of illness ranges widely and includes abdominal pain, respiratory problems, blood clots, heart conditions and suicide attempts, among other conditions.

But they can hardly be accommodated. Emergency departments, ideally, are meant to be brief ports in a storm, with patients staying just long enough to be sent home with instructions to follow up with primary care physicians, or sufficiently stabilized to be transferred “upstairs” to inpatient or intensive care units.

Except now those long-term care floors are full too, with a mix of covid and non-covid patients. People coming to the ER get warehoused for hours, even days, forcing ER staffers to perform long-term care roles they weren’t trained to do.

At Sparrow, space is a valuable commodity in the ER: A separate section of the hospital was turned into an overflow unit. Stretchers stack up in halls. A row of brown reclining chairs lines a wall, intended for patients who aren’t sick enough for a stretcher but are too sick to stay in the main waiting room.

Forget privacy, Alejos Perrientoz learned when he arrived. He came to the ER because his arm had been tingling and painful for over a week. He couldn’t hold a cup of coffee. A nurse gave him a full physical exam in a brown recliner, which made him self-conscious about having his shirt lifted in front of strangers. “I felt a little uncomfortable,” he whispered. “But I have no choice, you know? I’m in the hallway. There’s no rooms.

“We could have done the physical in the parking lot,” he added, managing a laugh.

Even patients who arrive by ambulance are not guaranteed a room: One nurse runs triage, screening those who absolutely need a bed, and those who can be put in the waiting area.

“I hate that we even have to make that determination,” MS. Dusang said. Lately, staff members have been pulling out some patients already in the ER’s rooms when others arrive who are more critically ill. “No one likes to take someone out of the privacy of their room and say, ‘We’re going to put you in a hallway because we need to get care to someone else.’”

ER patients have grown sicker

“We are hearing from members in every part of the country,” said Dr. Lisa Moreno, president of the American Academy of Emergency Medicine. “The Midwest, the South, the Northeast, the West … they are seeing this exact same phenomenon.”

Although the number of ER visits returned to pre-COVID levels this summer, admission rates, from the ER to the hospital’s inpatient floors, are still almost 20% higher. That’s according to the most recent analysis by the Epic Health Research Network, which pulls data from more than 120 million patients across the country.

“It’s an early indicator that what’s happening in the ED is that we’re seeing more acute cases than we were pre-pandemic,” said Caleb Cox, a data scientist at Epic.

Less acute cases, such as people with health issues like rashes or conjunctivitis, still aren’t going to the ER as much as they used to. Instead, they may be opting for an urgent care center or their primary care doctor, Mr. Cox explained. Meanwhile, there has been an increase in people coming to the ER with more serious conditions, like strokes and heart attacks.

So, even though the total number of patients coming to ERs is about the same as before the pandemic, “that’s absolutely going to feel like [if I’m an ER doctor or nurse] I’m seeing more patients and I’m seeing more acute patients,” Mr. Cox said.

Dr. Moreno, the AAEM president, works at an emergency department in New Orleans. She said the level of illness, and the inability to admit patients quickly and move them to beds upstairs, has created a level of chaos she described as “not even humane.”

At the beginning of a recent shift, she heard a patient crying nearby and went to investigate. It was a paraplegic man who’d recently had surgery for colon cancer. His large post-operative wound was sealed with a device called a wound vac, which pulls fluid from the wound into a drainage tube attached to a portable vacuum pump.

But the wound vac had malfunctioned, which is why he had come to the ER. Staffers were so busy, however, that by the time Dr. Moreno came in, the fluid from his wound was leaking everywhere.

“When I went in, the bed was covered,” she recalled. “I mean, he was lying in a puddle of secretions from this wound. And he was crying, because he said to me, ‘I’m paralyzed. I can’t move to get away from all these secretions, and I know I’m going to end up getting an infection. I know I’m going to end up getting an ulcer. I’ve been laying in this for, like, eight or nine hours.’”

The nurse in charge of his care told Dr. Moreno she simply hadn’t had time to help this patient yet. “She said, ‘I’ve had so many patients to take care of, and so many critical patients. I started [an IV] drip on this person. This person is on a cardiac monitor. I just didn’t have time to get in there.’”

“This is not humane care,” Dr. Moreno said. “This is horrible care.”

But it’s what can happen when emergency department staffers don’t have the resources they need to deal with the onslaught of competing demands.

“All the nurses and doctors had the highest level of intent to do the right thing for the person,” Dr. Moreno said. “But because of the high acuity of … a large number of patients, the staffing ratio of nurse to patient, even the staffing ratio of doctor to patient, this guy did not get the care that he deserved to get, just as a human being.”

The instance of unintended neglect that Dr. Moreno saw is extreme, and not the experience of most patients who arrive at ERs these days. But the problem is not new: Even before the pandemic, ER overcrowding had been a “widespread problem and a source of patient harm, according to a recent commentary in NEJM Catalyst Innovations in Care Delivery.

“ED crowding is not an issue of inconvenience,” the authors wrote. “There is incontrovertible evidence that ED crowding leads to significant patient harm, including morbidity and mortality related to consequential delays of treatment for both high- and low-acuity patients.”

And already-overwhelmed staffers are burning out.

Burnout feeds staffing shortages, and vice versa

Every morning, Tiffani Dusang wakes up and checks her Sparrow email with one singular hope: that she will not see yet another nurse resignation letter in her inbox.

“I cannot tell you how many of them [the nurses] tell me they went home crying” after their shifts, she said.

Despite Ms. Dusang’s best efforts to support her staffers, they’re leaving too fast to be replaced, either to take higher-paying gigs as a travel nurse, to try a less-stressful type of nursing, or simply walking away from the profession entirely.

Kelly Spitz has been an emergency department nurse at Sparrow for 10 years. But, lately, she has also fantasized about leaving. “It has crossed my mind several times,” she said, and yet she continues to come back. “Because I have a team here. And I love what I do.” But then she started to cry. The issue is not the hard work, or even the stress. She struggles with not being able to give her patients the kind of care and attention she wants to give them, and that they need and deserve, she said.

She often thinks about a patient whose test results revealed terminal cancer, she said. Ms. Spitz spent all day working the phones, hustling case managers, trying to get hospice care set up in the man’s home. He was going to die, and she just didn’t want him to have to die in the hospital, where only one visitor was allowed. She wanted to get him home, and back with his family.

Finally, after many hours, they found an ambulance to take him home.

Three days later, the man’s family members called Ms. Spitz: He had died surrounded by family. They were calling to thank her.

“I felt like I did my job there, because I got him home,” she said. But that’s a rare feeling these days. “I just hope it gets better. I hope it gets better soon.”

Around 4 p.m. at Sparrow Hospital as one shift approached its end, Ms. Dusang faced a new crisis: The overnight shift was more short-staffed than usual.

“Can we get two inpatient nurses?” she asked, hoping to borrow two nurses from one of the hospital floors upstairs.

“Already tried,” replied nurse Troy Latunski.

Without more staff, it’s going to be hard to care for new patients who come in overnight — from car crashes to seizures or other emergencies.

But Mr. Latunski had a plan: He would go home, snatch a few hours of sleep and return at 11 p.m. to work the overnight shift in the ER’s overflow unit. That meant he would be largely caring for eight patients, alone. On just a few short hours of sleep. But lately that seemed to be their only, and best, option.

Ms. Dusang considered for a moment, took a deep breath and nodded. “OK,” she said.

“Go home. Get some sleep. Thank you,” she added, shooting Mr. Latunski a grateful smile. And then she pivoted, because another nurse was approaching with an urgent question. On to the next crisis.

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. This story is part of a partnership that includes Michigan Radio, NPR and KHN.

Inside the emergency department at Sparrow Hospital in Lansing, Mich., staff members are struggling to care for patients showing up much sicker than they’ve ever seen.

Tiffani Dusang, the ER’s nursing director, practically vibrates with pent-up anxiety, looking at patients lying on a long line of stretchers pushed up against the beige walls of the hospital hallways. “It’s hard to watch,” she said in a warm Texas twang.

But there’s nothing she can do. The ER’s 72 rooms are already filled.

“I always feel very, very bad when I walk down the hallway and see that people are in pain, or needing to sleep, or needing quiet. But they have to be in the hallway with, as you can see, 10 or 15 people walking by every minute,” Ms. Dusang said.

The scene is a stark contrast to where this emergency department — and thousands of others — were at the start of the pandemic. Except for initial hot spots like New York City, in spring 2020 many ERs across the country were often eerily empty. Terrified of contracting COVID-19, people who were sick with other things did their best to stay away from hospitals. Visits to emergency rooms dropped to half their typical levels, according to the Epic Health Research Network, and didn’t fully rebound until this summer.

But now, they’re too full. Even in parts of the country where covid isn’t overwhelming the health system, patients are showing up to the ER sicker than before the pandemic, their diseases more advanced and in need of more complicated care.

Months of treatment delays have exacerbated chronic conditions and worsened symptoms. Doctors and nurses say the severity of illness ranges widely and includes abdominal pain, respiratory problems, blood clots, heart conditions and suicide attempts, among other conditions.

But they can hardly be accommodated. Emergency departments, ideally, are meant to be brief ports in a storm, with patients staying just long enough to be sent home with instructions to follow up with primary care physicians, or sufficiently stabilized to be transferred “upstairs” to inpatient or intensive care units.

Except now those long-term care floors are full too, with a mix of covid and non-covid patients. People coming to the ER get warehoused for hours, even days, forcing ER staffers to perform long-term care roles they weren’t trained to do.

At Sparrow, space is a valuable commodity in the ER: A separate section of the hospital was turned into an overflow unit. Stretchers stack up in halls. A row of brown reclining chairs lines a wall, intended for patients who aren’t sick enough for a stretcher but are too sick to stay in the main waiting room.

Forget privacy, Alejos Perrientoz learned when he arrived. He came to the ER because his arm had been tingling and painful for over a week. He couldn’t hold a cup of coffee. A nurse gave him a full physical exam in a brown recliner, which made him self-conscious about having his shirt lifted in front of strangers. “I felt a little uncomfortable,” he whispered. “But I have no choice, you know? I’m in the hallway. There’s no rooms.

“We could have done the physical in the parking lot,” he added, managing a laugh.

Even patients who arrive by ambulance are not guaranteed a room: One nurse runs triage, screening those who absolutely need a bed, and those who can be put in the waiting area.

“I hate that we even have to make that determination,” MS. Dusang said. Lately, staff members have been pulling out some patients already in the ER’s rooms when others arrive who are more critically ill. “No one likes to take someone out of the privacy of their room and say, ‘We’re going to put you in a hallway because we need to get care to someone else.’”

ER patients have grown sicker

“We are hearing from members in every part of the country,” said Dr. Lisa Moreno, president of the American Academy of Emergency Medicine. “The Midwest, the South, the Northeast, the West … they are seeing this exact same phenomenon.”

Although the number of ER visits returned to pre-COVID levels this summer, admission rates, from the ER to the hospital’s inpatient floors, are still almost 20% higher. That’s according to the most recent analysis by the Epic Health Research Network, which pulls data from more than 120 million patients across the country.

“It’s an early indicator that what’s happening in the ED is that we’re seeing more acute cases than we were pre-pandemic,” said Caleb Cox, a data scientist at Epic.

Less acute cases, such as people with health issues like rashes or conjunctivitis, still aren’t going to the ER as much as they used to. Instead, they may be opting for an urgent care center or their primary care doctor, Mr. Cox explained. Meanwhile, there has been an increase in people coming to the ER with more serious conditions, like strokes and heart attacks.

So, even though the total number of patients coming to ERs is about the same as before the pandemic, “that’s absolutely going to feel like [if I’m an ER doctor or nurse] I’m seeing more patients and I’m seeing more acute patients,” Mr. Cox said.

Dr. Moreno, the AAEM president, works at an emergency department in New Orleans. She said the level of illness, and the inability to admit patients quickly and move them to beds upstairs, has created a level of chaos she described as “not even humane.”

At the beginning of a recent shift, she heard a patient crying nearby and went to investigate. It was a paraplegic man who’d recently had surgery for colon cancer. His large post-operative wound was sealed with a device called a wound vac, which pulls fluid from the wound into a drainage tube attached to a portable vacuum pump.

But the wound vac had malfunctioned, which is why he had come to the ER. Staffers were so busy, however, that by the time Dr. Moreno came in, the fluid from his wound was leaking everywhere.

“When I went in, the bed was covered,” she recalled. “I mean, he was lying in a puddle of secretions from this wound. And he was crying, because he said to me, ‘I’m paralyzed. I can’t move to get away from all these secretions, and I know I’m going to end up getting an infection. I know I’m going to end up getting an ulcer. I’ve been laying in this for, like, eight or nine hours.’”

The nurse in charge of his care told Dr. Moreno she simply hadn’t had time to help this patient yet. “She said, ‘I’ve had so many patients to take care of, and so many critical patients. I started [an IV] drip on this person. This person is on a cardiac monitor. I just didn’t have time to get in there.’”

“This is not humane care,” Dr. Moreno said. “This is horrible care.”

But it’s what can happen when emergency department staffers don’t have the resources they need to deal with the onslaught of competing demands.

“All the nurses and doctors had the highest level of intent to do the right thing for the person,” Dr. Moreno said. “But because of the high acuity of … a large number of patients, the staffing ratio of nurse to patient, even the staffing ratio of doctor to patient, this guy did not get the care that he deserved to get, just as a human being.”

The instance of unintended neglect that Dr. Moreno saw is extreme, and not the experience of most patients who arrive at ERs these days. But the problem is not new: Even before the pandemic, ER overcrowding had been a “widespread problem and a source of patient harm, according to a recent commentary in NEJM Catalyst Innovations in Care Delivery.

“ED crowding is not an issue of inconvenience,” the authors wrote. “There is incontrovertible evidence that ED crowding leads to significant patient harm, including morbidity and mortality related to consequential delays of treatment for both high- and low-acuity patients.”

And already-overwhelmed staffers are burning out.

Burnout feeds staffing shortages, and vice versa

Every morning, Tiffani Dusang wakes up and checks her Sparrow email with one singular hope: that she will not see yet another nurse resignation letter in her inbox.

“I cannot tell you how many of them [the nurses] tell me they went home crying” after their shifts, she said.

Despite Ms. Dusang’s best efforts to support her staffers, they’re leaving too fast to be replaced, either to take higher-paying gigs as a travel nurse, to try a less-stressful type of nursing, or simply walking away from the profession entirely.

Kelly Spitz has been an emergency department nurse at Sparrow for 10 years. But, lately, she has also fantasized about leaving. “It has crossed my mind several times,” she said, and yet she continues to come back. “Because I have a team here. And I love what I do.” But then she started to cry. The issue is not the hard work, or even the stress. She struggles with not being able to give her patients the kind of care and attention she wants to give them, and that they need and deserve, she said.

She often thinks about a patient whose test results revealed terminal cancer, she said. Ms. Spitz spent all day working the phones, hustling case managers, trying to get hospice care set up in the man’s home. He was going to die, and she just didn’t want him to have to die in the hospital, where only one visitor was allowed. She wanted to get him home, and back with his family.

Finally, after many hours, they found an ambulance to take him home.

Three days later, the man’s family members called Ms. Spitz: He had died surrounded by family. They were calling to thank her.

“I felt like I did my job there, because I got him home,” she said. But that’s a rare feeling these days. “I just hope it gets better. I hope it gets better soon.”

Around 4 p.m. at Sparrow Hospital as one shift approached its end, Ms. Dusang faced a new crisis: The overnight shift was more short-staffed than usual.

“Can we get two inpatient nurses?” she asked, hoping to borrow two nurses from one of the hospital floors upstairs.

“Already tried,” replied nurse Troy Latunski.

Without more staff, it’s going to be hard to care for new patients who come in overnight — from car crashes to seizures or other emergencies.

But Mr. Latunski had a plan: He would go home, snatch a few hours of sleep and return at 11 p.m. to work the overnight shift in the ER’s overflow unit. That meant he would be largely caring for eight patients, alone. On just a few short hours of sleep. But lately that seemed to be their only, and best, option.

Ms. Dusang considered for a moment, took a deep breath and nodded. “OK,” she said.

“Go home. Get some sleep. Thank you,” she added, shooting Mr. Latunski a grateful smile. And then she pivoted, because another nurse was approaching with an urgent question. On to the next crisis.

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. This story is part of a partnership that includes Michigan Radio, NPR and KHN.

