Clinical Endocrinology News

By the time she was discharged from a suburban New Jersey hospital on April 10, Kathleen Ronan thought the worst was behind her. For a week before her husband rushed her to the emergency department (ED), incoherent and struggling to breathe, the novel coronavirus had ravaged her body. She tried to treat her fevers with acetaminophen and ice packs. Despite taking enough Tylenol to risk liver damage and packing herself on ice like the catch of the day, Ronan’s fever continued to rise. By the time her temperature reached 104.5° F, Ronan knew the time had come for more drastic measures.

A team of masked and gowned nurses greeted her at a triage tent outside the ED, and from there, everything becomes hazy for Ronan. She was immediately rushed to the hospital’s special COVID-19 intensive care unit (ICU), where she spent 5 days. But she has few distinct memories from this time. What she does remember is the exhaustion, the pain, the loneliness, and the fear. Her family couldn’t visit, and though Ronan works as a home health nurse, her brain was so addled with fever that she couldn’t make sense of what was happening. After a week in the hospital, 5 days of which were spent in the ICU, 51-year-old Ronan was discharged.

Her years of working as a home health nurse told her that the return home wouldn’t be easy, but nothing prepared her for just how much she would struggle. The once-active Ronan, who had supplemented long days on her feet caring for others as a nurse with regular trips to the gym, now needed a walker to traverse the few steps from her bed to the toilet, an effort that left her gasping for air. Her brain couldn’t even focus on an audiobook, let alone a short magazine article.

“It just completely knocked the stuffing out of me,” Ronan said.

Ronan’s lingering symptoms aren’t unique to COVID-19 patients. In as many as 80% of patients leaving the ICU, researchers have documented what they call post–intensive care syndrome (PICS) — a constellation of physical, cognitive, and psychiatric symptoms that result from an ICU stay. Although underlying illness plays a role in these symptoms, the amount of time spent in critical care is a major factor.

Nor is PICS simply a set of side effects that will go away on their own. It includes ongoing cognitive difficulties and physical weakness, both of which can lead to employment problems. Beyond that, depression and anxiety can exacerbate – and be exacerbated by – these challenges. Psychologist Jim Jackson, PsyD, assistant director of the ICU Recovery Center at Vanderbilt University Medical Center, Nashville, Tennessee, recently spoke with a former ICU patient who has struggled since her discharge 30 years ago.

“Her life essentially stopped with her critical care stay. She hasn’t been able to move forward,” he said. “She’s part of a whole fraternity of people who are struggling.”

The good news is that over the past decade, researchers have made important strides in understanding what makes PICS symptoms worse and how critical care physicians can tweak ICU protocols to reduce PICS severity. Practitioners will need to draw on this knowledge to help Ronan and the thousands of COVID-19 ICU patients like her.
 

Surviving the ICU

Although the new coronavirus has pushed the world’s critical care system to its limits, it was an outbreak in 1952 that inspired the creation of intensive care units. That summer, a wave of paralytic polio swept over Copenhagen, Denmark, and anesthesiologist Bjørn Ibsen, MD, PhD, used mechanical ventilation — physically operated by medical and dental students – to help 316 children breathe for weeks at a time while their small bodies worked to fight off the virus. The effort halved the mortality rate from polio that affected breathing, from 80% to 40%.

In these wards, dedicated to the very sickest, each patient was assigned his or her own nurse. Over the next decade, hospitals in the United Kingdom and the United States established their own ICUs to treat patients with a variety of conditions. Although it helped improve survival, mortality rates in critical care units remained stubbornly high, owing to the patients’ severe underlying illnesses.

“We thought we were doing a good job if the patient survived, but we had no idea what happened after discharge,” said Carla Sevin, MD, medical director of Vanderbilt’s ICU Recovery Center. Nor did their efforts to find out always bring answers. “We struggled to get people to come in for support — they were debilitated, physically burdened, and weak.”

Through further advances in life support, by the early 2000s, the average mortality rates in American ICUs had dropped to 8% to 19%. As the number of critical care survivors began to climb, clinical researchers noticed that the lives of these patients and their families were profoundly altered by their severe illness.

As Dale Needham, MD, PhD, began his pulmonology and critical care residency in Toronto, Canada, in 2005, a group of physicians there began a 5-year longitudinal study to assess long-term outcomes of patients who developed acute respiratory distress syndrome (ARDS). Although ARDS is an acute condition, the investigators found that patients felt effects for years. Younger patients recovered better than older ones, but none of the patients› physical functioning was equivalent to that of age-matched control persons. Even 5 years later, former ICU patients only reached 76% of expected physical functioning, according to results published in the New England Journal of Medicine. The study was a wake-up call.

At a meeting in Chicago in 2010, Needham, now an intensivist at Johns Hopkins Hospital in Baltimore, Maryland, gathered an interdisciplinary group of colleagues, including patients and caregivers, to clarify the phenomena they were seeing. What emerged from that meeting, published in 2012 in Critical Care Medicine, were the diagnostic criteria for PICS: According to the new definition, PICS is characterized by new or worsening physical and neuropsychiatric deficits that range from forgetfulness and loss of motivation to physical weakness and insomnia.

The issue, Needham says, is that although the trouble starts in the ICU, it only becomes clear once patients leave. “ICU doctors aren’t the ones dealing with this,” Needham said. “We need to build stronger bridges between critical care and other professions.” That’s where PICS comes in, a definition that exists explicitly to alert healthcare providers about the constellation of challenges many of these individuals face as they try to reenter “normal” life.
 

Defining the problem

As an ICU nurse at the Mayo Clinic in Rochester, Minnesota, Annie Johnson, ACNP-BC, knew lots about helping hospitalized patients, but she says she didn’t know anything about what to do after discharge – at least not until her own mother became a patient.

On the first day of retirement in October 2014, Johnson’s mother flatlined. Quick-thinking paramedics resuscitated her, and after several days in critical care, she was discharged. Since then, her heart has remained healthy. Johnson’s sister, who spent time worrying over her mother at the hospital, also had lingering effects. Both have since struggled, plagued by nightmares, flashbacks, and insomnia.