Inside the emergency department at Sparrow Hospital in Lansing, Mich., staff members are struggling to care for patients showing up much sicker than they’ve ever seen.

Tiffani Dusang, the ER’s nursing director, practically vibrates with pent-up anxiety, looking at patients lying on a long line of stretchers pushed up against the beige walls of the hospital hallways. “It’s hard to watch,” she said in a warm Texas twang.

But there’s nothing she can do. The ER’s 72 rooms are already filled.

“I always feel very, very bad when I walk down the hallway and see that people are in pain, or needing to sleep, or needing quiet. But they have to be in the hallway with, as you can see, 10 or 15 people walking by every minute,” Ms. Dusang said.

The scene is a stark contrast to where this emergency department — and thousands of others — were at the start of the pandemic. Except for initial hot spots like New York City, in spring 2020 many ERs across the country were often eerily empty. Terrified of contracting COVID-19, people who were sick with other things did their best to stay away from hospitals. Visits to emergency rooms dropped to half their typical levels, according to the Epic Health Research Network, and didn’t fully rebound until this summer.

But now, they’re too full. Even in parts of the country where covid isn’t overwhelming the health system, patients are showing up to the ER sicker than before the pandemic, their diseases more advanced and in need of more complicated care.

Months of treatment delays have exacerbated chronic conditions and worsened symptoms. Doctors and nurses say the severity of illness ranges widely and includes abdominal pain, respiratory problems, blood clots, heart conditions and suicide attempts, among other conditions.

But they can hardly be accommodated. Emergency departments, ideally, are meant to be brief ports in a storm, with patients staying just long enough to be sent home with instructions to follow up with primary care physicians, or sufficiently stabilized to be transferred “upstairs” to inpatient or intensive care units.

Except now those long-term care floors are full too, with a mix of covid and non-covid patients. People coming to the ER get warehoused for hours, even days, forcing ER staffers to perform long-term care roles they weren’t trained to do.

At Sparrow, space is a valuable commodity in the ER: A separate section of the hospital was turned into an overflow unit. Stretchers stack up in halls. A row of brown reclining chairs lines a wall, intended for patients who aren’t sick enough for a stretcher but are too sick to stay in the main waiting room.

Forget privacy, Alejos Perrientoz learned when he arrived. He came to the ER because his arm had been tingling and painful for over a week. He couldn’t hold a cup of coffee. A nurse gave him a full physical exam in a brown recliner, which made him self-conscious about having his shirt lifted in front of strangers. “I felt a little uncomfortable,” he whispered. “But I have no choice, you know? I’m in the hallway. There’s no rooms.

“We could have done the physical in the parking lot,” he added, managing a laugh.

Even patients who arrive by ambulance are not guaranteed a room: One nurse runs triage, screening those who absolutely need a bed, and those who can be put in the waiting area.

“I hate that we even have to make that determination,” MS. Dusang said. Lately, staff members have been pulling out some patients already in the ER’s rooms when others arrive who are more critically ill. “No one likes to take someone out of the privacy of their room and say, ‘We’re going to put you in a hallway because we need to get care to someone else.’”

ER patients have grown sicker

“We are hearing from members in every part of the country,” said Dr. Lisa Moreno, president of the American Academy of Emergency Medicine. “The Midwest, the South, the Northeast, the West … they are seeing this exact same phenomenon.”

Although the number of ER visits returned to pre-COVID levels this summer, admission rates, from the ER to the hospital’s inpatient floors, are still almost 20% higher. That’s according to the most recent analysis by the Epic Health Research Network, which pulls data from more than 120 million patients across the country.

“It’s an early indicator that what’s happening in the ED is that we’re seeing more acute cases than we were pre-pandemic,” said Caleb Cox, a data scientist at Epic.

Less acute cases, such as people with health issues like rashes or conjunctivitis, still aren’t going to the ER as much as they used to. Instead, they may be opting for an urgent care center or their primary care doctor, Mr. Cox explained. Meanwhile, there has been an increase in people coming to the ER with more serious conditions, like strokes and heart attacks.

So, even though the total number of patients coming to ERs is about the same as before the pandemic, “that’s absolutely going to feel like [if I’m an ER doctor or nurse] I’m seeing more patients and I’m seeing more acute patients,” Mr. Cox said.

Dr. Moreno, the AAEM president, works at an emergency department in New Orleans. She said the level of illness, and the inability to admit patients quickly and move them to beds upstairs, has created a level of chaos she described as “not even humane.”

At the beginning of a recent shift, she heard a patient crying nearby and went to investigate. It was a paraplegic man who’d recently had surgery for colon cancer. His large post-operative wound was sealed with a device called a wound vac, which pulls fluid from the wound into a drainage tube attached to a portable vacuum pump.

But the wound vac had malfunctioned, which is why he had come to the ER. Staffers were so busy, however, that by the time Dr. Moreno came in, the fluid from his wound was leaking everywhere.

“When I went in, the bed was covered,” she recalled. “I mean, he was lying in a puddle of secretions from this wound. And he was crying, because he said to me, ‘I’m paralyzed. I can’t move to get away from all these secretions, and I know I’m going to end up getting an infection. I know I’m going to end up getting an ulcer. I’ve been laying in this for, like, eight or nine hours.’”

The nurse in charge of his care told Dr. Moreno she simply hadn’t had time to help this patient yet. “She said, ‘I’ve had so many patients to take care of, and so many critical patients. I started [an IV] drip on this person. This person is on a cardiac monitor. I just didn’t have time to get in there.’”

“This is not humane care,” Dr. Moreno said. “This is horrible care.”

But it’s what can happen when emergency department staffers don’t have the resources they need to deal with the onslaught of competing demands.

“All the nurses and doctors had the highest level of intent to do the right thing for the person,” Dr. Moreno said. “But because of the high acuity of … a large number of patients, the staffing ratio of nurse to patient, even the staffing ratio of doctor to patient, this guy did not get the care that he deserved to get, just as a human being.”

The instance of unintended neglect that Dr. Moreno saw is extreme, and not the experience of most patients who arrive at ERs these days. But the problem is not new: Even before the pandemic, ER overcrowding had been a “widespread problem and a source of patient harm, according to a recent commentary in NEJM Catalyst Innovations in Care Delivery.

“ED crowding is not an issue of inconvenience,” the authors wrote. “There is incontrovertible evidence that ED crowding leads to significant patient harm, including morbidity and mortality related to consequential delays of treatment for both high- and low-acuity patients.”

And already-overwhelmed staffers are burning out.

Burnout feeds staffing shortages, and vice versa

Every morning, Tiffani Dusang wakes up and checks her Sparrow email with one singular hope: that she will not see yet another nurse resignation letter in her inbox.

“I cannot tell you how many of them [the nurses] tell me they went home crying” after their shifts, she said.

Despite Ms. Dusang’s best efforts to support her staffers, they’re leaving too fast to be replaced, either to take higher-paying gigs as a travel nurse, to try a less-stressful type of nursing, or simply walking away from the profession entirely.

Kelly Spitz has been an emergency department nurse at Sparrow for 10 years. But, lately, she has also fantasized about leaving. “It has crossed my mind several times,” she said, and yet she continues to come back. “Because I have a team here. And I love what I do.” But then she started to cry. The issue is not the hard work, or even the stress. She struggles with not being able to give her patients the kind of care and attention she wants to give them, and that they need and deserve, she said.

She often thinks about a patient whose test results revealed terminal cancer, she said. Ms. Spitz spent all day working the phones, hustling case managers, trying to get hospice care set up in the man’s home. He was going to die, and she just didn’t want him to have to die in the hospital, where only one visitor was allowed. She wanted to get him home, and back with his family.

Finally, after many hours, they found an ambulance to take him home.

Three days later, the man’s family members called Ms. Spitz: He had died surrounded by family. They were calling to thank her.

“I felt like I did my job there, because I got him home,” she said. But that’s a rare feeling these days. “I just hope it gets better. I hope it gets better soon.”

Around 4 p.m. at Sparrow Hospital as one shift approached its end, Ms. Dusang faced a new crisis: The overnight shift was more short-staffed than usual.

“Can we get two inpatient nurses?” she asked, hoping to borrow two nurses from one of the hospital floors upstairs.

“Already tried,” replied nurse Troy Latunski.

Without more staff, it’s going to be hard to care for new patients who come in overnight — from car crashes to seizures or other emergencies.

But Mr. Latunski had a plan: He would go home, snatch a few hours of sleep and return at 11 p.m. to work the overnight shift in the ER’s overflow unit. That meant he would be largely caring for eight patients, alone. On just a few short hours of sleep. But lately that seemed to be their only, and best, option.

Ms. Dusang considered for a moment, took a deep breath and nodded. “OK,” she said.

“Go home. Get some sleep. Thank you,” she added, shooting Mr. Latunski a grateful smile. And then she pivoted, because another nurse was approaching with an urgent question. On to the next crisis.

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. This story is part of a partnership that includes Michigan Radio, NPR and KHN.

Sigmoid colon perforation secondary to transcutaneous epicardial pacer wires.

A plain film image (Figure A) shows diffusely dilated loops of bowel with subdiaphragmatic air concerning for GI viscous perforation. Dedicated cross-sectional imaging confirms intra-abdominal free air, and in representative cross section, the epicardial pacing wires can be visualized within the gastrointestinal lumen (Figure D, arrows). At the time of surgical consultation, the radiology report was notable for concern regarding possible disruption of peritoneum secondary to the difficult surgical chest tube placement in a patient with a high-riding left hemidiaphragm. Urgent laparoscopic exploration secondary to these findings unexpectedly revealed that the transcutaneous epicardial pacing wires had been inadvertently placed through the sigmoid colon (Figure C). The pacer wires were cut and removed intraoperatively. Unfortunately, 4 days after removal of pacer wires, the patient continued to have ongoing distension and was found to have sigmoid volvulus necessitating endoscopic decompression. After a prolonged hospitalization and recovery, he was discharged with a normal bowel pattern and tolerating oral intake to a skilled nursing facility.

Temporary transcutaneous epicardial pacing wires are often placed after complex cardiovascular surgical procedures. Complications from wire placement are thought to be relatively rare and are typically associated with migration into local structures after wire placement and infectious complications secondary to retained wires.^1,2 Perforation of local structures during placement is less common, and GI viscous perforation in particular is not a well-characterized cause of associated morbidity.³

Our case demonstrates that, in patients with hemidiaphragm elevation, epicardial wire placement risks GI viscous perforation. Furthermore, given the frequency of concomitant surgical hardware in this patient population, identification of malpositioned epicardial wires on plain film and even cross-sectional imaging can be difficult and can delay diagnosis.

References

1. Del Nido P, Goldman BS. J Card Surg. 1989 Mar;4(1):99-103.

2. Kapoor A et al. Interact Cardiovasc Thorac Surg. 2011 Jul;13(1):104-6.

3. Haba J et al. Can Assoc Radiol J. 2013 Feb;64(1):77-80.

Sigmoid colon perforation secondary to transcutaneous epicardial pacer wires.

A plain film image (Figure A) shows diffusely dilated loops of bowel with subdiaphragmatic air concerning for GI viscous perforation. Dedicated cross-sectional imaging confirms intra-abdominal free air, and in representative cross section, the epicardial pacing wires can be visualized within the gastrointestinal lumen (Figure D, arrows). At the time of surgical consultation, the radiology report was notable for concern regarding possible disruption of peritoneum secondary to the difficult surgical chest tube placement in a patient with a high-riding left hemidiaphragm. Urgent laparoscopic exploration secondary to these findings unexpectedly revealed that the transcutaneous epicardial pacing wires had been inadvertently placed through the sigmoid colon (Figure C). The pacer wires were cut and removed intraoperatively. Unfortunately, 4 days after removal of pacer wires, the patient continued to have ongoing distension and was found to have sigmoid volvulus necessitating endoscopic decompression. After a prolonged hospitalization and recovery, he was discharged with a normal bowel pattern and tolerating oral intake to a skilled nursing facility.

Temporary transcutaneous epicardial pacing wires are often placed after complex cardiovascular surgical procedures. Complications from wire placement are thought to be relatively rare and are typically associated with migration into local structures after wire placement and infectious complications secondary to retained wires.^1,2 Perforation of local structures during placement is less common, and GI viscous perforation in particular is not a well-characterized cause of associated morbidity.³

Our case demonstrates that, in patients with hemidiaphragm elevation, epicardial wire placement risks GI viscous perforation. Furthermore, given the frequency of concomitant surgical hardware in this patient population, identification of malpositioned epicardial wires on plain film and even cross-sectional imaging can be difficult and can delay diagnosis.

References

1. Del Nido P, Goldman BS. J Card Surg. 1989 Mar;4(1):99-103.

2. Kapoor A et al. Interact Cardiovasc Thorac Surg. 2011 Jul;13(1):104-6.

3. Haba J et al. Can Assoc Radiol J. 2013 Feb;64(1):77-80.

Sigmoid colon perforation secondary to transcutaneous epicardial pacer wires.

A plain film image (Figure A) shows diffusely dilated loops of bowel with subdiaphragmatic air concerning for GI viscous perforation. Dedicated cross-sectional imaging confirms intra-abdominal free air, and in representative cross section, the epicardial pacing wires can be visualized within the gastrointestinal lumen (Figure D, arrows). At the time of surgical consultation, the radiology report was notable for concern regarding possible disruption of peritoneum secondary to the difficult surgical chest tube placement in a patient with a high-riding left hemidiaphragm. Urgent laparoscopic exploration secondary to these findings unexpectedly revealed that the transcutaneous epicardial pacing wires had been inadvertently placed through the sigmoid colon (Figure C). The pacer wires were cut and removed intraoperatively. Unfortunately, 4 days after removal of pacer wires, the patient continued to have ongoing distension and was found to have sigmoid volvulus necessitating endoscopic decompression. After a prolonged hospitalization and recovery, he was discharged with a normal bowel pattern and tolerating oral intake to a skilled nursing facility.

Temporary transcutaneous epicardial pacing wires are often placed after complex cardiovascular surgical procedures. Complications from wire placement are thought to be relatively rare and are typically associated with migration into local structures after wire placement and infectious complications secondary to retained wires.^1,2 Perforation of local structures during placement is less common, and GI viscous perforation in particular is not a well-characterized cause of associated morbidity.³

Our case demonstrates that, in patients with hemidiaphragm elevation, epicardial wire placement risks GI viscous perforation. Furthermore, given the frequency of concomitant surgical hardware in this patient population, identification of malpositioned epicardial wires on plain film and even cross-sectional imaging can be difficult and can delay diagnosis.

References

1. Del Nido P, Goldman BS. J Card Surg. 1989 Mar;4(1):99-103.

2. Kapoor A et al. Interact Cardiovasc Thorac Surg. 2011 Jul;13(1):104-6.

3. Haba J et al. Can Assoc Radiol J. 2013 Feb;64(1):77-80.

My office’s storage room has an old bankers box, which has been there since I moved 8 years ago. Before that it was at my other office, behind an old desk. I had no idea what was in it, I always assumed office supplies, surplus drug company pens and sticky notes, who-knows-whats.

Last week I had one of those days where everyone cancels, so I decided to investigate the box.

It was packed with 10 years worth (2000-2010) of my secretary’s MRI scheduling sheets that had somehow escaped occasional shredding purges. So I sat down next to the office shredder to get rid of them.

As I fed the sheets in, the names jumped out at me. Some I have absolutely no recollection of. Others I still see today.

There were names of the long-deceased, bringing them back to me for the first time in years. There were others that I have no idea what happened to – they must have just stopped seeing me at some point, though for the life of me I can’t remember when, or why. Yet, in my mind, there they were, as if I’d just seen them yesterday. A few times I got curious enough to turn back to my computer and look up their charts, trying to remember their stories.

Then there were those I still remember clearly, every single detail of, in spite of the elapsed time. Something about their case or personality had indelibly etched them in my memory. A valuable lesson learned from them that had something or nothing to do with medicine that’s still with me.

Looking back, I’d guess I’ve seen roughly 15,000-20,000 patients over my career. Not nearly as many as my colleagues in general practice, but still quite a few. A decent sized basketball arena full.

The majority don’t stick with you. That’s the way it is in life. We meet a lot of people as we walk down the road, but generally only remember those walking with us for a good part of it.

The ones we didn’t know long – but who are still clearly remembered – are also valuable. In their own way, perhaps unknowingly, they made an impact that hopefully makes us better.

For that I’ll always be grateful to them.

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

My office’s storage room has an old bankers box, which has been there since I moved 8 years ago. Before that it was at my other office, behind an old desk. I had no idea what was in it, I always assumed office supplies, surplus drug company pens and sticky notes, who-knows-whats.

Last week I had one of those days where everyone cancels, so I decided to investigate the box.

It was packed with 10 years worth (2000-2010) of my secretary’s MRI scheduling sheets that had somehow escaped occasional shredding purges. So I sat down next to the office shredder to get rid of them.

As I fed the sheets in, the names jumped out at me. Some I have absolutely no recollection of. Others I still see today.

There were names of the long-deceased, bringing them back to me for the first time in years. There were others that I have no idea what happened to – they must have just stopped seeing me at some point, though for the life of me I can’t remember when, or why. Yet, in my mind, there they were, as if I’d just seen them yesterday. A few times I got curious enough to turn back to my computer and look up their charts, trying to remember their stories.

Then there were those I still remember clearly, every single detail of, in spite of the elapsed time. Something about their case or personality had indelibly etched them in my memory. A valuable lesson learned from them that had something or nothing to do with medicine that’s still with me.

Looking back, I’d guess I’ve seen roughly 15,000-20,000 patients over my career. Not nearly as many as my colleagues in general practice, but still quite a few. A decent sized basketball arena full.

The majority don’t stick with you. That’s the way it is in life. We meet a lot of people as we walk down the road, but generally only remember those walking with us for a good part of it.

The ones we didn’t know long – but who are still clearly remembered – are also valuable. In their own way, perhaps unknowingly, they made an impact that hopefully makes us better.

For that I’ll always be grateful to them.

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

My office’s storage room has an old bankers box, which has been there since I moved 8 years ago. Before that it was at my other office, behind an old desk. I had no idea what was in it, I always assumed office supplies, surplus drug company pens and sticky notes, who-knows-whats.

Last week I had one of those days where everyone cancels, so I decided to investigate the box.

It was packed with 10 years worth (2000-2010) of my secretary’s MRI scheduling sheets that had somehow escaped occasional shredding purges. So I sat down next to the office shredder to get rid of them.

As I fed the sheets in, the names jumped out at me. Some I have absolutely no recollection of. Others I still see today.

There were names of the long-deceased, bringing them back to me for the first time in years. There were others that I have no idea what happened to – they must have just stopped seeing me at some point, though for the life of me I can’t remember when, or why. Yet, in my mind, there they were, as if I’d just seen them yesterday. A few times I got curious enough to turn back to my computer and look up their charts, trying to remember their stories.

Then there were those I still remember clearly, every single detail of, in spite of the elapsed time. Something about their case or personality had indelibly etched them in my memory. A valuable lesson learned from them that had something or nothing to do with medicine that’s still with me.

Looking back, I’d guess I’ve seen roughly 15,000-20,000 patients over my career. Not nearly as many as my colleagues in general practice, but still quite a few. A decent sized basketball arena full.

The majority don’t stick with you. That’s the way it is in life. We meet a lot of people as we walk down the road, but generally only remember those walking with us for a good part of it.

The ones we didn’t know long – but who are still clearly remembered – are also valuable. In their own way, perhaps unknowingly, they made an impact that hopefully makes us better.

For that I’ll always be grateful to them.

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

Nearly one in three gay and bisexual men who were diagnosed with HIV at U.K. sexual health clinics didn’t meet the criteria for “high risk” that would signal to a clinician that they would be good candidates for pre-exposure prophylaxis (PrEP).

And that means that people who appear lower risk may still be good candidates for the HIV prevention pills, said Ann Sullivan, MD, consulting physician at Chelsea and Westminster Hospital, London.

“If people are coming forward for PrEP, they have self-identified that they need PrEP, [and] we should be allowing them to take PrEP,” said Dr. Sullivan at the 18th European AIDS Society Conference (EACS 2021). “We just need to trust patients. People know their risk, and we just have to accept that they know what they need best.”

And while this trial was made up of 95% gay and bisexual men, that ethos applies to every other group that could benefit from PrEP, including cisgender and transgender women and other gender-diverse people, Latinos, and Black Americans. In the United States, these groups make up nearly half of those who could benefit from PrEP under older guidelines but account for just 8% of people currently taking PrEP.

The finding also reinforces growing calls from health care providers to reduce gatekeeping around PrEP. For instance, there’s a move underway by the U.S. Centers for Disease Control and Prevention, where drafts of updated PrEP guidelines call for clinicians to talk to any sexually active teenager and adult about PrEP.

For the PrEP Impact trial, gay and bisexual men who received sexual health care at UK National Health Service sexual health clinics were invited to enroll in the study based on national PrEP guidelines. Those guidelines included being a cisgender man who had had sex with men not currently living with HIV and reporting condomless anal sex in the last 3 months; having a male partner whose HIV status they don’t know or who doesn’t have an undetectable viral load and with whom they’ve had condomless anal sex; or someone who doesn’t reach those criteria but whom the clinician thinks would be a good candidate.

Between Oct. 2017 and Feb. 2020, a total of 17,770 gay and bisexual men and 503 transgender or nonbinary people enrolled in the trial and were paired with 97,098 gay and bisexual men who didn’t use PrEP. (Data from the transgender participants were reported in a separate presentation.) The median age was 27 years, with 14.4% of the cisgender gay men between the ages of 16 and 24. Three out of four cis men were White, most lived in London, and more than half came from very-low-income neighborhoods.

Participants and controls were assessed for whether they were at particularly high risk for acquiring HIV, such as having used PrEP, having had two or more HIV tests, having had a rectal bacterial sexually transmitted infection (STI), or having had contact with someone with HIV or syphilis.

At the end of Feb. 2020, 24 cisgender men on PrEP had acquired HIV compared with 670 in the control group – an 87% reduction in HIV acquisition. Only one of those 24 cis men had lab-confirmed high adherence to PrEP. However, because the hair samples used to judge drug concentration weren’t long enough, Dr. Sullivan and colleagues were unable to assess whether the person really was fully adherent to treatment for the length of the trial.

But when they looked at the assessed behavior of people who acquired HIV, the two groups diverged. While a full 92% of people using PrEP had had STI diagnoses and other markers of increased risk, that was true for only 71% of people not taking PrEP. That meant, Dr. Sullivan said in an interview, that screening guidelines for PrEP were missing 29% of people with low assessed risk for HIV who nevertheless acquired the virus.

The findings led Antonio Urbina, MD, who both prescribes PrEP and manages Mount Sinai Medical Center’s PrEP program in New York, to the same conclusion that Dr. Sullivan and her team came to: that no screener is going to account for everything, and that there may be things that patients don’t want to tell their clinicians about their risk, either because of their own internalized stigma or their calculation that they aren’t comfortable enough with their providers to be honest.

“It reinforces to me that I need to ask more open-ended questions regarding risk and then just talk more about PrEP,” said Dr. Urbina, professor of medicine at Icahn School of Medicine. “Risk is dynamic and changes. And the great thing about PrEP is that if the risk goes up or down, if you have PrEP on board, you maintain this protection against HIV.”

An accompanying presentation on the transgender and nonbinary participants in the Impact Trial found that just one of 503 PrEP users acquired HIV. But here, too, there were people who could have benefited from PrEP but didn’t take it: Of the 477 trans and nonbinary participants who acted as controls, 97 were eligible by current guidelines but didn’t take PrEP. One in four of those declined the offer to take PrEP; the rest weren’t able to take it because they lived outside the treatment area. That, combined with a significantly lower likelihood that Black trans and nonbinary people took PrEP, indicated that work needs to be done to address the needs of people geographically and ethnically.

The data on gay men also raised the “who’s left out” issue for Gina Simoncini, MD, medical director for the Philadelphia AIDS Healthcare Foundation Healthcare Center. Dr. Simoncini previously taught attending physicians at Temple University how to prescribe PrEP and has done many grand rounds for primary care providers on how to manage PrEP.

“My biggest issue with this data is: What about the people who aren’t going to sexual health clinics?” she said. “What about the kid who’s 16 and maybe just barely putting his feet into the waters of sex and doesn’t feel quite comfortable going to a sexual health clinic? What about the trans Indian girl who can’t get to sexual health clinics because of family stigma and cultural stigma? The more we move toward primary care, the more people need to get on board with this.”

Dr. Sullivan reports no relevant financial relationships. Dr. Simoncini is an employee of AIDS Healthcare Foundation and has received advisory board fees from ViiV Healthcare. Dr. Urbina sits on the scientific advisory councils for Gilead Sciences, ViiV Healthcare, and Merck.

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

Nearly one in three gay and bisexual men who were diagnosed with HIV at U.K. sexual health clinics didn’t meet the criteria for “high risk” that would signal to a clinician that they would be good candidates for pre-exposure prophylaxis (PrEP).

And that means that people who appear lower risk may still be good candidates for the HIV prevention pills, said Ann Sullivan, MD, consulting physician at Chelsea and Westminster Hospital, London.

“If people are coming forward for PrEP, they have self-identified that they need PrEP, [and] we should be allowing them to take PrEP,” said Dr. Sullivan at the 18th European AIDS Society Conference (EACS 2021). “We just need to trust patients. People know their risk, and we just have to accept that they know what they need best.”

And while this trial was made up of 95% gay and bisexual men, that ethos applies to every other group that could benefit from PrEP, including cisgender and transgender women and other gender-diverse people, Latinos, and Black Americans. In the United States, these groups make up nearly half of those who could benefit from PrEP under older guidelines but account for just 8% of people currently taking PrEP.

The finding also reinforces growing calls from health care providers to reduce gatekeeping around PrEP. For instance, there’s a move underway by the U.S. Centers for Disease Control and Prevention, where drafts of updated PrEP guidelines call for clinicians to talk to any sexually active teenager and adult about PrEP.

For the PrEP Impact trial, gay and bisexual men who received sexual health care at UK National Health Service sexual health clinics were invited to enroll in the study based on national PrEP guidelines. Those guidelines included being a cisgender man who had had sex with men not currently living with HIV and reporting condomless anal sex in the last 3 months; having a male partner whose HIV status they don’t know or who doesn’t have an undetectable viral load and with whom they’ve had condomless anal sex; or someone who doesn’t reach those criteria but whom the clinician thinks would be a good candidate.

Between Oct. 2017 and Feb. 2020, a total of 17,770 gay and bisexual men and 503 transgender or nonbinary people enrolled in the trial and were paired with 97,098 gay and bisexual men who didn’t use PrEP. (Data from the transgender participants were reported in a separate presentation.) The median age was 27 years, with 14.4% of the cisgender gay men between the ages of 16 and 24. Three out of four cis men were White, most lived in London, and more than half came from very-low-income neighborhoods.

Participants and controls were assessed for whether they were at particularly high risk for acquiring HIV, such as having used PrEP, having had two or more HIV tests, having had a rectal bacterial sexually transmitted infection (STI), or having had contact with someone with HIV or syphilis.

At the end of Feb. 2020, 24 cisgender men on PrEP had acquired HIV compared with 670 in the control group – an 87% reduction in HIV acquisition. Only one of those 24 cis men had lab-confirmed high adherence to PrEP. However, because the hair samples used to judge drug concentration weren’t long enough, Dr. Sullivan and colleagues were unable to assess whether the person really was fully adherent to treatment for the length of the trial.

But when they looked at the assessed behavior of people who acquired HIV, the two groups diverged. While a full 92% of people using PrEP had had STI diagnoses and other markers of increased risk, that was true for only 71% of people not taking PrEP. That meant, Dr. Sullivan said in an interview, that screening guidelines for PrEP were missing 29% of people with low assessed risk for HIV who nevertheless acquired the virus.

The findings led Antonio Urbina, MD, who both prescribes PrEP and manages Mount Sinai Medical Center’s PrEP program in New York, to the same conclusion that Dr. Sullivan and her team came to: that no screener is going to account for everything, and that there may be things that patients don’t want to tell their clinicians about their risk, either because of their own internalized stigma or their calculation that they aren’t comfortable enough with their providers to be honest.

“It reinforces to me that I need to ask more open-ended questions regarding risk and then just talk more about PrEP,” said Dr. Urbina, professor of medicine at Icahn School of Medicine. “Risk is dynamic and changes. And the great thing about PrEP is that if the risk goes up or down, if you have PrEP on board, you maintain this protection against HIV.”

An accompanying presentation on the transgender and nonbinary participants in the Impact Trial found that just one of 503 PrEP users acquired HIV. But here, too, there were people who could have benefited from PrEP but didn’t take it: Of the 477 trans and nonbinary participants who acted as controls, 97 were eligible by current guidelines but didn’t take PrEP. One in four of those declined the offer to take PrEP; the rest weren’t able to take it because they lived outside the treatment area. That, combined with a significantly lower likelihood that Black trans and nonbinary people took PrEP, indicated that work needs to be done to address the needs of people geographically and ethnically.

The data on gay men also raised the “who’s left out” issue for Gina Simoncini, MD, medical director for the Philadelphia AIDS Healthcare Foundation Healthcare Center. Dr. Simoncini previously taught attending physicians at Temple University how to prescribe PrEP and has done many grand rounds for primary care providers on how to manage PrEP.

“My biggest issue with this data is: What about the people who aren’t going to sexual health clinics?” she said. “What about the kid who’s 16 and maybe just barely putting his feet into the waters of sex and doesn’t feel quite comfortable going to a sexual health clinic? What about the trans Indian girl who can’t get to sexual health clinics because of family stigma and cultural stigma? The more we move toward primary care, the more people need to get on board with this.”

Dr. Sullivan reports no relevant financial relationships. Dr. Simoncini is an employee of AIDS Healthcare Foundation and has received advisory board fees from ViiV Healthcare. Dr. Urbina sits on the scientific advisory councils for Gilead Sciences, ViiV Healthcare, and Merck.

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

Nearly one in three gay and bisexual men who were diagnosed with HIV at U.K. sexual health clinics didn’t meet the criteria for “high risk” that would signal to a clinician that they would be good candidates for pre-exposure prophylaxis (PrEP).

And that means that people who appear lower risk may still be good candidates for the HIV prevention pills, said Ann Sullivan, MD, consulting physician at Chelsea and Westminster Hospital, London.

“If people are coming forward for PrEP, they have self-identified that they need PrEP, [and] we should be allowing them to take PrEP,” said Dr. Sullivan at the 18th European AIDS Society Conference (EACS 2021). “We just need to trust patients. People know their risk, and we just have to accept that they know what they need best.”

And while this trial was made up of 95% gay and bisexual men, that ethos applies to every other group that could benefit from PrEP, including cisgender and transgender women and other gender-diverse people, Latinos, and Black Americans. In the United States, these groups make up nearly half of those who could benefit from PrEP under older guidelines but account for just 8% of people currently taking PrEP.

The finding also reinforces growing calls from health care providers to reduce gatekeeping around PrEP. For instance, there’s a move underway by the U.S. Centers for Disease Control and Prevention, where drafts of updated PrEP guidelines call for clinicians to talk to any sexually active teenager and adult about PrEP.

For the PrEP Impact trial, gay and bisexual men who received sexual health care at UK National Health Service sexual health clinics were invited to enroll in the study based on national PrEP guidelines. Those guidelines included being a cisgender man who had had sex with men not currently living with HIV and reporting condomless anal sex in the last 3 months; having a male partner whose HIV status they don’t know or who doesn’t have an undetectable viral load and with whom they’ve had condomless anal sex; or someone who doesn’t reach those criteria but whom the clinician thinks would be a good candidate.

Between Oct. 2017 and Feb. 2020, a total of 17,770 gay and bisexual men and 503 transgender or nonbinary people enrolled in the trial and were paired with 97,098 gay and bisexual men who didn’t use PrEP. (Data from the transgender participants were reported in a separate presentation.) The median age was 27 years, with 14.4% of the cisgender gay men between the ages of 16 and 24. Three out of four cis men were White, most lived in London, and more than half came from very-low-income neighborhoods.

Participants and controls were assessed for whether they were at particularly high risk for acquiring HIV, such as having used PrEP, having had two or more HIV tests, having had a rectal bacterial sexually transmitted infection (STI), or having had contact with someone with HIV or syphilis.

At the end of Feb. 2020, 24 cisgender men on PrEP had acquired HIV compared with 670 in the control group – an 87% reduction in HIV acquisition. Only one of those 24 cis men had lab-confirmed high adherence to PrEP. However, because the hair samples used to judge drug concentration weren’t long enough, Dr. Sullivan and colleagues were unable to assess whether the person really was fully adherent to treatment for the length of the trial.