Johnson initially believed her mom’s and sister’s neuropsychiatric, post-ICU struggles were unique to her family. It was only a year later, at a seminar she was attending, that she first heard the words “post–intensive care syndrome.” Suddenly, Johnson had a name for her family’s experiences, and she began to create support groups and resources to help other families like hers.

“I thought of all the patients I had treated over the years who had been on ventilators for days and days and days. And if this happened to my mom after 48 hours, what must they be going through?” she asked.

Once physicians formally defined PICS, the Society for Critical Care Medicine helped create programs to educate ICU staff, patients, and families about potential post-discharge challenges. Researchers also began to investigate factors affecting post-ICU functioning. Follow-up studies of patients with delirium (ranging from general confusion about time and place to extreme agitation and violence) showed they had striking cognitive deficits. Problems with short-term memory, flexible thinking, and motivation plagued patients for years after their critical illness, similar to the physical deficiencies seen after ARDS. Delirium was one of the strongest risk factors for neuropsychiatric problems.

“Delirium is basically a stress test for the brain,” said Babar Khan, MD, a critical care specialist at Indiana University’s Regenstrief Institute, in Bloomington. But whether delirium accentuates preexisting cognitive difficulties or creates them afresh isn’t yet clear.

Sophia Wang, MD, a geriatric psychiatrist at Indiana University who works with many critical care patients, says patients who had experienced delirium in the ICU showed significant defects in memory and executive functioning long after their hospital stay. She points to a 2015 study that followed 47 ICU patients for a year post discharge. Among those who experienced delirium, brain volumes, as measured by MRI, were smaller at 3 months, something associated with cognitive problems at 1 year. Many struggled at work, and unemployment was common. Depression and posttraumatic stress compounded these difficulties. Among those with acute respiratory distress, ICU patients who are young, female, and unemployed are most likely to suffer from posttraumatic stress disorder after they are discharge.

Critical care medicine may have given these patients a second chance at life, Wang says, but the life they return to often looks nothing like the one they had before their illness.

Prolonged mechanical ventilation and the heavy sedation that often accompanies it are predictors of PICS severity. Some of these links could be explained by the gravity of the illness that landed someone in critical care, but others are more likely to be iatrogenic, says Gerald Weinhouse, MD, a pulmonology and critical care physician and co-director of the Critical Illness Recovery Program at the Brigham and Women’s Hospital in Boston. The involvement of loved ones at the patient’s bedside, however, improved the entire family’s outcome.

When Weinhouse saw those data, he and his colleagues founded a peer support program for ICU survivors. In a study published in 2019 in Critical Care Medicine, they identified six different models for peer support for those with PICS and their families, including both online and in-person approaches. An ongoing challenge for physicians, Weinhouse says, is getting patients to engage with these programs, given that their calendars are crowded with medical appointments and that they suffer from increased physical and mental disability.

Studies such as these led critical care physicians to form the ICU Liberation Collaborative to rethink critical care medicine. At Vanderbilt, Sevin and Jackson headed up one of the world’s first post-ICU clinics, which uses an interdisciplinary team to help patients maximize their functioning. They redesigned their critical care unit in a way that allows families to spend the night and that encourages patient mobility. Both Needham and Weinhouse continue tracking patient outcomes.

Even before the novel coronavirus struck, the United States — and the world — had begun to realize that graduating from the ICU was only the start of what was often an extensive recovery.
 

The long road back

When COVID-19 patients began flooding intensive care wards around the world, physicians scrambled to meet their complex and desperate acute medical needs. Over the past few months, physicians have focused on keeping these patients alive. “We’ve never seen anything like it ― not even during polio — with the sheer number of patients, all with respiratory distress,” Needham said.

But he and his colleagues know this is only the beginning.

“We’re aware that survivorship issues are coming. There’s going to be a wave of sick people who survived the coronavirus but are going to need more help,” Weinhouse said.

Intensivists have been drawing on PICS research in their fight to help COVID-19 patients. Work from the past few years has shown that although sedation is required during intubation itself, not everyone needs it while on a ventilator. Titrating down sedating medication helps reduce delirium, Wang says. Such medication has been shown to contribute to later cognitive problems. Needham’s studies showing that prolonged bedrest by ICU patients causes muscular atrophy has led him to encourage patients to move as much as possible. With the help of physical therapists, many patients on ventilators can be awake, alert, and moving around the ward.

One of the biggest challenges critical-care coronavirus patients face is prolonged isolation. The constant presence of a familiar face helps orient confused and delirious patients and provides emotional support during a frightening time. But because the immediate need for infection control outweighs these benefits, few hospitals allow visitors, especially for COVID-19 patients.

To address this, some units have been using video technology to allow loved ones to call in. At Johns Hopkins, physicians have also been relying on the expertise of occupational therapists (OTs). Needham says that one OT found that rubbing the hand and back of an agitated, delirious patient helped soothe and calm him better than many medications.

Ronan, who spent 5 days in intensive care, echoes that problem. She says she found the relative lack of human contact to be one of the most challenging parts of being in a bed on a COVID-19 ward. Separated from her husband and daughter, suffering from high fever and severe illness, she lost all track of time.

Her return home was difficult, too. Although her job as a home health nurse had prepared her on some level for the challenges she would face after discharge, Ronan says the hospital provided little practical help.

“Everything is so much harder at home, even little things like going to the bathroom,” she said. “I feel like I’m trying to bail out a sinking ship with a teacup.”

Khan and other physicians, aware of the challenges Ronan and others face once home, aim to create post-ICU clinics specifically for COVID-19 patients. They want to build what Khan calls a “one-stop shop” for all the support patients need to recover. Some of that can be provided via telehealth, which may also help ease the physical burden.

Because there’s so much physicians don’t know about the coronavirus, Johnson says, such clinics are not only a chance to help the sickest COVID-19 patients, they will also help researchers learn more about the virus and improve critical care for other illnesses.

Today, nearly 2 months after discharge, Ronan is back on the job but struggles with a persistent cough — likely due to the lung damage she sustained while ill. She has constant fatigue, as well as ongoing upset stomach from all the medications she took to reduce fever and body aches. When she dons a mask for work, the tangible reminder of her hospital stay sends her into a panic attack. Physically, she’s weaker than before.