But when they looked at the assessed behavior of people who acquired HIV, the two groups diverged. While a full 92% of people using PrEP had had STI diagnoses and other markers of increased risk, that was true for only 71% of people not taking PrEP. That meant, Dr. Sullivan said in an interview, that screening guidelines for PrEP were missing 29% of people with low assessed risk for HIV who nevertheless acquired the virus.

The findings led Antonio Urbina, MD, who both prescribes PrEP and manages Mount Sinai Medical Center’s PrEP program in New York, to the same conclusion that Dr. Sullivan and her team came to: that no screener is going to account for everything, and that there may be things that patients don’t want to tell their clinicians about their risk, either because of their own internalized stigma or their calculation that they aren’t comfortable enough with their providers to be honest.

“It reinforces to me that I need to ask more open-ended questions regarding risk and then just talk more about PrEP,” said Dr. Urbina, professor of medicine at Icahn School of Medicine. “Risk is dynamic and changes. And the great thing about PrEP is that if the risk goes up or down, if you have PrEP on board, you maintain this protection against HIV.”

An accompanying presentation on the transgender and nonbinary participants in the Impact Trial found that just one of 503 PrEP users acquired HIV. But here, too, there were people who could have benefited from PrEP but didn’t take it: Of the 477 trans and nonbinary participants who acted as controls, 97 were eligible by current guidelines but didn’t take PrEP. One in four of those declined the offer to take PrEP; the rest weren’t able to take it because they lived outside the treatment area. That, combined with a significantly lower likelihood that Black trans and nonbinary people took PrEP, indicated that work needs to be done to address the needs of people geographically and ethnically.

The data on gay men also raised the “who’s left out” issue for Gina Simoncini, MD, medical director for the Philadelphia AIDS Healthcare Foundation Healthcare Center. Dr. Simoncini previously taught attending physicians at Temple University how to prescribe PrEP and has done many grand rounds for primary care providers on how to manage PrEP.

“My biggest issue with this data is: What about the people who aren’t going to sexual health clinics?” she said. “What about the kid who’s 16 and maybe just barely putting his feet into the waters of sex and doesn’t feel quite comfortable going to a sexual health clinic? What about the trans Indian girl who can’t get to sexual health clinics because of family stigma and cultural stigma? The more we move toward primary care, the more people need to get on board with this.”

Dr. Sullivan reports no relevant financial relationships. Dr. Simoncini is an employee of AIDS Healthcare Foundation and has received advisory board fees from ViiV Healthcare. Dr. Urbina sits on the scientific advisory councils for Gilead Sciences, ViiV Healthcare, and Merck.

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

One year into offering the first long-acting injectable HIV treatment to his patients, Jonathan Angel, MD, head of the division of infectious diseases at the University of Ottawa, reported that 15 of the 21 of patients who started on the regimen are still taking it, all with viral suppression. Those who weren’t cited a combination of inconvenience, injection site pain, and “injection fatigue.”

These are just a few things HIV providers are learning as they begin what Chloe Orkin, MD, professor of HIV medicine at Queen Mary University of London, called a paradigm shift to long-acting treatment, which may soon include not just shots but rings, implants, and microarray patches.

“It’s a paradigm shift, and we are at the very beginning of this paradigm shift,” said Dr. Orkin, commenting during the discussion session of the European AIDS Clinical Society 2021 annual meeting. “We’re having to change our model, and it’s challenging.”

In the United States, the Food and Drug Administration approved the first long-acting injectable, a combination of cabotegravir and rilpivirine (CAB/RIL; Cabenuva, ViiV Healthcare) in January 2021. But it has been approved in Canada since March 2020 and available at Dr. Angel’s clinic since November 2020. It’s also available in Canada as an every-other-month shot. Injected into the buttocks, the shot was found to be noninferior to standard daily oral treatment in many studies, including the ATLAS, the ATLAS-2M – which tested the every-other-month approach – and FLAIR trials.

Dr. Angel’s clinic was part of all three of those trials, so his clinic has had 5 years’ experience preparing for the change in workflow and the new approach the shots require.

Of the 21 people Dr. Angel has treated, 11 were white Canadians, nine were Black African, and one was Indigenous Canadian, with women making up a third of the participants. Median age was 51 years, and all patients had had undetectable viral loads before beginning the regimen. (Studies of the drug’s effectiveness in people who struggle to take daily pills are still ongoing.)

Most of those 21 patients had had undetectable viral loads for more than 5 years, but a few had been undetectable for only 6 months before beginning the shots. Their immune systems were also healthy, with a median CD4 count of 618 cells/mcL. As in the clinical trials, none of the participants had experienced antiretroviral treatment failure. Because public health insurers in Canada have yet to approve the shots, Dr. Angel’s patients receiving Cabenuva also have private health insurance. Up to 90% of people in Canada receive pharmaceutical coverage through public insurance; therefore, the shot is not yet widely available.

Twenty patients switched from integrase-inhibitor regimens, and one had been receiving a nonnucleoside reverse transcriptase inhibitor–based regimen before starting Cabenuva.

And although the drug has not been approved for shot initiation this way, two patients requested – and Dr. Angel agreed – to start them on the shots without first doing a month of daily pills to check for safety.

“This is my conclusion from these data: the oral lead-in period is not necessary,” Dr. Angel said in his presentation at the meeting. “It can provide some comfort to either a physician or a patient, but it does not seem to be medically necessary.”

That approach is not without data to back it up. Research presented at HIV Glasgow 2020 showed that people who switched from daily oral dolutegravir/abacavir/lamivudine straight to the injections did so without problems.

At last clinic visit, 15 of those 21 were still receiving the shots. None have experienced treatment failure, and all were still virally suppressed. Four participants left the trials and one more person opted to return to daily pills, citing some level of what Dr. Angel called “injection fatigue.”

“Just as we use the term ‘pill fatigue’ for patients who are tired of taking pills, patients do get tired of coming in monthly for their visits and injections,” he said. They find the trip to the clinic for the intramuscular injections “inconvenient,” he said.

Unlike in the United States, where Cabenuva is approved for only monthly injections, Health Canada has already approved the shot for every-other-month injections, which Dr. Angel said may reduce the odds of injection fatigue.

Dr. Angel’s presentation drew comments, questions, and excitement from the crowd. Annemarie Wensing, MD, assistant professor of medicine at University Medical Center Utrecht (the Netherlands), asked whether dispensing with the oral lead-in period could mean that these shots could be useful for people going on longer trips, people having surgeries where they can’t swallow pills, or in other scenarios.

“These are not hypothetical conversations,” Dr. Angel said. “I’m having these conversations with patients now – temporary use, they travel for 3 months and come back, can they go from injectable to oral to injectable.”

For now, he said, the answer is, “We’ll figure it out.”

Meanwhile, there’s another big question when it comes to injectables, said Marta Vas ylyev, MD, from Lviv (Ukraine) Regional AIDS Center: When will they be available to the people who might benefit most from them – people in resource-limited settings, people who so far have struggled to remember to take their pills every day?

For now, Dr. Angel replied, injectables continue to be a treatment only for those who are already doing well while receiving HIV treatment: those with already suppressed viral load, who are good at taking daily pills, and who are being treated at well-resourced clinics.

“There are huge obstacles to overcome if this is ever to be available [in resource-limited settings], and way more obstacles than there are with any oral therapies,” he said. “There’s not been much discussion here about the necessity of cold-chain requirements of pharmacies either centrally or locally, [or] the requirements of additional nurses or health care staff to administer the medication. So you’re looking at a very resource-intensive therapy, which now is fairly restrictive [as to] who will have access to it.”

Dr. Angel reports serving on advisory boards for ViiV Healthcare and Gilead Sciences and has done contract research for ViiV Healthcare, Gilead, and Merck. Dr. Orkin has received research grants, fees as a consultant, travel sponsorship, and speaker fees from ViiV, Merck, and GlaxoSmithKline. Dr. Vasylyev reported no relevant financial relationships.  

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

One year into offering the first long-acting injectable HIV treatment to his patients, Jonathan Angel, MD, head of the division of infectious diseases at the University of Ottawa, reported that 15 of the 21 of patients who started on the regimen are still taking it, all with viral suppression. Those who weren’t cited a combination of inconvenience, injection site pain, and “injection fatigue.”

These are just a few things HIV providers are learning as they begin what Chloe Orkin, MD, professor of HIV medicine at Queen Mary University of London, called a paradigm shift to long-acting treatment, which may soon include not just shots but rings, implants, and microarray patches.

“It’s a paradigm shift, and we are at the very beginning of this paradigm shift,” said Dr. Orkin, commenting during the discussion session of the European AIDS Clinical Society 2021 annual meeting. “We’re having to change our model, and it’s challenging.”

In the United States, the Food and Drug Administration approved the first long-acting injectable, a combination of cabotegravir and rilpivirine (CAB/RIL; Cabenuva, ViiV Healthcare) in January 2021. But it has been approved in Canada since March 2020 and available at Dr. Angel’s clinic since November 2020. It’s also available in Canada as an every-other-month shot. Injected into the buttocks, the shot was found to be noninferior to standard daily oral treatment in many studies, including the ATLAS, the ATLAS-2M – which tested the every-other-month approach – and FLAIR trials.

Dr. Angel’s clinic was part of all three of those trials, so his clinic has had 5 years’ experience preparing for the change in workflow and the new approach the shots require.

Of the 21 people Dr. Angel has treated, 11 were white Canadians, nine were Black African, and one was Indigenous Canadian, with women making up a third of the participants. Median age was 51 years, and all patients had had undetectable viral loads before beginning the regimen. (Studies of the drug’s effectiveness in people who struggle to take daily pills are still ongoing.)

Most of those 21 patients had had undetectable viral loads for more than 5 years, but a few had been undetectable for only 6 months before beginning the shots. Their immune systems were also healthy, with a median CD4 count of 618 cells/mcL. As in the clinical trials, none of the participants had experienced antiretroviral treatment failure. Because public health insurers in Canada have yet to approve the shots, Dr. Angel’s patients receiving Cabenuva also have private health insurance. Up to 90% of people in Canada receive pharmaceutical coverage through public insurance; therefore, the shot is not yet widely available.

Twenty patients switched from integrase-inhibitor regimens, and one had been receiving a nonnucleoside reverse transcriptase inhibitor–based regimen before starting Cabenuva.

And although the drug has not been approved for shot initiation this way, two patients requested – and Dr. Angel agreed – to start them on the shots without first doing a month of daily pills to check for safety.

“This is my conclusion from these data: the oral lead-in period is not necessary,” Dr. Angel said in his presentation at the meeting. “It can provide some comfort to either a physician or a patient, but it does not seem to be medically necessary.”

That approach is not without data to back it up. Research presented at HIV Glasgow 2020 showed that people who switched from daily oral dolutegravir/abacavir/lamivudine straight to the injections did so without problems.

At last clinic visit, 15 of those 21 were still receiving the shots. None have experienced treatment failure, and all were still virally suppressed. Four participants left the trials and one more person opted to return to daily pills, citing some level of what Dr. Angel called “injection fatigue.”

“Just as we use the term ‘pill fatigue’ for patients who are tired of taking pills, patients do get tired of coming in monthly for their visits and injections,” he said. They find the trip to the clinic for the intramuscular injections “inconvenient,” he said.

Unlike in the United States, where Cabenuva is approved for only monthly injections, Health Canada has already approved the shot for every-other-month injections, which Dr. Angel said may reduce the odds of injection fatigue.

Dr. Angel’s presentation drew comments, questions, and excitement from the crowd. Annemarie Wensing, MD, assistant professor of medicine at University Medical Center Utrecht (the Netherlands), asked whether dispensing with the oral lead-in period could mean that these shots could be useful for people going on longer trips, people having surgeries where they can’t swallow pills, or in other scenarios.

“These are not hypothetical conversations,” Dr. Angel said. “I’m having these conversations with patients now – temporary use, they travel for 3 months and come back, can they go from injectable to oral to injectable.”

For now, he said, the answer is, “We’ll figure it out.”

Meanwhile, there’s another big question when it comes to injectables, said Marta Vas ylyev, MD, from Lviv (Ukraine) Regional AIDS Center: When will they be available to the people who might benefit most from them – people in resource-limited settings, people who so far have struggled to remember to take their pills every day?

For now, Dr. Angel replied, injectables continue to be a treatment only for those who are already doing well while receiving HIV treatment: those with already suppressed viral load, who are good at taking daily pills, and who are being treated at well-resourced clinics.

“There are huge obstacles to overcome if this is ever to be available [in resource-limited settings], and way more obstacles than there are with any oral therapies,” he said. “There’s not been much discussion here about the necessity of cold-chain requirements of pharmacies either centrally or locally, [or] the requirements of additional nurses or health care staff to administer the medication. So you’re looking at a very resource-intensive therapy, which now is fairly restrictive [as to] who will have access to it.”

Dr. Angel reports serving on advisory boards for ViiV Healthcare and Gilead Sciences and has done contract research for ViiV Healthcare, Gilead, and Merck. Dr. Orkin has received research grants, fees as a consultant, travel sponsorship, and speaker fees from ViiV, Merck, and GlaxoSmithKline. Dr. Vasylyev reported no relevant financial relationships.  

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

One year into offering the first long-acting injectable HIV treatment to his patients, Jonathan Angel, MD, head of the division of infectious diseases at the University of Ottawa, reported that 15 of the 21 of patients who started on the regimen are still taking it, all with viral suppression. Those who weren’t cited a combination of inconvenience, injection site pain, and “injection fatigue.”

These are just a few things HIV providers are learning as they begin what Chloe Orkin, MD, professor of HIV medicine at Queen Mary University of London, called a paradigm shift to long-acting treatment, which may soon include not just shots but rings, implants, and microarray patches.

“It’s a paradigm shift, and we are at the very beginning of this paradigm shift,” said Dr. Orkin, commenting during the discussion session of the European AIDS Clinical Society 2021 annual meeting. “We’re having to change our model, and it’s challenging.”

In the United States, the Food and Drug Administration approved the first long-acting injectable, a combination of cabotegravir and rilpivirine (CAB/RIL; Cabenuva, ViiV Healthcare) in January 2021. But it has been approved in Canada since March 2020 and available at Dr. Angel’s clinic since November 2020. It’s also available in Canada as an every-other-month shot. Injected into the buttocks, the shot was found to be noninferior to standard daily oral treatment in many studies, including the ATLAS, the ATLAS-2M – which tested the every-other-month approach – and FLAIR trials.

Dr. Angel’s clinic was part of all three of those trials, so his clinic has had 5 years’ experience preparing for the change in workflow and the new approach the shots require.

Of the 21 people Dr. Angel has treated, 11 were white Canadians, nine were Black African, and one was Indigenous Canadian, with women making up a third of the participants. Median age was 51 years, and all patients had had undetectable viral loads before beginning the regimen. (Studies of the drug’s effectiveness in people who struggle to take daily pills are still ongoing.)

Most of those 21 patients had had undetectable viral loads for more than 5 years, but a few had been undetectable for only 6 months before beginning the shots. Their immune systems were also healthy, with a median CD4 count of 618 cells/mcL. As in the clinical trials, none of the participants had experienced antiretroviral treatment failure. Because public health insurers in Canada have yet to approve the shots, Dr. Angel’s patients receiving Cabenuva also have private health insurance. Up to 90% of people in Canada receive pharmaceutical coverage through public insurance; therefore, the shot is not yet widely available.

Twenty patients switched from integrase-inhibitor regimens, and one had been receiving a nonnucleoside reverse transcriptase inhibitor–based regimen before starting Cabenuva.

And although the drug has not been approved for shot initiation this way, two patients requested – and Dr. Angel agreed – to start them on the shots without first doing a month of daily pills to check for safety.

“This is my conclusion from these data: the oral lead-in period is not necessary,” Dr. Angel said in his presentation at the meeting. “It can provide some comfort to either a physician or a patient, but it does not seem to be medically necessary.”

That approach is not without data to back it up. Research presented at HIV Glasgow 2020 showed that people who switched from daily oral dolutegravir/abacavir/lamivudine straight to the injections did so without problems.

At last clinic visit, 15 of those 21 were still receiving the shots. None have experienced treatment failure, and all were still virally suppressed. Four participants left the trials and one more person opted to return to daily pills, citing some level of what Dr. Angel called “injection fatigue.”