Researchers are still trying to understand everything that Ronan and other COVID-19 patients need to move on with their lives after being in the ICU. Mysteries abound, but the ground laid by Sevin, Needham, Weinhouse, and others has provided a solid foundation on which to build.
 

This article first appeared on Medscape.com.

By the time she was discharged from a suburban New Jersey hospital on April 10, Kathleen Ronan thought the worst was behind her. For a week before her husband rushed her to the emergency department (ED), incoherent and struggling to breathe, the novel coronavirus had ravaged her body. She tried to treat her fevers with acetaminophen and ice packs. Despite taking enough Tylenol to risk liver damage and packing herself on ice like the catch of the day, Ronan’s fever continued to rise. By the time her temperature reached 104.5° F, Ronan knew the time had come for more drastic measures.

A team of masked and gowned nurses greeted her at a triage tent outside the ED, and from there, everything becomes hazy for Ronan. She was immediately rushed to the hospital’s special COVID-19 intensive care unit (ICU), where she spent 5 days. But she has few distinct memories from this time. What she does remember is the exhaustion, the pain, the loneliness, and the fear. Her family couldn’t visit, and though Ronan works as a home health nurse, her brain was so addled with fever that she couldn’t make sense of what was happening. After a week in the hospital, 5 days of which were spent in the ICU, 51-year-old Ronan was discharged.

Her years of working as a home health nurse told her that the return home wouldn’t be easy, but nothing prepared her for just how much she would struggle. The once-active Ronan, who had supplemented long days on her feet caring for others as a nurse with regular trips to the gym, now needed a walker to traverse the few steps from her bed to the toilet, an effort that left her gasping for air. Her brain couldn’t even focus on an audiobook, let alone a short magazine article.

“It just completely knocked the stuffing out of me,” Ronan said.

Ronan’s lingering symptoms aren’t unique to COVID-19 patients. In as many as 80% of patients leaving the ICU, researchers have documented what they call post–intensive care syndrome (PICS) — a constellation of physical, cognitive, and psychiatric symptoms that result from an ICU stay. Although underlying illness plays a role in these symptoms, the amount of time spent in critical care is a major factor.

Nor is PICS simply a set of side effects that will go away on their own. It includes ongoing cognitive difficulties and physical weakness, both of which can lead to employment problems. Beyond that, depression and anxiety can exacerbate – and be exacerbated by – these challenges. Psychologist Jim Jackson, PsyD, assistant director of the ICU Recovery Center at Vanderbilt University Medical Center, Nashville, Tennessee, recently spoke with a former ICU patient who has struggled since her discharge 30 years ago.

“Her life essentially stopped with her critical care stay. She hasn’t been able to move forward,” he said. “She’s part of a whole fraternity of people who are struggling.”

The good news is that over the past decade, researchers have made important strides in understanding what makes PICS symptoms worse and how critical care physicians can tweak ICU protocols to reduce PICS severity. Practitioners will need to draw on this knowledge to help Ronan and the thousands of COVID-19 ICU patients like her.
 

Surviving the ICU

Although the new coronavirus has pushed the world’s critical care system to its limits, it was an outbreak in 1952 that inspired the creation of intensive care units. That summer, a wave of paralytic polio swept over Copenhagen, Denmark, and anesthesiologist Bjørn Ibsen, MD, PhD, used mechanical ventilation — physically operated by medical and dental students – to help 316 children breathe for weeks at a time while their small bodies worked to fight off the virus. The effort halved the mortality rate from polio that affected breathing, from 80% to 40%.

In these wards, dedicated to the very sickest, each patient was assigned his or her own nurse. Over the next decade, hospitals in the United Kingdom and the United States established their own ICUs to treat patients with a variety of conditions. Although it helped improve survival, mortality rates in critical care units remained stubbornly high, owing to the patients’ severe underlying illnesses.

“We thought we were doing a good job if the patient survived, but we had no idea what happened after discharge,” said Carla Sevin, MD, medical director of Vanderbilt’s ICU Recovery Center. Nor did their efforts to find out always bring answers. “We struggled to get people to come in for support — they were debilitated, physically burdened, and weak.”

Through further advances in life support, by the early 2000s, the average mortality rates in American ICUs had dropped to 8% to 19%. As the number of critical care survivors began to climb, clinical researchers noticed that the lives of these patients and their families were profoundly altered by their severe illness.

As Dale Needham, MD, PhD, began his pulmonology and critical care residency in Toronto, Canada, in 2005, a group of physicians there began a 5-year longitudinal study to assess long-term outcomes of patients who developed acute respiratory distress syndrome (ARDS). Although ARDS is an acute condition, the investigators found that patients felt effects for years. Younger patients recovered better than older ones, but none of the patients› physical functioning was equivalent to that of age-matched control persons. Even 5 years later, former ICU patients only reached 76% of expected physical functioning, according to results published in the New England Journal of Medicine. The study was a wake-up call.

At a meeting in Chicago in 2010, Needham, now an intensivist at Johns Hopkins Hospital in Baltimore, Maryland, gathered an interdisciplinary group of colleagues, including patients and caregivers, to clarify the phenomena they were seeing. What emerged from that meeting, published in 2012 in Critical Care Medicine, were the diagnostic criteria for PICS: According to the new definition, PICS is characterized by new or worsening physical and neuropsychiatric deficits that range from forgetfulness and loss of motivation to physical weakness and insomnia.

The issue, Needham says, is that although the trouble starts in the ICU, it only becomes clear once patients leave. “ICU doctors aren’t the ones dealing with this,” Needham said. “We need to build stronger bridges between critical care and other professions.” That’s where PICS comes in, a definition that exists explicitly to alert healthcare providers about the constellation of challenges many of these individuals face as they try to reenter “normal” life.
 

Defining the problem

As an ICU nurse at the Mayo Clinic in Rochester, Minnesota, Annie Johnson, ACNP-BC, knew lots about helping hospitalized patients, but she says she didn’t know anything about what to do after discharge – at least not until her own mother became a patient.