“Just as we use the term ‘pill fatigue’ for patients who are tired of taking pills, patients do get tired of coming in monthly for their visits and injections,” he said. They find the trip to the clinic for the intramuscular injections “inconvenient,” he said.

Unlike in the United States, where Cabenuva is approved for only monthly injections, Health Canada has already approved the shot for every-other-month injections, which Dr. Angel said may reduce the odds of injection fatigue.

Dr. Angel’s presentation drew comments, questions, and excitement from the crowd. Annemarie Wensing, MD, assistant professor of medicine at University Medical Center Utrecht (the Netherlands), asked whether dispensing with the oral lead-in period could mean that these shots could be useful for people going on longer trips, people having surgeries where they can’t swallow pills, or in other scenarios.

“These are not hypothetical conversations,” Dr. Angel said. “I’m having these conversations with patients now – temporary use, they travel for 3 months and come back, can they go from injectable to oral to injectable.”

For now, he said, the answer is, “We’ll figure it out.”

Meanwhile, there’s another big question when it comes to injectables, said Marta Vas ylyev, MD, from Lviv (Ukraine) Regional AIDS Center: When will they be available to the people who might benefit most from them – people in resource-limited settings, people who so far have struggled to remember to take their pills every day?

For now, Dr. Angel replied, injectables continue to be a treatment only for those who are already doing well while receiving HIV treatment: those with already suppressed viral load, who are good at taking daily pills, and who are being treated at well-resourced clinics.

“There are huge obstacles to overcome if this is ever to be available [in resource-limited settings], and way more obstacles than there are with any oral therapies,” he said. “There’s not been much discussion here about the necessity of cold-chain requirements of pharmacies either centrally or locally, [or] the requirements of additional nurses or health care staff to administer the medication. So you’re looking at a very resource-intensive therapy, which now is fairly restrictive [as to] who will have access to it.”

Dr. Angel reports serving on advisory boards for ViiV Healthcare and Gilead Sciences and has done contract research for ViiV Healthcare, Gilead, and Merck. Dr. Orkin has received research grants, fees as a consultant, travel sponsorship, and speaker fees from ViiV, Merck, and GlaxoSmithKline. Dr. Vasylyev reported no relevant financial relationships.  

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

The more fast food restaurants a person lives near in the United States, the more likely they are to develop type 2 diabetes, new research indicates.  

The national study of more than 4 million U.S. veterans also found the opposite association with supermarkets in suburban and rural communities but not others.

“Neighborhood food environment was associated with type 2 diabetes risk among U.S. veterans in multiple community types, suggesting potential avenues for action to address the burden of type 2 diabetes,” say Rania Kanchi, MPH, of the department of population health, New York University Langone Health, and colleagues.

Restriction of fast food establishments could benefit all types of communities, while interventions to increase supermarket availability could help minimize diabetes risk in suburban and rural communities, they stress.

“These actions, combined with increasing awareness of the risk of type 2 diabetes and the importance of healthy diet intake, might be associated with a decrease in the burden of type 2 diabetes among adults in the U.S.,” the researchers add.

The data were published online Oct. 29 in JAMA Network Open.

“The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents,” commented Lorna Thorpe, PhD, MPH, professor in the department of population health at NYU Langone and senior author of the study in a press release.

In an accompanying editorial, Elham Hatef, MD, MPH, of the Center for Population Health IT at Johns Hopkins Bloomberg School of Public Health, Baltimore, calls the study “a great example of the capabilities of [health information technology] to provide a comprehensive assessment of a person’s health, which goes beyond just documenting clinical diseases and medical interventions.”
 

Research has large geographic breadth

The study is notable for its large geographic breadth, say the researchers.

“Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas,” Ms. Kanchi said in the press statement.

“Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not,” Ms. Kanchi continued.

The research included data for 4,100,650 individuals from the Veterans Affairs electronic health records (EHRs) who didn’t have type 2 diabetes at baseline, between 2008 and 2016. After a median follow-up of 5.5 person-years, 13.2% developed type 2 diabetes. Cumulative incidence was greater among those who were older, those who were non-Hispanic Black compared with other races, and those with disabilities and lower incomes.

The proportion of adults with type 2 diabetes was highest among those living in high-density urban communities (14.3%), followed by low-density urban (13.1%), rural (13.2%), and suburban (12.6%) communities.

Overall, a 10% increase in the number of fast food restaurants compared with other food establishments in a given neighborhood was associated with a 1% increased risk for incident type 2 diabetes in high-density urban, low-density urban, and rural communities and a 2% increased risk in suburban communities.

In contrast, a 10% increase in supermarket density compared with other food stores was associated with a lower risk for type 2 diabetes in suburban and rural communities, but the association wasn’t significant elsewhere.

“Taken together, our findings suggest that policies specific to fast food restaurants, such as [those] ... restricting the siting of fast food restaurants and healthy beverage default laws, may be effective in reducing type 2 diabetes risk in all community types,” say the authors.

“In urban areas where population and retail density are growing, it will be even more important to focus on these policies,” they emphasize.
 

Great example of capabilities of health information technology

In the editorial, Dr. Hatef notes that methodological advances, such as natural language processing and machine learning, have enabled health systems to use real-world data such as the free-text notes in the EHR to identify patient-level risk factors for diseases or disease complications.

Such methods could be further used to “evaluate the associations between social needs and place-based [social determinants of health] and type 2 diabetes incidence and management,” Dr. Hatef adds.

And linkage of data from the EHR to such community-level data “would help to comprehensively assess and identify patients likely to experience type 2 diabetes and its complications as a result of their risk factors or characteristics of the neighborhoods where they reside.”

“This approach could foster collaborations between the health systems and at-risk communities they serve and help to reallocate health system resources to those in most need in the community to reduce the burden of type 2 diabetes and other chronic conditions among racial minority groups and socioeconomically disadvantaged patients and to advance population health.”

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the Commonwealth Universal Research Enhancement program funded by the Pennsylvania Department of Health, the Urban Health Collaborative at Drexel University, and the Built Environment and Health Research Group at Columbia University. Ms. Kanchi and Dr. Hatef have reported no relevant financial relationships.

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

The more fast food restaurants a person lives near in the United States, the more likely they are to develop type 2 diabetes, new research indicates.  

The national study of more than 4 million U.S. veterans also found the opposite association with supermarkets in suburban and rural communities but not others.

“Neighborhood food environment was associated with type 2 diabetes risk among U.S. veterans in multiple community types, suggesting potential avenues for action to address the burden of type 2 diabetes,” say Rania Kanchi, MPH, of the department of population health, New York University Langone Health, and colleagues.

Restriction of fast food establishments could benefit all types of communities, while interventions to increase supermarket availability could help minimize diabetes risk in suburban and rural communities, they stress.

“These actions, combined with increasing awareness of the risk of type 2 diabetes and the importance of healthy diet intake, might be associated with a decrease in the burden of type 2 diabetes among adults in the U.S.,” the researchers add.

The data were published online Oct. 29 in JAMA Network Open.

“The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents,” commented Lorna Thorpe, PhD, MPH, professor in the department of population health at NYU Langone and senior author of the study in a press release.

In an accompanying editorial, Elham Hatef, MD, MPH, of the Center for Population Health IT at Johns Hopkins Bloomberg School of Public Health, Baltimore, calls the study “a great example of the capabilities of [health information technology] to provide a comprehensive assessment of a person’s health, which goes beyond just documenting clinical diseases and medical interventions.”
 

Research has large geographic breadth

The study is notable for its large geographic breadth, say the researchers.

“Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas,” Ms. Kanchi said in the press statement.

“Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not,” Ms. Kanchi continued.

The research included data for 4,100,650 individuals from the Veterans Affairs electronic health records (EHRs) who didn’t have type 2 diabetes at baseline, between 2008 and 2016. After a median follow-up of 5.5 person-years, 13.2% developed type 2 diabetes. Cumulative incidence was greater among those who were older, those who were non-Hispanic Black compared with other races, and those with disabilities and lower incomes.

The proportion of adults with type 2 diabetes was highest among those living in high-density urban communities (14.3%), followed by low-density urban (13.1%), rural (13.2%), and suburban (12.6%) communities.

Overall, a 10% increase in the number of fast food restaurants compared with other food establishments in a given neighborhood was associated with a 1% increased risk for incident type 2 diabetes in high-density urban, low-density urban, and rural communities and a 2% increased risk in suburban communities.

In contrast, a 10% increase in supermarket density compared with other food stores was associated with a lower risk for type 2 diabetes in suburban and rural communities, but the association wasn’t significant elsewhere.

“Taken together, our findings suggest that policies specific to fast food restaurants, such as [those] ... restricting the siting of fast food restaurants and healthy beverage default laws, may be effective in reducing type 2 diabetes risk in all community types,” say the authors.

“In urban areas where population and retail density are growing, it will be even more important to focus on these policies,” they emphasize.
 

Great example of capabilities of health information technology

In the editorial, Dr. Hatef notes that methodological advances, such as natural language processing and machine learning, have enabled health systems to use real-world data such as the free-text notes in the EHR to identify patient-level risk factors for diseases or disease complications.

Such methods could be further used to “evaluate the associations between social needs and place-based [social determinants of health] and type 2 diabetes incidence and management,” Dr. Hatef adds.

And linkage of data from the EHR to such community-level data “would help to comprehensively assess and identify patients likely to experience type 2 diabetes and its complications as a result of their risk factors or characteristics of the neighborhoods where they reside.”

“This approach could foster collaborations between the health systems and at-risk communities they serve and help to reallocate health system resources to those in most need in the community to reduce the burden of type 2 diabetes and other chronic conditions among racial minority groups and socioeconomically disadvantaged patients and to advance population health.”

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the Commonwealth Universal Research Enhancement program funded by the Pennsylvania Department of Health, the Urban Health Collaborative at Drexel University, and the Built Environment and Health Research Group at Columbia University. Ms. Kanchi and Dr. Hatef have reported no relevant financial relationships.

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

The more fast food restaurants a person lives near in the United States, the more likely they are to develop type 2 diabetes, new research indicates.  

The national study of more than 4 million U.S. veterans also found the opposite association with supermarkets in suburban and rural communities but not others.

“Neighborhood food environment was associated with type 2 diabetes risk among U.S. veterans in multiple community types, suggesting potential avenues for action to address the burden of type 2 diabetes,” say Rania Kanchi, MPH, of the department of population health, New York University Langone Health, and colleagues.

Restriction of fast food establishments could benefit all types of communities, while interventions to increase supermarket availability could help minimize diabetes risk in suburban and rural communities, they stress.

“These actions, combined with increasing awareness of the risk of type 2 diabetes and the importance of healthy diet intake, might be associated with a decrease in the burden of type 2 diabetes among adults in the U.S.,” the researchers add.

The data were published online Oct. 29 in JAMA Network Open.

“The more we learn about the relationship between the food environment and chronic diseases like type 2 diabetes, the more policymakers can act by improving the mix of healthy food options sold in restaurants and food outlets, or by creating better zoning laws that promote optimal food options for residents,” commented Lorna Thorpe, PhD, MPH, professor in the department of population health at NYU Langone and senior author of the study in a press release.

In an accompanying editorial, Elham Hatef, MD, MPH, of the Center for Population Health IT at Johns Hopkins Bloomberg School of Public Health, Baltimore, calls the study “a great example of the capabilities of [health information technology] to provide a comprehensive assessment of a person’s health, which goes beyond just documenting clinical diseases and medical interventions.”
 

Research has large geographic breadth

The study is notable for its large geographic breadth, say the researchers.

“Most studies that examine the built food environment and its relationship to chronic diseases have been much smaller or conducted in localized areas,” Ms. Kanchi said in the press statement.

“Our study design is national in scope and allowed us to identify the types of communities that people are living in, characterize their food environment, and observe what happens to them over time. The size of our cohort allows for geographic generalizability in a way that other studies do not,” Ms. Kanchi continued.

The research included data for 4,100,650 individuals from the Veterans Affairs electronic health records (EHRs) who didn’t have type 2 diabetes at baseline, between 2008 and 2016. After a median follow-up of 5.5 person-years, 13.2% developed type 2 diabetes. Cumulative incidence was greater among those who were older, those who were non-Hispanic Black compared with other races, and those with disabilities and lower incomes.

The proportion of adults with type 2 diabetes was highest among those living in high-density urban communities (14.3%), followed by low-density urban (13.1%), rural (13.2%), and suburban (12.6%) communities.

Overall, a 10% increase in the number of fast food restaurants compared with other food establishments in a given neighborhood was associated with a 1% increased risk for incident type 2 diabetes in high-density urban, low-density urban, and rural communities and a 2% increased risk in suburban communities.

In contrast, a 10% increase in supermarket density compared with other food stores was associated with a lower risk for type 2 diabetes in suburban and rural communities, but the association wasn’t significant elsewhere.

“Taken together, our findings suggest that policies specific to fast food restaurants, such as [those] ... restricting the siting of fast food restaurants and healthy beverage default laws, may be effective in reducing type 2 diabetes risk in all community types,” say the authors.

“In urban areas where population and retail density are growing, it will be even more important to focus on these policies,” they emphasize.
 

Great example of capabilities of health information technology

In the editorial, Dr. Hatef notes that methodological advances, such as natural language processing and machine learning, have enabled health systems to use real-world data such as the free-text notes in the EHR to identify patient-level risk factors for diseases or disease complications.

Such methods could be further used to “evaluate the associations between social needs and place-based [social determinants of health] and type 2 diabetes incidence and management,” Dr. Hatef adds.

And linkage of data from the EHR to such community-level data “would help to comprehensively assess and identify patients likely to experience type 2 diabetes and its complications as a result of their risk factors or characteristics of the neighborhoods where they reside.”

“This approach could foster collaborations between the health systems and at-risk communities they serve and help to reallocate health system resources to those in most need in the community to reduce the burden of type 2 diabetes and other chronic conditions among racial minority groups and socioeconomically disadvantaged patients and to advance population health.”

The study was supported by the Centers for Disease Control and Prevention, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Aging, the Commonwealth Universal Research Enhancement program funded by the Pennsylvania Department of Health, the Urban Health Collaborative at Drexel University, and the Built Environment and Health Research Group at Columbia University. Ms. Kanchi and Dr. Hatef have reported no relevant financial relationships.

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

Women who take a wide variety of disease-modifying therapies (DMTs) for multiple sclerosis (MS) – not just those on a few types – may be especially susceptible to hair loss via alopecia, a new study finds.

From 2009 to 2019, the Food and Drug Administration received 7,978 reports of new-onset alopecia in patients taking DMTs, particularly teriflunomide (3,255, 40.8%; 90% female), dimethyl fumarate (1,641, 20.6%; 89% female), natalizumab (955, 12.0%; 92% female), and fingolimod (776, 9.7% of the total reports; 93% female), several researchers reported at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). Of these, only teriflunomide had previously been linked to alopecia, study coauthor Ahmed Obeidat, MD, PhD, a neurologist at the Medical College of Wisconsin, Milwaukee, said in an interview.

“Our finding of frequent reports of alopecia on DMTs studied calls for further investigation into the subject,” Dr. Obeidat said. “Alopecia can cause deep personal impacts and can be a source of significant psychological concern for some patients.”

According to Dr. Obeidat, alopecia has been linked to the only a few DMTs – cladribine and the interferons – in addition to teriflunomide. “To our surprise, we received anecdotal reports of hair thinning from several of our MS patients treated with various other [DMTs]. Upon further investigation, we could not find substantial literature to explain this phenomenon which led us to conduct our investigation.”

Dr. Obeidat and colleagues identified DMT-related alopecia cases (18.3%) among 43,655 reports in the skin and subcutaneous tissue disorder category in the FDA Adverse Event Reporting System. Other DMTs with more than 1 case report were interferon beta-1a (635, 8.0%; 92% female), glatiramer acetate (332, 4.2%; 87% female), ocrelizumab (142, 1.8%; 94% female), interferon beta-1b (126, 1.6%; 95% female), alemtuzumab (86, 1.1%; 88% female), cladribine (17, 0.2%; 65% female), and rituximab (10, 0.1%; 90% female).

The average age for the case reports varied from 42 to 51 years for most of the drugs except alemtuzumab (mean age, 40 years) and cladribine (average age, 38 years), which had low numbers of cases.

Siponimod (three cases) and ozanimod (no cases) were not included in the age and gender analyses.