On the first day of retirement in October 2014, Johnson’s mother flatlined. Quick-thinking paramedics resuscitated her, and after several days in critical care, she was discharged. Since then, her heart has remained healthy. Johnson’s sister, who spent time worrying over her mother at the hospital, also had lingering effects. Both have since struggled, plagued by nightmares, flashbacks, and insomnia.

Johnson initially believed her mom’s and sister’s neuropsychiatric, post-ICU struggles were unique to her family. It was only a year later, at a seminar she was attending, that she first heard the words “post–intensive care syndrome.” Suddenly, Johnson had a name for her family’s experiences, and she began to create support groups and resources to help other families like hers.

“I thought of all the patients I had treated over the years who had been on ventilators for days and days and days. And if this happened to my mom after 48 hours, what must they be going through?” she asked.

Once physicians formally defined PICS, the Society for Critical Care Medicine helped create programs to educate ICU staff, patients, and families about potential post-discharge challenges. Researchers also began to investigate factors affecting post-ICU functioning. Follow-up studies of patients with delirium (ranging from general confusion about time and place to extreme agitation and violence) showed they had striking cognitive deficits. Problems with short-term memory, flexible thinking, and motivation plagued patients for years after their critical illness, similar to the physical deficiencies seen after ARDS. Delirium was one of the strongest risk factors for neuropsychiatric problems.

“Delirium is basically a stress test for the brain,” said Babar Khan, MD, a critical care specialist at Indiana University’s Regenstrief Institute, in Bloomington. But whether delirium accentuates preexisting cognitive difficulties or creates them afresh isn’t yet clear.

Sophia Wang, MD, a geriatric psychiatrist at Indiana University who works with many critical care patients, says patients who had experienced delirium in the ICU showed significant defects in memory and executive functioning long after their hospital stay. She points to a 2015 study that followed 47 ICU patients for a year post discharge. Among those who experienced delirium, brain volumes, as measured by MRI, were smaller at 3 months, something associated with cognitive problems at 1 year. Many struggled at work, and unemployment was common. Depression and posttraumatic stress compounded these difficulties. Among those with acute respiratory distress, ICU patients who are young, female, and unemployed are most likely to suffer from posttraumatic stress disorder after they are discharge.

Critical care medicine may have given these patients a second chance at life, Wang says, but the life they return to often looks nothing like the one they had before their illness.

Prolonged mechanical ventilation and the heavy sedation that often accompanies it are predictors of PICS severity. Some of these links could be explained by the gravity of the illness that landed someone in critical care, but others are more likely to be iatrogenic, says Gerald Weinhouse, MD, a pulmonology and critical care physician and co-director of the Critical Illness Recovery Program at the Brigham and Women’s Hospital in Boston. The involvement of loved ones at the patient’s bedside, however, improved the entire family’s outcome.

When Weinhouse saw those data, he and his colleagues founded a peer support program for ICU survivors. In a study published in 2019 in Critical Care Medicine, they identified six different models for peer support for those with PICS and their families, including both online and in-person approaches. An ongoing challenge for physicians, Weinhouse says, is getting patients to engage with these programs, given that their calendars are crowded with medical appointments and that they suffer from increased physical and mental disability.

Studies such as these led critical care physicians to form the ICU Liberation Collaborative to rethink critical care medicine. At Vanderbilt, Sevin and Jackson headed up one of the world’s first post-ICU clinics, which uses an interdisciplinary team to help patients maximize their functioning. They redesigned their critical care unit in a way that allows families to spend the night and that encourages patient mobility. Both Needham and Weinhouse continue tracking patient outcomes.

Even before the novel coronavirus struck, the United States — and the world — had begun to realize that graduating from the ICU was only the start of what was often an extensive recovery.
 

The long road back

When COVID-19 patients began flooding intensive care wards around the world, physicians scrambled to meet their complex and desperate acute medical needs. Over the past few months, physicians have focused on keeping these patients alive. “We’ve never seen anything like it ― not even during polio — with the sheer number of patients, all with respiratory distress,” Needham said.

But he and his colleagues know this is only the beginning.

“We’re aware that survivorship issues are coming. There’s going to be a wave of sick people who survived the coronavirus but are going to need more help,” Weinhouse said.

Intensivists have been drawing on PICS research in their fight to help COVID-19 patients. Work from the past few years has shown that although sedation is required during intubation itself, not everyone needs it while on a ventilator. Titrating down sedating medication helps reduce delirium, Wang says. Such medication has been shown to contribute to later cognitive problems. Needham’s studies showing that prolonged bedrest by ICU patients causes muscular atrophy has led him to encourage patients to move as much as possible. With the help of physical therapists, many patients on ventilators can be awake, alert, and moving around the ward.

One of the biggest challenges critical-care coronavirus patients face is prolonged isolation. The constant presence of a familiar face helps orient confused and delirious patients and provides emotional support during a frightening time. But because the immediate need for infection control outweighs these benefits, few hospitals allow visitors, especially for COVID-19 patients.

To address this, some units have been using video technology to allow loved ones to call in. At Johns Hopkins, physicians have also been relying on the expertise of occupational therapists (OTs). Needham says that one OT found that rubbing the hand and back of an agitated, delirious patient helped soothe and calm him better than many medications.

Ronan, who spent 5 days in intensive care, echoes that problem. She says she found the relative lack of human contact to be one of the most challenging parts of being in a bed on a COVID-19 ward. Separated from her husband and daughter, suffering from high fever and severe illness, she lost all track of time.

Her return home was difficult, too. Although her job as a home health nurse had prepared her on some level for the challenges she would face after discharge, Ronan says the hospital provided little practical help.

“Everything is so much harder at home, even little things like going to the bathroom,” she said. “I feel like I’m trying to bail out a sinking ship with a teacup.”

Khan and other physicians, aware of the challenges Ronan and others face once home, aim to create post-ICU clinics specifically for COVID-19 patients. They want to build what Khan calls a “one-stop shop” for all the support patients need to recover. Some of that can be provided via telehealth, which may also help ease the physical burden.

Because there’s so much physicians don’t know about the coronavirus, Johnson says, such clinics are not only a chance to help the sickest COVID-19 patients, they will also help researchers learn more about the virus and improve critical care for other illnesses.

Today, nearly 2 months after discharge, Ronan is back on the job but struggles with a persistent cough — likely due to the lung damage she sustained while ill. She has constant fatigue, as well as ongoing upset stomach from all the medications she took to reduce fever and body aches. When she dons a mask for work, the tangible reminder of her hospital stay sends her into a panic attack. Physically, she’s weaker than before.

Researchers are still trying to understand everything that Ronan and other COVID-19 patients need to move on with their lives after being in the ICU. Mysteries abound, but the ground laid by Sevin, Needham, Weinhouse, and others has provided a solid foundation on which to build.
 

This article first appeared on Medscape.com.

By the time she was discharged from a suburban New Jersey hospital on April 10, Kathleen Ronan thought the worst was behind her. For a week before her husband rushed her to the emergency department (ED), incoherent and struggling to breathe, the novel coronavirus had ravaged her body. She tried to treat her fevers with acetaminophen and ice packs. Despite taking enough Tylenol to risk liver damage and packing herself on ice like the catch of the day, Ronan’s fever continued to rise. By the time her temperature reached 104.5° F, Ronan knew the time had come for more drastic measures.

A team of masked and gowned nurses greeted her at a triage tent outside the ED, and from there, everything becomes hazy for Ronan. She was immediately rushed to the hospital’s special COVID-19 intensive care unit (ICU), where she spent 5 days. But she has few distinct memories from this time. What she does remember is the exhaustion, the pain, the loneliness, and the fear. Her family couldn’t visit, and though Ronan works as a home health nurse, her brain was so addled with fever that she couldn’t make sense of what was happening. After a week in the hospital, 5 days of which were spent in the ICU, 51-year-old Ronan was discharged.

Her years of working as a home health nurse told her that the return home wouldn’t be easy, but nothing prepared her for just how much she would struggle. The once-active Ronan, who had supplemented long days on her feet caring for others as a nurse with regular trips to the gym, now needed a walker to traverse the few steps from her bed to the toilet, an effort that left her gasping for air. Her brain couldn’t even focus on an audiobook, let alone a short magazine article.

“It just completely knocked the stuffing out of me,” Ronan said.

Ronan’s lingering symptoms aren’t unique to COVID-19 patients. In as many as 80% of patients leaving the ICU, researchers have documented what they call post–intensive care syndrome (PICS) — a constellation of physical, cognitive, and psychiatric symptoms that result from an ICU stay. Although underlying illness plays a role in these symptoms, the amount of time spent in critical care is a major factor.

Nor is PICS simply a set of side effects that will go away on their own. It includes ongoing cognitive difficulties and physical weakness, both of which can lead to employment problems. Beyond that, depression and anxiety can exacerbate – and be exacerbated by – these challenges. Psychologist Jim Jackson, PsyD, assistant director of the ICU Recovery Center at Vanderbilt University Medical Center, Nashville, Tennessee, recently spoke with a former ICU patient who has struggled since her discharge 30 years ago.

“Her life essentially stopped with her critical care stay. She hasn’t been able to move forward,” he said. “She’s part of a whole fraternity of people who are struggling.”

The good news is that over the past decade, researchers have made important strides in understanding what makes PICS symptoms worse and how critical care physicians can tweak ICU protocols to reduce PICS severity. Practitioners will need to draw on this knowledge to help Ronan and the thousands of COVID-19 ICU patients like her.
 

Surviving the ICU

Although the new coronavirus has pushed the world’s critical care system to its limits, it was an outbreak in 1952 that inspired the creation of intensive care units. That summer, a wave of paralytic polio swept over Copenhagen, Denmark, and anesthesiologist Bjørn Ibsen, MD, PhD, used mechanical ventilation — physically operated by medical and dental students – to help 316 children breathe for weeks at a time while their small bodies worked to fight off the virus. The effort halved the mortality rate from polio that affected breathing, from 80% to 40%.

In these wards, dedicated to the very sickest, each patient was assigned his or her own nurse. Over the next decade, hospitals in the United Kingdom and the United States established their own ICUs to treat patients with a variety of conditions. Although it helped improve survival, mortality rates in critical care units remained stubbornly high, owing to the patients’ severe underlying illnesses.

“We thought we were doing a good job if the patient survived, but we had no idea what happened after discharge,” said Carla Sevin, MD, medical director of Vanderbilt’s ICU Recovery Center. Nor did their efforts to find out always bring answers. “We struggled to get people to come in for support — they were debilitated, physically burdened, and weak.”

Through further advances in life support, by the early 2000s, the average mortality rates in American ICUs had dropped to 8% to 19%. As the number of critical care survivors began to climb, clinical researchers noticed that the lives of these patients and their families were profoundly altered by their severe illness.

As Dale Needham, MD, PhD, began his pulmonology and critical care residency in Toronto, Canada, in 2005, a group of physicians there began a 5-year longitudinal study to assess long-term outcomes of patients who developed acute respiratory distress syndrome (ARDS). Although ARDS is an acute condition, the investigators found that patients felt effects for years. Younger patients recovered better than older ones, but none of the patients› physical functioning was equivalent to that of age-matched control persons. Even 5 years later, former ICU patients only reached 76% of expected physical functioning, according to results published in the New England Journal of Medicine. The study was a wake-up call.

At a meeting in Chicago in 2010, Needham, now an intensivist at Johns Hopkins Hospital in Baltimore, Maryland, gathered an interdisciplinary group of colleagues, including patients and caregivers, to clarify the phenomena they were seeing. What emerged from that meeting, published in 2012 in Critical Care Medicine, were the diagnostic criteria for PICS: According to the new definition, PICS is characterized by new or worsening physical and neuropsychiatric deficits that range from forgetfulness and loss of motivation to physical weakness and insomnia.

The issue, Needham says, is that although the trouble starts in the ICU, it only becomes clear once patients leave. “ICU doctors aren’t the ones dealing with this,” Needham said. “We need to build stronger bridges between critical care and other professions.” That’s where PICS comes in, a definition that exists explicitly to alert healthcare providers about the constellation of challenges many of these individuals face as they try to reenter “normal” life.
 