Why do so many women seem to be affected, well beyond their percentage of MS cases overall? The answer is unclear, said medical student Mokshal H. Porwal, the study’s lead author. “There could be a biological explanation,” Mr. Porwal said, “or women may report cases more often: “Earlier studies suggested that alopecia may affect women more adversely in terms of body image as well as overall psychological well-being, compared to males.”

The researchers also noted that patients – not medical professionals – provided most of the case reports in the FDA database. “We believe this indicates that alopecia is a patient-centered concern that may have a larger impact on their lives than what the health care teams may perceive,” Mr. Porwal said. “Oftentimes, we as health care providers, look for the more acute and apparent adverse events, which can overshadow issues such as hair thinning/alopecia that could have even greater psychological impacts on our patients.”

Dr. Obeidat said there are still multiple mysteries about DMT and alopecia risk: the true incidence of cases per DMT or DMT class, the mechanism(s) behind a link, the permanent or transient nature of the alopecia cases, and the risk factors in individual patients.

Going forward, he said, “we advise clinicians to discuss hair thinning or alopecia as a possible side effect that has been reported in association with all DMTs in the real-world, postmarketing era.”

No study funding was reported. Dr. Obeidat reported various disclosures; the other authors reported no disclosures.

Women who take a wide variety of disease-modifying therapies (DMTs) for multiple sclerosis (MS) – not just those on a few types – may be especially susceptible to hair loss via alopecia, a new study finds.

From 2009 to 2019, the Food and Drug Administration received 7,978 reports of new-onset alopecia in patients taking DMTs, particularly teriflunomide (3,255, 40.8%; 90% female), dimethyl fumarate (1,641, 20.6%; 89% female), natalizumab (955, 12.0%; 92% female), and fingolimod (776, 9.7% of the total reports; 93% female), several researchers reported at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). Of these, only teriflunomide had previously been linked to alopecia, study coauthor Ahmed Obeidat, MD, PhD, a neurologist at the Medical College of Wisconsin, Milwaukee, said in an interview.

“Our finding of frequent reports of alopecia on DMTs studied calls for further investigation into the subject,” Dr. Obeidat said. “Alopecia can cause deep personal impacts and can be a source of significant psychological concern for some patients.”

According to Dr. Obeidat, alopecia has been linked to the only a few DMTs – cladribine and the interferons – in addition to teriflunomide. “To our surprise, we received anecdotal reports of hair thinning from several of our MS patients treated with various other [DMTs]. Upon further investigation, we could not find substantial literature to explain this phenomenon which led us to conduct our investigation.”

Dr. Obeidat and colleagues identified DMT-related alopecia cases (18.3%) among 43,655 reports in the skin and subcutaneous tissue disorder category in the FDA Adverse Event Reporting System. Other DMTs with more than 1 case report were interferon beta-1a (635, 8.0%; 92% female), glatiramer acetate (332, 4.2%; 87% female), ocrelizumab (142, 1.8%; 94% female), interferon beta-1b (126, 1.6%; 95% female), alemtuzumab (86, 1.1%; 88% female), cladribine (17, 0.2%; 65% female), and rituximab (10, 0.1%; 90% female).

The average age for the case reports varied from 42 to 51 years for most of the drugs except alemtuzumab (mean age, 40 years) and cladribine (average age, 38 years), which had low numbers of cases.

Siponimod (three cases) and ozanimod (no cases) were not included in the age and gender analyses.

Why do so many women seem to be affected, well beyond their percentage of MS cases overall? The answer is unclear, said medical student Mokshal H. Porwal, the study’s lead author. “There could be a biological explanation,” Mr. Porwal said, “or women may report cases more often: “Earlier studies suggested that alopecia may affect women more adversely in terms of body image as well as overall psychological well-being, compared to males.”

The researchers also noted that patients – not medical professionals – provided most of the case reports in the FDA database. “We believe this indicates that alopecia is a patient-centered concern that may have a larger impact on their lives than what the health care teams may perceive,” Mr. Porwal said. “Oftentimes, we as health care providers, look for the more acute and apparent adverse events, which can overshadow issues such as hair thinning/alopecia that could have even greater psychological impacts on our patients.”

Dr. Obeidat said there are still multiple mysteries about DMT and alopecia risk: the true incidence of cases per DMT or DMT class, the mechanism(s) behind a link, the permanent or transient nature of the alopecia cases, and the risk factors in individual patients.

Going forward, he said, “we advise clinicians to discuss hair thinning or alopecia as a possible side effect that has been reported in association with all DMTs in the real-world, postmarketing era.”

No study funding was reported. Dr. Obeidat reported various disclosures; the other authors reported no disclosures.

Women who take a wide variety of disease-modifying therapies (DMTs) for multiple sclerosis (MS) – not just those on a few types – may be especially susceptible to hair loss via alopecia, a new study finds.

From 2009 to 2019, the Food and Drug Administration received 7,978 reports of new-onset alopecia in patients taking DMTs, particularly teriflunomide (3,255, 40.8%; 90% female), dimethyl fumarate (1,641, 20.6%; 89% female), natalizumab (955, 12.0%; 92% female), and fingolimod (776, 9.7% of the total reports; 93% female), several researchers reported at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). Of these, only teriflunomide had previously been linked to alopecia, study coauthor Ahmed Obeidat, MD, PhD, a neurologist at the Medical College of Wisconsin, Milwaukee, said in an interview.

“Our finding of frequent reports of alopecia on DMTs studied calls for further investigation into the subject,” Dr. Obeidat said. “Alopecia can cause deep personal impacts and can be a source of significant psychological concern for some patients.”

According to Dr. Obeidat, alopecia has been linked to the only a few DMTs – cladribine and the interferons – in addition to teriflunomide. “To our surprise, we received anecdotal reports of hair thinning from several of our MS patients treated with various other [DMTs]. Upon further investigation, we could not find substantial literature to explain this phenomenon which led us to conduct our investigation.”

Dr. Obeidat and colleagues identified DMT-related alopecia cases (18.3%) among 43,655 reports in the skin and subcutaneous tissue disorder category in the FDA Adverse Event Reporting System. Other DMTs with more than 1 case report were interferon beta-1a (635, 8.0%; 92% female), glatiramer acetate (332, 4.2%; 87% female), ocrelizumab (142, 1.8%; 94% female), interferon beta-1b (126, 1.6%; 95% female), alemtuzumab (86, 1.1%; 88% female), cladribine (17, 0.2%; 65% female), and rituximab (10, 0.1%; 90% female).

The average age for the case reports varied from 42 to 51 years for most of the drugs except alemtuzumab (mean age, 40 years) and cladribine (average age, 38 years), which had low numbers of cases.

Siponimod (three cases) and ozanimod (no cases) were not included in the age and gender analyses.

Why do so many women seem to be affected, well beyond their percentage of MS cases overall? The answer is unclear, said medical student Mokshal H. Porwal, the study’s lead author. “There could be a biological explanation,” Mr. Porwal said, “or women may report cases more often: “Earlier studies suggested that alopecia may affect women more adversely in terms of body image as well as overall psychological well-being, compared to males.”

The researchers also noted that patients – not medical professionals – provided most of the case reports in the FDA database. “We believe this indicates that alopecia is a patient-centered concern that may have a larger impact on their lives than what the health care teams may perceive,” Mr. Porwal said. “Oftentimes, we as health care providers, look for the more acute and apparent adverse events, which can overshadow issues such as hair thinning/alopecia that could have even greater psychological impacts on our patients.”

Dr. Obeidat said there are still multiple mysteries about DMT and alopecia risk: the true incidence of cases per DMT or DMT class, the mechanism(s) behind a link, the permanent or transient nature of the alopecia cases, and the risk factors in individual patients.

Going forward, he said, “we advise clinicians to discuss hair thinning or alopecia as a possible side effect that has been reported in association with all DMTs in the real-world, postmarketing era.”

No study funding was reported. Dr. Obeidat reported various disclosures; the other authors reported no disclosures.

It’s undeniable that great strides have been made in advancing the science of multiple sclerosis (MS) over the past 20 years. Continued pursuit of research and discovery has revolutionized the understanding, diagnosis, and treatment of this debilitating condition that causes symptoms that may impact nearly every part of the body and mind. Despite these advancements, there is still more work to be done.

As the search for a cure continues, it’s imperative to ask the big questions: How does MS develop and progress? How can we reduce health disparities in care and treatment? How can we improve existing treatments and expedite the discovery of new ones? To continue making progress, we must stretch the boundaries of scientific understanding until we have answers and solutions to these and other important questions.

We know that MS is a leading cause of non-traumatic disability for young people.^1,2 Yet, one of the biggest challenges for neurologists is that every person’s experience with MS is unique, making it difficult to predict what symptoms will manifest, how disruptive the symptoms and relapses will be and how a person will respond to treatment.

Twenty years ago, it was widely thought that MS was mainly driven by T cells, but in the late 1990’s, a team of researchers made a groundbreaking discovery: B cells also played a key role in MS. This discovery redefined how the scientific community thought about the underlying biology of MS and the central role B cells can play. 

It was this bold thinking that led researchers at the University of California, San Francisco (UCSF) and scientists at Genentech, a member of the Roche Group, to explore whether a medication that depleted B cells would have an impact on MS. This collaboration, in turn, inspired the clinical research behind Ocrevus^® (ocrelizumab), the first and only treatment approved by the FDA for both relapsing MS (RMS) and primary progressive MS (PPMS). MS is a progressive disease from the start. An important goal of treating MS is to reduce disease progression as soon as possible to slow how quickly a person’s disability changes and prevent the long-term consequences of disease progression.³ Ocrevus is administered via infusion twice yearly, with the initial dose split into two separate infusions and given two weeks apart. As with any therapy, this treatment has side effects, which can be found in the full Prescribing Information and Medication Guide. Ocrevus is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reactions to Ocrevus. The warnings and precautions for Ocrevus are infusion reactions, and infections, which include respiratory tract infections, herpes, progressive multifocal leukoencephalopathy (PML), and hepatitis B virus (HBV) reactivation. Additional warnings are possible increased risk of immunosuppressant effects with other immunosuppressants, reduction in immunoglobulins, and malignancies.

Ensuring a Continuum of Care 
Another significant challenge facing the MS community is ensuring ongoing support and care for people living with the condition, especially throughout the COVID-19 pandemic. “We know that seeking early and appropriate care for MS is critical to slowing disability progression and achieving successful patient outcomes,” said Dr. Ashish Pradhan, Executive Director of Neuroimmunology at Genentech. “The pandemic has created additional barriers to early diagnosis and treatment, but we are committed to continuing to do everything we can to support patients and physicians at this stressful time.” Dr. Pradhan also observed that FDA's approval of a shorter infusion time for Ocrevus in December 2020 could potentially contribute to reducing some of the burden on the healthcare system in the long-term.

Being able to connect with others in the MS community is a vital part of navigating the uncertainties of living with the condition. This past April, to shine a light on the diverse MS community, Genentech hosted an #MSVisibility Virtual Concert that gathered people from across the world with different backgrounds and MS experiences and encouraged people living with MS to continue seeking appropriate support and care during the pandemic.

Continued support of the MS community through advocacy partnerships and grants over the years has played a sustained role in Genentech’s efforts to ensure people with MS receive necessary medical care and treatment. For example, Genentech partnered with an MS advocacy organization to fund a program that helps people get to and from their medical appointments. In addition, for more than 30 years, Genentech has helped more than two million people get the medicine they need through patient assistance programs like Genentech Access Solutions and the Genentech Patient Foundation.

Advancing Inclusive Research in MS 
MS has been shown to impact individuals and specific populations in markedly different ways. Those who identify as Black or of African descent and Hispanic/Latinos for example can experience more severe symptoms and faster disease progression than their Caucasian counterparts.^4,5 Unfortunately, it’s not clear exactly why, largely because of their vast underrepresentation in clinical trials (less than 5% and 1%, respectively).⁶ While there are multiple explanations for these disparities, around one-in-three minority patients don’t participate in clinical trials due to lack of trust and 52% feel that the healthcare system is not only flawed, but is actually working against them.⁷

“Increased diversity in research is paramount to ensuring that the healthcare system is serving every person living with MS and ultimately reducing health inequities while providing more tailored treatment options,” commented Dr. Pradhan. “To advance the care of undertreated and underserved people with MS, we are creating and supporting programs, grants and other initiatives focused on people of color and inclusive and minority research to better understand how MS presents itself and develops in different patient populations. We want to make sure that all generations of people living with MS are equally represented in clinical research and have access to the treatments that will work best for them.”

Refining Existing Approaches and Leading Treatment Innovation
For decades, Genentech and Roche have been conducting neuroscience research and clinical trials to make forward progress in understanding and treating a variety of neurological conditions, including MS. While the treatment landscape for MS has evolved significantly over the past two decades, continued investment in research and development is critical. Continuing to review and refine existing treatment approaches may improve patient outcomes and discovering new treatment approaches may play an important role in advancing the treatment paradigm.

Dr. Pradhan added, “as the scientific community continues to think boldly, and re-imagine treatment and care for MS, we hope to continue to improve our understanding of the condition for all people with the disease, and advance treatment options. Pushing boundaries means refusing to stop until everyone living with MS can be treated effectively and a cure is found. This sentiment reminds me of a Ralph Waldo Emerson quote, ‘Don’t follow where the path may lead. Go instead where there is no path and leave a trail.’ That’s what we are trying to do at Genentech.”

To learn more, please visit Ocrevus.com.

Indications and Important Safety Information
OCREVUS is indicated for the treatment of:

• Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
• Primary progressive MS, in adults. 

Contraindications
OCREVUS is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reaction to OCREVUS.

Warnings and Precautions

Infusion Reactions  

OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis. In multiple sclerosis (MS) clinical trials, the incidence of infusion reactions in OCREVUS-treated patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to each infusion] was 34-40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of OCREVUS-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization.  

Observe patients treated with OCREVUS for infusion reactions during the infusion and for at least one hour after completion of the infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered. For life-threatening infusion reactions, immediately and permanently stop OCREVUS and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of OCREVUS-treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS increased the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. OCREVUS was not associated with an increased risk of serious infections in MS patients. Delay OCREVUS administration in patients with an active infection until the infection is resolved.

Respiratory Tract Infections

A higher proportion of OCREVUS-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 43% of patients on placebo and 10% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.

Herpes

In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in OCREVUS-treated patients than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the OCREVUS-treated patients than in the patients on placebo (2.7% vs 0.8%).

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving OCREVUS. Serious herpes virus infections may occur at any time during treatment with OCREVUS. Some cases were life-threatening. 

If serious herpes infections occur, OCREVUS should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered.

Progressive Multifocal Leukoencephalopathy (PML)

PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no cases of PML were identified in OCREVUS clinical trials, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). At the first sign or symptom suggestive of PML, withhold OCREVUS and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes (per USPI).

Hepatitis B Virus (HBV) Reactivation

Hepatitis B reactivation has been reported in MS patients treated with OCREVUS in the postmarketing setting. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with OCREVUS. Do not administer OCREVUS to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment.

Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants

When initiating OCREVUS after an immunosuppressive therapy or initiating an immunosuppressive therapy after OCREVUS, consider the potential for increased immunosuppressive effect. OCREVUS has not been studied in combination with other MS therapies.

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines. OCREVUS may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following OCREVUS therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with OCREVUS treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during OCREVUS treatment and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing OCREVUS therapy in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Malignancies  

An increased risk of malignancy with OCREVUS may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in OCREVUS-treated patients. Breast cancer occurred in 6 of 781 females treated with OCREVUS and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines.

Use in Specific Populations

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to OCREVUS during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-872-4370 or visiting www.ocrevuspregnancyregistry.com.

There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to OCREVUS. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier. 

Lactation 

There are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OCREVUS and any potential adverse effects on the breastfed infant from OCREVUS or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving OCREVUS and for 6 months after the last infusion of OCREVUS.

Most Common Adverse Reactions

RMS: The most common adverse reactions in RMS trials (incidence ≥10% and >REBIF) were upper respiratory tract infections (40%) and infusion reactions (34%).
 

PPMS: The most common adverse reactions in PPMS trials (incidence ≥10% and >placebo) were upper respiratory tract infections (49%), infusion reactions (40%), skin infections (14%), and lower respiratory tract infections (10%).

For additional safety information, please see the full Prescribing Information and Medication Guide.

¹ Murray TJ. (2006). Diagnosis and Treatment of Multiple Sclerosis. BMJ, 322 (7540):525-527.
² Tullman M. (2013). Overview of the Epidemiology, Diagnosis, and Disease Progression Associated With Multiple Sclerosis. The American Journal of Managed Care. 19 (2): S15-S20.
³ National Institutes of Health-National Institute of Neurological Disorders and Stroke. (2015). Multiple Sclerosis: Hope Through Research. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Multiple-Sclerosis-Hope-Through-Research.
⁴ National MS Society. "Who Gets MS? - African Americans." Retrieved November 2020. nationalmssociety.org/What-is-MS/Who-Gets-MS/African-American-Resources.
⁵ Langer-Gould A, et al. Neurology. 2013;80:1734-1739; 2. Wallin MT, et al. Brain. 2012;135:1778-1785.
⁶ U.S. Food and Drug Administration. “Clinical Trials Shed Light on Minority Health.” U.S. Food and Drug Administration Website. https://wayback.archive-it.org/7993/20180908114418/https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm349063.htm. Published 2018.
⁷ Genentech. “A New Perspective on Health Inequity.” https://www.gene.com/stories/a-new-perspective-on-health-inequity.

It’s undeniable that great strides have been made in advancing the science of multiple sclerosis (MS) over the past 20 years. Continued pursuit of research and discovery has revolutionized the understanding, diagnosis, and treatment of this debilitating condition that causes symptoms that may impact nearly every part of the body and mind. Despite these advancements, there is still more work to be done.

As the search for a cure continues, it’s imperative to ask the big questions: How does MS develop and progress? How can we reduce health disparities in care and treatment? How can we improve existing treatments and expedite the discovery of new ones? To continue making progress, we must stretch the boundaries of scientific understanding until we have answers and solutions to these and other important questions.

We know that MS is a leading cause of non-traumatic disability for young people.^1,2 Yet, one of the biggest challenges for neurologists is that every person’s experience with MS is unique, making it difficult to predict what symptoms will manifest, how disruptive the symptoms and relapses will be and how a person will respond to treatment.

Twenty years ago, it was widely thought that MS was mainly driven by T cells, but in the late 1990’s, a team of researchers made a groundbreaking discovery: B cells also played a key role in MS. This discovery redefined how the scientific community thought about the underlying biology of MS and the central role B cells can play. 

It was this bold thinking that led researchers at the University of California, San Francisco (UCSF) and scientists at Genentech, a member of the Roche Group, to explore whether a medication that depleted B cells would have an impact on MS. This collaboration, in turn, inspired the clinical research behind Ocrevus^® (ocrelizumab), the first and only treatment approved by the FDA for both relapsing MS (RMS) and primary progressive MS (PPMS). MS is a progressive disease from the start. An important goal of treating MS is to reduce disease progression as soon as possible to slow how quickly a person’s disability changes and prevent the long-term consequences of disease progression.³ Ocrevus is administered via infusion twice yearly, with the initial dose split into two separate infusions and given two weeks apart. As with any therapy, this treatment has side effects, which can be found in the full Prescribing Information and Medication Guide. Ocrevus is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reactions to Ocrevus. The warnings and precautions for Ocrevus are infusion reactions, and infections, which include respiratory tract infections, herpes, progressive multifocal leukoencephalopathy (PML), and hepatitis B virus (HBV) reactivation. Additional warnings are possible increased risk of immunosuppressant effects with other immunosuppressants, reduction in immunoglobulins, and malignancies.

Ensuring a Continuum of Care 
Another significant challenge facing the MS community is ensuring ongoing support and care for people living with the condition, especially throughout the COVID-19 pandemic. “We know that seeking early and appropriate care for MS is critical to slowing disability progression and achieving successful patient outcomes,” said Dr. Ashish Pradhan, Executive Director of Neuroimmunology at Genentech. “The pandemic has created additional barriers to early diagnosis and treatment, but we are committed to continuing to do everything we can to support patients and physicians at this stressful time.” Dr. Pradhan also observed that FDA's approval of a shorter infusion time for Ocrevus in December 2020 could potentially contribute to reducing some of the burden on the healthcare system in the long-term.

Being able to connect with others in the MS community is a vital part of navigating the uncertainties of living with the condition. This past April, to shine a light on the diverse MS community, Genentech hosted an #MSVisibility Virtual Concert that gathered people from across the world with different backgrounds and MS experiences and encouraged people living with MS to continue seeking appropriate support and care during the pandemic.

Continued support of the MS community through advocacy partnerships and grants over the years has played a sustained role in Genentech’s efforts to ensure people with MS receive necessary medical care and treatment. For example, Genentech partnered with an MS advocacy organization to fund a program that helps people get to and from their medical appointments. In addition, for more than 30 years, Genentech has helped more than two million people get the medicine they need through patient assistance programs like Genentech Access Solutions and the Genentech Patient Foundation.

Advancing Inclusive Research in MS 
MS has been shown to impact individuals and specific populations in markedly different ways. Those who identify as Black or of African descent and Hispanic/Latinos for example can experience more severe symptoms and faster disease progression than their Caucasian counterparts.^4,5 Unfortunately, it’s not clear exactly why, largely because of their vast underrepresentation in clinical trials (less than 5% and 1%, respectively).⁶ While there are multiple explanations for these disparities, around one-in-three minority patients don’t participate in clinical trials due to lack of trust and 52% feel that the healthcare system is not only flawed, but is actually working against them.⁷

“Increased diversity in research is paramount to ensuring that the healthcare system is serving every person living with MS and ultimately reducing health inequities while providing more tailored treatment options,” commented Dr. Pradhan. “To advance the care of undertreated and underserved people with MS, we are creating and supporting programs, grants and other initiatives focused on people of color and inclusive and minority research to better understand how MS presents itself and develops in different patient populations. We want to make sure that all generations of people living with MS are equally represented in clinical research and have access to the treatments that will work best for them.”

Refining Existing Approaches and Leading Treatment Innovation
For decades, Genentech and Roche have been conducting neuroscience research and clinical trials to make forward progress in understanding and treating a variety of neurological conditions, including MS. While the treatment landscape for MS has evolved significantly over the past two decades, continued investment in research and development is critical. Continuing to review and refine existing treatment approaches may improve patient outcomes and discovering new treatment approaches may play an important role in advancing the treatment paradigm.

Dr. Pradhan added, “as the scientific community continues to think boldly, and re-imagine treatment and care for MS, we hope to continue to improve our understanding of the condition for all people with the disease, and advance treatment options. Pushing boundaries means refusing to stop until everyone living with MS can be treated effectively and a cure is found. This sentiment reminds me of a Ralph Waldo Emerson quote, ‘Don’t follow where the path may lead. Go instead where there is no path and leave a trail.’ That’s what we are trying to do at Genentech.”

To learn more, please visit Ocrevus.com.

Indications and Important Safety Information
OCREVUS is indicated for the treatment of:

• Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
• Primary progressive MS, in adults. 

Contraindications
OCREVUS is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reaction to OCREVUS.

Warnings and Precautions

Infusion Reactions  

OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis. In multiple sclerosis (MS) clinical trials, the incidence of infusion reactions in OCREVUS-treated patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to each infusion] was 34-40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of OCREVUS-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization.  

Observe patients treated with OCREVUS for infusion reactions during the infusion and for at least one hour after completion of the infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered. For life-threatening infusion reactions, immediately and permanently stop OCREVUS and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of OCREVUS-treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS increased the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. OCREVUS was not associated with an increased risk of serious infections in MS patients. Delay OCREVUS administration in patients with an active infection until the infection is resolved.

Respiratory Tract Infections

A higher proportion of OCREVUS-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 43% of patients on placebo and 10% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.

Herpes

In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in OCREVUS-treated patients than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the OCREVUS-treated patients than in the patients on placebo (2.7% vs 0.8%).

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving OCREVUS. Serious herpes virus infections may occur at any time during treatment with OCREVUS. Some cases were life-threatening. 

If serious herpes infections occur, OCREVUS should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered.

Progressive Multifocal Leukoencephalopathy (PML)

PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no cases of PML were identified in OCREVUS clinical trials, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). At the first sign or symptom suggestive of PML, withhold OCREVUS and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes (per USPI).

Hepatitis B Virus (HBV) Reactivation

Hepatitis B reactivation has been reported in MS patients treated with OCREVUS in the postmarketing setting. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with OCREVUS. Do not administer OCREVUS to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment.

Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants

When initiating OCREVUS after an immunosuppressive therapy or initiating an immunosuppressive therapy after OCREVUS, consider the potential for increased immunosuppressive effect. OCREVUS has not been studied in combination with other MS therapies.

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines. OCREVUS may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following OCREVUS therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with OCREVUS treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during OCREVUS treatment and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing OCREVUS therapy in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Malignancies  

An increased risk of malignancy with OCREVUS may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in OCREVUS-treated patients. Breast cancer occurred in 6 of 781 females treated with OCREVUS and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines.

Use in Specific Populations

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to OCREVUS during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-872-4370 or visiting www.ocrevuspregnancyregistry.com.

There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to OCREVUS. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier. 

Lactation 

There are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OCREVUS and any potential adverse effects on the breastfed infant from OCREVUS or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving OCREVUS and for 6 months after the last infusion of OCREVUS.

Most Common Adverse Reactions

RMS: The most common adverse reactions in RMS trials (incidence ≥10% and >REBIF) were upper respiratory tract infections (40%) and infusion reactions (34%).
 

PPMS: The most common adverse reactions in PPMS trials (incidence ≥10% and >placebo) were upper respiratory tract infections (49%), infusion reactions (40%), skin infections (14%), and lower respiratory tract infections (10%).

For additional safety information, please see the full Prescribing Information and Medication Guide.

¹ Murray TJ. (2006). Diagnosis and Treatment of Multiple Sclerosis. BMJ, 322 (7540):525-527.
² Tullman M. (2013). Overview of the Epidemiology, Diagnosis, and Disease Progression Associated With Multiple Sclerosis. The American Journal of Managed Care. 19 (2): S15-S20.
³ National Institutes of Health-National Institute of Neurological Disorders and Stroke. (2015). Multiple Sclerosis: Hope Through Research. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Multiple-Sclerosis-Hope-Through-Research.
⁴ National MS Society. "Who Gets MS? - African Americans." Retrieved November 2020. nationalmssociety.org/What-is-MS/Who-Gets-MS/African-American-Resources.
⁵ Langer-Gould A, et al. Neurology. 2013;80:1734-1739; 2. Wallin MT, et al. Brain. 2012;135:1778-1785.
⁶ U.S. Food and Drug Administration. “Clinical Trials Shed Light on Minority Health.” U.S. Food and Drug Administration Website. https://wayback.archive-it.org/7993/20180908114418/https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm349063.htm. Published 2018.
⁷ Genentech. “A New Perspective on Health Inequity.” https://www.gene.com/stories/a-new-perspective-on-health-inequity.

It’s undeniable that great strides have been made in advancing the science of multiple sclerosis (MS) over the past 20 years. Continued pursuit of research and discovery has revolutionized the understanding, diagnosis, and treatment of this debilitating condition that causes symptoms that may impact nearly every part of the body and mind. Despite these advancements, there is still more work to be done.

As the search for a cure continues, it’s imperative to ask the big questions: How does MS develop and progress? How can we reduce health disparities in care and treatment? How can we improve existing treatments and expedite the discovery of new ones? To continue making progress, we must stretch the boundaries of scientific understanding until we have answers and solutions to these and other important questions.

We know that MS is a leading cause of non-traumatic disability for young people.^1,2 Yet, one of the biggest challenges for neurologists is that every person’s experience with MS is unique, making it difficult to predict what symptoms will manifest, how disruptive the symptoms and relapses will be and how a person will respond to treatment.

Twenty years ago, it was widely thought that MS was mainly driven by T cells, but in the late 1990’s, a team of researchers made a groundbreaking discovery: B cells also played a key role in MS. This discovery redefined how the scientific community thought about the underlying biology of MS and the central role B cells can play. 

It was this bold thinking that led researchers at the University of California, San Francisco (UCSF) and scientists at Genentech, a member of the Roche Group, to explore whether a medication that depleted B cells would have an impact on MS. This collaboration, in turn, inspired the clinical research behind Ocrevus^® (ocrelizumab), the first and only treatment approved by the FDA for both relapsing MS (RMS) and primary progressive MS (PPMS). MS is a progressive disease from the start. An important goal of treating MS is to reduce disease progression as soon as possible to slow how quickly a person’s disability changes and prevent the long-term consequences of disease progression.³ Ocrevus is administered via infusion twice yearly, with the initial dose split into two separate infusions and given two weeks apart. As with any therapy, this treatment has side effects, which can be found in the full Prescribing Information and Medication Guide. Ocrevus is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reactions to Ocrevus. The warnings and precautions for Ocrevus are infusion reactions, and infections, which include respiratory tract infections, herpes, progressive multifocal leukoencephalopathy (PML), and hepatitis B virus (HBV) reactivation. Additional warnings are possible increased risk of immunosuppressant effects with other immunosuppressants, reduction in immunoglobulins, and malignancies.

Ensuring a Continuum of Care 
Another significant challenge facing the MS community is ensuring ongoing support and care for people living with the condition, especially throughout the COVID-19 pandemic. “We know that seeking early and appropriate care for MS is critical to slowing disability progression and achieving successful patient outcomes,” said Dr. Ashish Pradhan, Executive Director of Neuroimmunology at Genentech. “The pandemic has created additional barriers to early diagnosis and treatment, but we are committed to continuing to do everything we can to support patients and physicians at this stressful time.” Dr. Pradhan also observed that FDA's approval of a shorter infusion time for Ocrevus in December 2020 could potentially contribute to reducing some of the burden on the healthcare system in the long-term.

Being able to connect with others in the MS community is a vital part of navigating the uncertainties of living with the condition. This past April, to shine a light on the diverse MS community, Genentech hosted an #MSVisibility Virtual Concert that gathered people from across the world with different backgrounds and MS experiences and encouraged people living with MS to continue seeking appropriate support and care during the pandemic.

Continued support of the MS community through advocacy partnerships and grants over the years has played a sustained role in Genentech’s efforts to ensure people with MS receive necessary medical care and treatment. For example, Genentech partnered with an MS advocacy organization to fund a program that helps people get to and from their medical appointments. In addition, for more than 30 years, Genentech has helped more than two million people get the medicine they need through patient assistance programs like Genentech Access Solutions and the Genentech Patient Foundation.

Advancing Inclusive Research in MS 
MS has been shown to impact individuals and specific populations in markedly different ways. Those who identify as Black or of African descent and Hispanic/Latinos for example can experience more severe symptoms and faster disease progression than their Caucasian counterparts.^4,5 Unfortunately, it’s not clear exactly why, largely because of their vast underrepresentation in clinical trials (less than 5% and 1%, respectively).⁶ While there are multiple explanations for these disparities, around one-in-three minority patients don’t participate in clinical trials due to lack of trust and 52% feel that the healthcare system is not only flawed, but is actually working against them.⁷

“Increased diversity in research is paramount to ensuring that the healthcare system is serving every person living with MS and ultimately reducing health inequities while providing more tailored treatment options,” commented Dr. Pradhan. “To advance the care of undertreated and underserved people with MS, we are creating and supporting programs, grants and other initiatives focused on people of color and inclusive and minority research to better understand how MS presents itself and develops in different patient populations. We want to make sure that all generations of people living with MS are equally represented in clinical research and have access to the treatments that will work best for them.”

Refining Existing Approaches and Leading Treatment Innovation
For decades, Genentech and Roche have been conducting neuroscience research and clinical trials to make forward progress in understanding and treating a variety of neurological conditions, including MS. While the treatment landscape for MS has evolved significantly over the past two decades, continued investment in research and development is critical. Continuing to review and refine existing treatment approaches may improve patient outcomes and discovering new treatment approaches may play an important role in advancing the treatment paradigm.

Dr. Pradhan added, “as the scientific community continues to think boldly, and re-imagine treatment and care for MS, we hope to continue to improve our understanding of the condition for all people with the disease, and advance treatment options. Pushing boundaries means refusing to stop until everyone living with MS can be treated effectively and a cure is found. This sentiment reminds me of a Ralph Waldo Emerson quote, ‘Don’t follow where the path may lead. Go instead where there is no path and leave a trail.’ That’s what we are trying to do at Genentech.”

To learn more, please visit Ocrevus.com.

Indications and Important Safety Information
OCREVUS is indicated for the treatment of:

• Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
• Primary progressive MS, in adults. 