Defining the problem

As an ICU nurse at the Mayo Clinic in Rochester, Minnesota, Annie Johnson, ACNP-BC, knew lots about helping hospitalized patients, but she says she didn’t know anything about what to do after discharge – at least not until her own mother became a patient.

On the first day of retirement in October 2014, Johnson’s mother flatlined. Quick-thinking paramedics resuscitated her, and after several days in critical care, she was discharged. Since then, her heart has remained healthy. Johnson’s sister, who spent time worrying over her mother at the hospital, also had lingering effects. Both have since struggled, plagued by nightmares, flashbacks, and insomnia.

Johnson initially believed her mom’s and sister’s neuropsychiatric, post-ICU struggles were unique to her family. It was only a year later, at a seminar she was attending, that she first heard the words “post–intensive care syndrome.” Suddenly, Johnson had a name for her family’s experiences, and she began to create support groups and resources to help other families like hers.

“I thought of all the patients I had treated over the years who had been on ventilators for days and days and days. And if this happened to my mom after 48 hours, what must they be going through?” she asked.

Once physicians formally defined PICS, the Society for Critical Care Medicine helped create programs to educate ICU staff, patients, and families about potential post-discharge challenges. Researchers also began to investigate factors affecting post-ICU functioning. Follow-up studies of patients with delirium (ranging from general confusion about time and place to extreme agitation and violence) showed they had striking cognitive deficits. Problems with short-term memory, flexible thinking, and motivation plagued patients for years after their critical illness, similar to the physical deficiencies seen after ARDS. Delirium was one of the strongest risk factors for neuropsychiatric problems.

“Delirium is basically a stress test for the brain,” said Babar Khan, MD, a critical care specialist at Indiana University’s Regenstrief Institute, in Bloomington. But whether delirium accentuates preexisting cognitive difficulties or creates them afresh isn’t yet clear.

Sophia Wang, MD, a geriatric psychiatrist at Indiana University who works with many critical care patients, says patients who had experienced delirium in the ICU showed significant defects in memory and executive functioning long after their hospital stay. She points to a 2015 study that followed 47 ICU patients for a year post discharge. Among those who experienced delirium, brain volumes, as measured by MRI, were smaller at 3 months, something associated with cognitive problems at 1 year. Many struggled at work, and unemployment was common. Depression and posttraumatic stress compounded these difficulties. Among those with acute respiratory distress, ICU patients who are young, female, and unemployed are most likely to suffer from posttraumatic stress disorder after they are discharge.

Critical care medicine may have given these patients a second chance at life, Wang says, but the life they return to often looks nothing like the one they had before their illness.

Prolonged mechanical ventilation and the heavy sedation that often accompanies it are predictors of PICS severity. Some of these links could be explained by the gravity of the illness that landed someone in critical care, but others are more likely to be iatrogenic, says Gerald Weinhouse, MD, a pulmonology and critical care physician and co-director of the Critical Illness Recovery Program at the Brigham and Women’s Hospital in Boston. The involvement of loved ones at the patient’s bedside, however, improved the entire family’s outcome.

When Weinhouse saw those data, he and his colleagues founded a peer support program for ICU survivors. In a study published in 2019 in Critical Care Medicine, they identified six different models for peer support for those with PICS and their families, including both online and in-person approaches. An ongoing challenge for physicians, Weinhouse says, is getting patients to engage with these programs, given that their calendars are crowded with medical appointments and that they suffer from increased physical and mental disability.

Studies such as these led critical care physicians to form the ICU Liberation Collaborative to rethink critical care medicine. At Vanderbilt, Sevin and Jackson headed up one of the world’s first post-ICU clinics, which uses an interdisciplinary team to help patients maximize their functioning. They redesigned their critical care unit in a way that allows families to spend the night and that encourages patient mobility. Both Needham and Weinhouse continue tracking patient outcomes.

Even before the novel coronavirus struck, the United States — and the world — had begun to realize that graduating from the ICU was only the start of what was often an extensive recovery.
 

The long road back

When COVID-19 patients began flooding intensive care wards around the world, physicians scrambled to meet their complex and desperate acute medical needs. Over the past few months, physicians have focused on keeping these patients alive. “We’ve never seen anything like it ― not even during polio — with the sheer number of patients, all with respiratory distress,” Needham said.

But he and his colleagues know this is only the beginning.

“We’re aware that survivorship issues are coming. There’s going to be a wave of sick people who survived the coronavirus but are going to need more help,” Weinhouse said.

Intensivists have been drawing on PICS research in their fight to help COVID-19 patients. Work from the past few years has shown that although sedation is required during intubation itself, not everyone needs it while on a ventilator. Titrating down sedating medication helps reduce delirium, Wang says. Such medication has been shown to contribute to later cognitive problems. Needham’s studies showing that prolonged bedrest by ICU patients causes muscular atrophy has led him to encourage patients to move as much as possible. With the help of physical therapists, many patients on ventilators can be awake, alert, and moving around the ward.

One of the biggest challenges critical-care coronavirus patients face is prolonged isolation. The constant presence of a familiar face helps orient confused and delirious patients and provides emotional support during a frightening time. But because the immediate need for infection control outweighs these benefits, few hospitals allow visitors, especially for COVID-19 patients.

To address this, some units have been using video technology to allow loved ones to call in. At Johns Hopkins, physicians have also been relying on the expertise of occupational therapists (OTs). Needham says that one OT found that rubbing the hand and back of an agitated, delirious patient helped soothe and calm him better than many medications.

Ronan, who spent 5 days in intensive care, echoes that problem. She says she found the relative lack of human contact to be one of the most challenging parts of being in a bed on a COVID-19 ward. Separated from her husband and daughter, suffering from high fever and severe illness, she lost all track of time.

Her return home was difficult, too. Although her job as a home health nurse had prepared her on some level for the challenges she would face after discharge, Ronan says the hospital provided little practical help.

“Everything is so much harder at home, even little things like going to the bathroom,” she said. “I feel like I’m trying to bail out a sinking ship with a teacup.”

Khan and other physicians, aware of the challenges Ronan and others face once home, aim to create post-ICU clinics specifically for COVID-19 patients. They want to build what Khan calls a “one-stop shop” for all the support patients need to recover. Some of that can be provided via telehealth, which may also help ease the physical burden.