Contraindications
OCREVUS is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening infusion reaction to OCREVUS.

Warnings and Precautions

Infusion Reactions  

OCREVUS can cause infusion reactions, which can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis. In multiple sclerosis (MS) clinical trials, the incidence of infusion reactions in OCREVUS-treated patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to each infusion] was 34-40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of OCREVUS-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization.  

Observe patients treated with OCREVUS for infusion reactions during the infusion and for at least one hour after completion of the infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion. Administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered. For life-threatening infusion reactions, immediately and permanently stop OCREVUS and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of OCREVUS-treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS increased the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. OCREVUS was not associated with an increased risk of serious infections in MS patients. Delay OCREVUS administration in patients with an active infection until the infection is resolved.

Respiratory Tract Infections

A higher proportion of OCREVUS-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 43% of patients on placebo and 10% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.

Herpes

In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in OCREVUS-treated patients than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the OCREVUS-treated patients than in the patients on placebo (2.7% vs 0.8%).

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving OCREVUS. Serious herpes virus infections may occur at any time during treatment with OCREVUS. Some cases were life-threatening. 

If serious herpes infections occur, OCREVUS should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered.

Progressive Multifocal Leukoencephalopathy (PML)

PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no cases of PML were identified in OCREVUS clinical trials, JC virus infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies and has been associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). At the first sign or symptom suggestive of PML, withhold OCREVUS and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes (per USPI).

Hepatitis B Virus (HBV) Reactivation

Hepatitis B reactivation has been reported in MS patients treated with OCREVUS in the postmarketing setting. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with OCREVUS. Do not administer OCREVUS to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment.

Possible Increased Risk of Immunosuppressant Effects with Other Immunosuppressants

When initiating OCREVUS after an immunosuppressive therapy or initiating an immunosuppressive therapy after OCREVUS, consider the potential for increased immunosuppressive effect. OCREVUS has not been studied in combination with other MS therapies.

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines. OCREVUS may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following OCREVUS therapy has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated with OCREVUS During Pregnancy

In infants of mothers exposed to OCREVUS during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with OCREVUS treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during OCREVUS treatment and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing OCREVUS therapy in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Malignancies  

An increased risk of malignancy with OCREVUS may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in OCREVUS-treated patients. Breast cancer occurred in 6 of 781 females treated with OCREVUS and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines.

Use in Specific Populations

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy and fetal/neonatal/infant outcomes in women exposed to OCREVUS during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-833-872-4370 or visiting www.ocrevuspregnancyregistry.com.

There are no adequate data on the developmental risk associated with use of OCREVUS in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to OCREVUS. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. OCREVUS is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier. 

Lactation 

There are no data on the presence of ocrelizumab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OCREVUS and any potential adverse effects on the breastfed infant from OCREVUS or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving OCREVUS and for 6 months after the last infusion of OCREVUS.

Most Common Adverse Reactions

RMS: The most common adverse reactions in RMS trials (incidence ≥10% and >REBIF) were upper respiratory tract infections (40%) and infusion reactions (34%).
 

PPMS: The most common adverse reactions in PPMS trials (incidence ≥10% and >placebo) were upper respiratory tract infections (49%), infusion reactions (40%), skin infections (14%), and lower respiratory tract infections (10%).

For additional safety information, please see the full Prescribing Information and Medication Guide.

¹ Murray TJ. (2006). Diagnosis and Treatment of Multiple Sclerosis. BMJ, 322 (7540):525-527.
² Tullman M. (2013). Overview of the Epidemiology, Diagnosis, and Disease Progression Associated With Multiple Sclerosis. The American Journal of Managed Care. 19 (2): S15-S20.
³ National Institutes of Health-National Institute of Neurological Disorders and Stroke. (2015). Multiple Sclerosis: Hope Through Research. Available at: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Multiple-Sclerosis-Hope-Through-Research.
⁴ National MS Society. "Who Gets MS? - African Americans." Retrieved November 2020. nationalmssociety.org/What-is-MS/Who-Gets-MS/African-American-Resources.
⁵ Langer-Gould A, et al. Neurology. 2013;80:1734-1739; 2. Wallin MT, et al. Brain. 2012;135:1778-1785.
⁶ U.S. Food and Drug Administration. “Clinical Trials Shed Light on Minority Health.” U.S. Food and Drug Administration Website. https://wayback.archive-it.org/7993/20180908114418/https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm349063.htm. Published 2018.
⁷ Genentech. “A New Perspective on Health Inequity.” https://www.gene.com/stories/a-new-perspective-on-health-inequity.

A new study has found that physical therapy may lead to a reduced risk of long-term opioid use in patients who have undergone total knee replacement (TKR).

ChooChin/Getty Images

“Greater number of PT intervention sessions and earlier initiation of outpatient PT care after TKR were associated with lower odds of long-term opioid use,” authors from Boston University wrote in their report on the study, which was published online Oct. 27 in JAMA Network Open.

“In previous large studies, we’ve seen that physical therapy can reduce pain in people with knee osteoarthritis, which is usually the primary indication for TKR,” study coauthor Deepak Kumar, PT, PhD, said in an interview. “But the association of physical therapy with opioid use in people with knee replacement has not yet been explored.

“The reason we focused on opioid use in these patients is because the number of knee replacement surgeries is going up exponentially,” Dr. Kumar said. “And, depending on which data you look at, from one-third to up to half of people who undergo knee replacement and have used opioids before end up becoming long-term users. Even in people who have not used them before, 5%-8% become long-term users after the surgery.

“Given how many surgeries are happening – and that number is expected to keep going up – the number of people who are becoming long-term opioid users is not trivial,” he said.
 

Study details

To assess the value of PT in reducing opioid use in this subset of patients, the authors reviewed records from the OptumLabs Data Warehouse insurance claims database to identify 67,322 eligible participants aged 40 or older who underwent TKR from Jan. 1, 2001, to Dec. 31, 2016. Of those patients, 38,408 were opioid naive and 28,914 had taken opioids before. The authors evaluated long-term opioid use – defined as 90 days or more of filled prescriptions – during a 12-month outcome assessment period that varied depending on differences in post-TKR PT start date and duration.

The researchers found a significantly lower likelihood of long-term opioid use associated with receipt of any PT before TKR among patients who had not taken opioids before (adjusted odds ratio [aOR], 0.75; 95% confidence interval, 0.60-0.95) and those who had taken opioids in the past (aOR, 0.75; 95% CI, 0.70-0.80).

Investigators found that 2.2% of participants in the opioid-naive group and 32.5% of those in the opioid-experienced group used opioids long-term after TKR. Approximately 76% of participants overall received outpatient PT within the 90 days after surgery, and the receipt of post-TKR PT at any point was associated with lower odds of long-term opioid use in the opioid-experienced group (aOR, 0.75; 95% CI, 0.70-0.79).

Among the opioid-experienced group, receiving between 6 and 12 PT sessions (aOR, 0.82; 95% CI, 0.75-0.90) or ≥ 13 sessions (aOR, 0.71; 95% CI, 0.65-0.77) were both associated with lower odds of long-term opioid use, compared with those who received 1-5 sessions. Beginning PT 31-60 days or 61-90 days after surgery was associated with greater odds of long-term opioid use across both cohorts, compared with those who initiated therapy within 30 days of TKR.
 

Physical therapy: Underexplored option for pain in knee replacement

One finding caught the researchers slightly off guard: There was no association between active physical therapy and reduced odds of long-term opioid use. “From prior studies, at least in people with knee osteoarthritis, we know that active interventions were more useful than passive interventions,” Dr. Kumar said.

That said, he added that there is still some professional uncertainty regarding “the right type or the right components of physical therapy for managing pain in this population.” Regardless, he believes their study emphasizes the benefits of PT as a pain alleviator in these patients, especially those who have previously used opioids.

“Pharmaceuticals have side effects. Injections are not super effective,” he said. “The idea behind focusing on physical therapy interventions is that it’s widely available, it does you no harm, and it could potentially be lower cost to both the payers and the providers.”

The authors acknowledged their study’s limitations, including not adjusting for opioid use within the 90 days after surgery as well as the different outcome assessment periods for pre-TKR and post-TKR PT exposures. In addition, they admitted that some of the patients who received PT could have been among those less likely to be treated with opioids, and vice versa. “A randomized clinical trial,” they wrote, “would be required to disentangle these issues.”

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Kumar reported receiving grants from the National Institutes of Health during the conduct of the study and grants from Pfizer for unrelated projects outside the submitted work. The full list of author disclosures can be found with the original article.

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

A new study has found that physical therapy may lead to a reduced risk of long-term opioid use in patients who have undergone total knee replacement (TKR).

ChooChin/Getty Images

“Greater number of PT intervention sessions and earlier initiation of outpatient PT care after TKR were associated with lower odds of long-term opioid use,” authors from Boston University wrote in their report on the study, which was published online Oct. 27 in JAMA Network Open.

“In previous large studies, we’ve seen that physical therapy can reduce pain in people with knee osteoarthritis, which is usually the primary indication for TKR,” study coauthor Deepak Kumar, PT, PhD, said in an interview. “But the association of physical therapy with opioid use in people with knee replacement has not yet been explored.

“The reason we focused on opioid use in these patients is because the number of knee replacement surgeries is going up exponentially,” Dr. Kumar said. “And, depending on which data you look at, from one-third to up to half of people who undergo knee replacement and have used opioids before end up becoming long-term users. Even in people who have not used them before, 5%-8% become long-term users after the surgery.

“Given how many surgeries are happening – and that number is expected to keep going up – the number of people who are becoming long-term opioid users is not trivial,” he said.
 

Study details

To assess the value of PT in reducing opioid use in this subset of patients, the authors reviewed records from the OptumLabs Data Warehouse insurance claims database to identify 67,322 eligible participants aged 40 or older who underwent TKR from Jan. 1, 2001, to Dec. 31, 2016. Of those patients, 38,408 were opioid naive and 28,914 had taken opioids before. The authors evaluated long-term opioid use – defined as 90 days or more of filled prescriptions – during a 12-month outcome assessment period that varied depending on differences in post-TKR PT start date and duration.

The researchers found a significantly lower likelihood of long-term opioid use associated with receipt of any PT before TKR among patients who had not taken opioids before (adjusted odds ratio [aOR], 0.75; 95% confidence interval, 0.60-0.95) and those who had taken opioids in the past (aOR, 0.75; 95% CI, 0.70-0.80).

Investigators found that 2.2% of participants in the opioid-naive group and 32.5% of those in the opioid-experienced group used opioids long-term after TKR. Approximately 76% of participants overall received outpatient PT within the 90 days after surgery, and the receipt of post-TKR PT at any point was associated with lower odds of long-term opioid use in the opioid-experienced group (aOR, 0.75; 95% CI, 0.70-0.79).

Among the opioid-experienced group, receiving between 6 and 12 PT sessions (aOR, 0.82; 95% CI, 0.75-0.90) or ≥ 13 sessions (aOR, 0.71; 95% CI, 0.65-0.77) were both associated with lower odds of long-term opioid use, compared with those who received 1-5 sessions. Beginning PT 31-60 days or 61-90 days after surgery was associated with greater odds of long-term opioid use across both cohorts, compared with those who initiated therapy within 30 days of TKR.
 

Physical therapy: Underexplored option for pain in knee replacement

One finding caught the researchers slightly off guard: There was no association between active physical therapy and reduced odds of long-term opioid use. “From prior studies, at least in people with knee osteoarthritis, we know that active interventions were more useful than passive interventions,” Dr. Kumar said.

That said, he added that there is still some professional uncertainty regarding “the right type or the right components of physical therapy for managing pain in this population.” Regardless, he believes their study emphasizes the benefits of PT as a pain alleviator in these patients, especially those who have previously used opioids.

“Pharmaceuticals have side effects. Injections are not super effective,” he said. “The idea behind focusing on physical therapy interventions is that it’s widely available, it does you no harm, and it could potentially be lower cost to both the payers and the providers.”

The authors acknowledged their study’s limitations, including not adjusting for opioid use within the 90 days after surgery as well as the different outcome assessment periods for pre-TKR and post-TKR PT exposures. In addition, they admitted that some of the patients who received PT could have been among those less likely to be treated with opioids, and vice versa. “A randomized clinical trial,” they wrote, “would be required to disentangle these issues.”

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Kumar reported receiving grants from the National Institutes of Health during the conduct of the study and grants from Pfizer for unrelated projects outside the submitted work. The full list of author disclosures can be found with the original article.

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

A new study has found that physical therapy may lead to a reduced risk of long-term opioid use in patients who have undergone total knee replacement (TKR).

ChooChin/Getty Images

“Greater number of PT intervention sessions and earlier initiation of outpatient PT care after TKR were associated with lower odds of long-term opioid use,” authors from Boston University wrote in their report on the study, which was published online Oct. 27 in JAMA Network Open.

“In previous large studies, we’ve seen that physical therapy can reduce pain in people with knee osteoarthritis, which is usually the primary indication for TKR,” study coauthor Deepak Kumar, PT, PhD, said in an interview. “But the association of physical therapy with opioid use in people with knee replacement has not yet been explored.

“The reason we focused on opioid use in these patients is because the number of knee replacement surgeries is going up exponentially,” Dr. Kumar said. “And, depending on which data you look at, from one-third to up to half of people who undergo knee replacement and have used opioids before end up becoming long-term users. Even in people who have not used them before, 5%-8% become long-term users after the surgery.

“Given how many surgeries are happening – and that number is expected to keep going up – the number of people who are becoming long-term opioid users is not trivial,” he said.
 

Study details

To assess the value of PT in reducing opioid use in this subset of patients, the authors reviewed records from the OptumLabs Data Warehouse insurance claims database to identify 67,322 eligible participants aged 40 or older who underwent TKR from Jan. 1, 2001, to Dec. 31, 2016. Of those patients, 38,408 were opioid naive and 28,914 had taken opioids before. The authors evaluated long-term opioid use – defined as 90 days or more of filled prescriptions – during a 12-month outcome assessment period that varied depending on differences in post-TKR PT start date and duration.

The researchers found a significantly lower likelihood of long-term opioid use associated with receipt of any PT before TKR among patients who had not taken opioids before (adjusted odds ratio [aOR], 0.75; 95% confidence interval, 0.60-0.95) and those who had taken opioids in the past (aOR, 0.75; 95% CI, 0.70-0.80).

Investigators found that 2.2% of participants in the opioid-naive group and 32.5% of those in the opioid-experienced group used opioids long-term after TKR. Approximately 76% of participants overall received outpatient PT within the 90 days after surgery, and the receipt of post-TKR PT at any point was associated with lower odds of long-term opioid use in the opioid-experienced group (aOR, 0.75; 95% CI, 0.70-0.79).

Among the opioid-experienced group, receiving between 6 and 12 PT sessions (aOR, 0.82; 95% CI, 0.75-0.90) or ≥ 13 sessions (aOR, 0.71; 95% CI, 0.65-0.77) were both associated with lower odds of long-term opioid use, compared with those who received 1-5 sessions. Beginning PT 31-60 days or 61-90 days after surgery was associated with greater odds of long-term opioid use across both cohorts, compared with those who initiated therapy within 30 days of TKR.
 

Physical therapy: Underexplored option for pain in knee replacement

One finding caught the researchers slightly off guard: There was no association between active physical therapy and reduced odds of long-term opioid use. “From prior studies, at least in people with knee osteoarthritis, we know that active interventions were more useful than passive interventions,” Dr. Kumar said.

That said, he added that there is still some professional uncertainty regarding “the right type or the right components of physical therapy for managing pain in this population.” Regardless, he believes their study emphasizes the benefits of PT as a pain alleviator in these patients, especially those who have previously used opioids.

“Pharmaceuticals have side effects. Injections are not super effective,” he said. “The idea behind focusing on physical therapy interventions is that it’s widely available, it does you no harm, and it could potentially be lower cost to both the payers and the providers.”

The authors acknowledged their study’s limitations, including not adjusting for opioid use within the 90 days after surgery as well as the different outcome assessment periods for pre-TKR and post-TKR PT exposures. In addition, they admitted that some of the patients who received PT could have been among those less likely to be treated with opioids, and vice versa. “A randomized clinical trial,” they wrote, “would be required to disentangle these issues.”

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Kumar reported receiving grants from the National Institutes of Health during the conduct of the study and grants from Pfizer for unrelated projects outside the submitted work. The full list of author disclosures can be found with the original article.

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