Because there’s so much physicians don’t know about the coronavirus, Johnson says, such clinics are not only a chance to help the sickest COVID-19 patients, they will also help researchers learn more about the virus and improve critical care for other illnesses.

Today, nearly 2 months after discharge, Ronan is back on the job but struggles with a persistent cough — likely due to the lung damage she sustained while ill. She has constant fatigue, as well as ongoing upset stomach from all the medications she took to reduce fever and body aches. When she dons a mask for work, the tangible reminder of her hospital stay sends her into a panic attack. Physically, she’s weaker than before.

Researchers are still trying to understand everything that Ronan and other COVID-19 patients need to move on with their lives after being in the ICU. Mysteries abound, but the ground laid by Sevin, Needham, Weinhouse, and others has provided a solid foundation on which to build.
 

This article first appeared on Medscape.com.

Cardiovascular risk continues to reduce as systolic blood pressure decreases right down to levels as low as 90 mm Hg, a new study has shown.

The study analyzed data from a cohort of 1,457 participants (mean age, 58 years) who did not have any traditional cardiovascular risk factors and had a systolic blood pressure level between 90 and 129 mm Hg at baseline. Results showed that, during a mean follow-up of 14.5 years, there was an increase in traditional cardiovascular risk factors, coronary artery calcium, and incident cardiovascular events with increasing systolic blood pressure levels.

“We modeled systolic blood pressure on a continuous scale and saw the risk increasing in a linear fashion as blood pressure increased and this occurred right down to 90 mm Hg. We didn’t see any nadir or J-point where there may be an increased risk at lower pressures,” said lead author Seamus Whelton, MD.

Dr. Whelton is assistant professor of medicine at the division of cardiology at Johns Hopkins Medicine, Baltimore. He is the son of Paul Whelton, MD, chair of the 2017 American College of Cardiology/American Heart Association hypertension guideline writing committee.

“From an individual level we can now say that in healthy individuals, a systolic pressure in the 90s is not too low. It is a positive thing. And it is recommended to try and keep systolic pressure at these levels if possible by maintaining a healthy lifestyle,” Dr. Whelton said in an interview. “At a population level this finding could lead to stronger recommendations on interventions to prevent increasing blood pressure such as healthier diets, reducing sodium intake, and increasing exercise. Small changes in blood pressure on a population level will lead to large changes in cardiovascular risk on a population a level.”

The study was published online in JAMA Cardiology on June 10.

The researchers noted that populations in nonindustrialized countries have little to no increase in systolic blood pressure levels with age, while systolic blood pressure levels typically increase with age in countries with industrialized diets and lifestyles. This has important implications, because atherosclerosis is a slowly progressive disease and the lower an individual’s lifetime exposure to cardiovascular risk factors, such as increased systolic blood pressure, the lower their probable risk for a future cardiovascular event, they wrote.

While the association between systolic blood pressure level, coronary artery calcium, and atherosclerotic cardiovascular disease is well established at higher blood pressure levels, optimal systolic pressure levels for a healthy adult and whether there is a J-shaped relationship or lower limit of systolic pressure necessary to maintain adequate organ perfusion has been uncertain, they explained.

In addition, prior studies have typically used a reference systolic pressure of less than 115-120 mm Hg to define a normal level, and it is uncertain whether there is a lower level at which the risk for incident cardiovascular disease plateaus or increases.

To investigate this, they analyzed data from the Multi-Ethnic Study of Atherosclerosis, a community-based, multiethnic cohort free from known cardiovascular disease at enrollment. The current analysis included individuals with a systolic blood pressure between 90 and 129 mm Hg without other traditional cardiovascular risk factors including dyslipidemia (LDL cholesterol >160 mg/dL or HDL cholesterol <40 mg/dL), diabetes, or current tobacco use.

Results showed an adjusted hazard ratio for atherosclerotic cardiovascular disease was 1.53 for every 10 mm Hg increase in systolic blood pressure levels.

Compared with people with systolic pressures of 90-99 mm Hg, the adjusted hazard ratio for atherosclerotic cardiovascular disease risk was 3.00 for those with 100-109 mm Hg, 3.10 for those with 110-119 mm Hg, and 4.58 for those with 120-129 mm Hg.

There was also a graded increase in the prevalence of coronary artery calcium starting from systolic blood pressure levels as low as 90 mm Hg.

“Previous research on the J-shaped curve for blood pressure has primarily focused on diastolic pressure. We did control for diastolic pressure in this analysis but that was not the focus,” Dr. Whelton said. “Obviously, there will be a minimum optimum value for both diastolic and systolic pressure. But from this study we can say that for systolic pressure, that minimum recommended value is below 90 mm Hg.”

In terms of implications, the researchers wrote: “Among individuals at low or intermediate atherosclerotic cardiovascular risk, it may be more efficacious to focus on a life-course approach for preventing an increase in systolic blood pressure levels rather than treatment of established hypertension to lower systolic blood pressure levels.”

What is a normal blood pressure?

In an accompanying commentary, Daniel Jones, MD, of the University of Mississippi Medical Center, Jackson, said these new findings support the position that risk imposed by blood pressure level begins well below the current 130/80 mm Hg definition of hypertension and guideline-recommended goal.

The study is “a reminder that even a good execution of treatment of hypertension is far from an ideal way to prevent atherosclerotic cardiovascular disease,” he said.

“A systolic of 130 is not the number we should focus on for patients who are not yet hypertensive, as 130 is not a normal blood pressure,” Dr. Jones added in an audio interview on the JAMA website.

“The findings also suggest that the disease process for atherosclerotic cardiovascular disease begins early in life and support the importance of primordial prevention through a healthy lifestyle, including a healthy diet and levels of physical activity. In addition, the findings highlight the need for a population-based strategy focusing on primordial prevention to reduce the age-related increase in BP reported in all industrialized societies,” Dr. Jones wrote.

He recommended that clinicians encourage a healthy lifestyle in patients and families of patients with cardiovascular disease. “This intervention requires no sophisticated genetic testing or clinical trials to credibly inform a family that the children and grandchildren of a patient with atherosclerotic cardiovascular disease or risk factors will benefit from a healthy lifestyle beginning at the earliest age.

“Clinicians often lose sight of the big picture with regard to blood pressure because they have the patient in front of them. But that patient has children and grandchildren who may share the risk and may be in a better position with regard to prevention of future [coronary artery disease], stroke, and kidney disease,” he said.

Conducting the JAMA audio interview, Clyde Yancy, MD, chief of cardiology at Northwestern University, Chicago, said that “this is very stimulating research. It is not asking the question of what is the target blood pressure for patients with hypertension, but rather: What is the goal blood pressure if you actually want to avoid atherosclerotic cardiovascular disease risk altogether?

“These data have made us understand that there is a difference between the goal blood pressure reduction and treatment thresholds that we respect, the normative blood pressure values we see in a clinical setting, and what is truly normal blood pressure,” Dr. Yancy concluded. “That is a very important nuance, especially when we’re talking about population health. Families and communities need to understand what the true normal is.”

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

Cardiovascular risk continues to reduce as systolic blood pressure decreases right down to levels as low as 90 mm Hg, a new study has shown.

The study analyzed data from a cohort of 1,457 participants (mean age, 58 years) who did not have any traditional cardiovascular risk factors and had a systolic blood pressure level between 90 and 129 mm Hg at baseline. Results showed that, during a mean follow-up of 14.5 years, there was an increase in traditional cardiovascular risk factors, coronary artery calcium, and incident cardiovascular events with increasing systolic blood pressure levels.

“We modeled systolic blood pressure on a continuous scale and saw the risk increasing in a linear fashion as blood pressure increased and this occurred right down to 90 mm Hg. We didn’t see any nadir or J-point where there may be an increased risk at lower pressures,” said lead author Seamus Whelton, MD.

Dr. Whelton is assistant professor of medicine at the division of cardiology at Johns Hopkins Medicine, Baltimore. He is the son of Paul Whelton, MD, chair of the 2017 American College of Cardiology/American Heart Association hypertension guideline writing committee.

“From an individual level we can now say that in healthy individuals, a systolic pressure in the 90s is not too low. It is a positive thing. And it is recommended to try and keep systolic pressure at these levels if possible by maintaining a healthy lifestyle,” Dr. Whelton said in an interview. “At a population level this finding could lead to stronger recommendations on interventions to prevent increasing blood pressure such as healthier diets, reducing sodium intake, and increasing exercise. Small changes in blood pressure on a population level will lead to large changes in cardiovascular risk on a population a level.”

The study was published online in JAMA Cardiology on June 10.

The researchers noted that populations in nonindustrialized countries have little to no increase in systolic blood pressure levels with age, while systolic blood pressure levels typically increase with age in countries with industrialized diets and lifestyles. This has important implications, because atherosclerosis is a slowly progressive disease and the lower an individual’s lifetime exposure to cardiovascular risk factors, such as increased systolic blood pressure, the lower their probable risk for a future cardiovascular event, they wrote.

While the association between systolic blood pressure level, coronary artery calcium, and atherosclerotic cardiovascular disease is well established at higher blood pressure levels, optimal systolic pressure levels for a healthy adult and whether there is a J-shaped relationship or lower limit of systolic pressure necessary to maintain adequate organ perfusion has been uncertain, they explained.

In addition, prior studies have typically used a reference systolic pressure of less than 115-120 mm Hg to define a normal level, and it is uncertain whether there is a lower level at which the risk for incident cardiovascular disease plateaus or increases.

To investigate this, they analyzed data from the Multi-Ethnic Study of Atherosclerosis, a community-based, multiethnic cohort free from known cardiovascular disease at enrollment. The current analysis included individuals with a systolic blood pressure between 90 and 129 mm Hg without other traditional cardiovascular risk factors including dyslipidemia (LDL cholesterol >160 mg/dL or HDL cholesterol <40 mg/dL), diabetes, or current tobacco use.

Results showed an adjusted hazard ratio for atherosclerotic cardiovascular disease was 1.53 for every 10 mm Hg increase in systolic blood pressure levels.

Compared with people with systolic pressures of 90-99 mm Hg, the adjusted hazard ratio for atherosclerotic cardiovascular disease risk was 3.00 for those with 100-109 mm Hg, 3.10 for those with 110-119 mm Hg, and 4.58 for those with 120-129 mm Hg.

There was also a graded increase in the prevalence of coronary artery calcium starting from systolic blood pressure levels as low as 90 mm Hg.

“Previous research on the J-shaped curve for blood pressure has primarily focused on diastolic pressure. We did control for diastolic pressure in this analysis but that was not the focus,” Dr. Whelton said. “Obviously, there will be a minimum optimum value for both diastolic and systolic pressure. But from this study we can say that for systolic pressure, that minimum recommended value is below 90 mm Hg.”

In terms of implications, the researchers wrote: “Among individuals at low or intermediate atherosclerotic cardiovascular risk, it may be more efficacious to focus on a life-course approach for preventing an increase in systolic blood pressure levels rather than treatment of established hypertension to lower systolic blood pressure levels.”

What is a normal blood pressure?

In an accompanying commentary, Daniel Jones, MD, of the University of Mississippi Medical Center, Jackson, said these new findings support the position that risk imposed by blood pressure level begins well below the current 130/80 mm Hg definition of hypertension and guideline-recommended goal.

The study is “a reminder that even a good execution of treatment of hypertension is far from an ideal way to prevent atherosclerotic cardiovascular disease,” he said.

“A systolic of 130 is not the number we should focus on for patients who are not yet hypertensive, as 130 is not a normal blood pressure,” Dr. Jones added in an audio interview on the JAMA website.

“The findings also suggest that the disease process for atherosclerotic cardiovascular disease begins early in life and support the importance of primordial prevention through a healthy lifestyle, including a healthy diet and levels of physical activity. In addition, the findings highlight the need for a population-based strategy focusing on primordial prevention to reduce the age-related increase in BP reported in all industrialized societies,” Dr. Jones wrote.

He recommended that clinicians encourage a healthy lifestyle in patients and families of patients with cardiovascular disease. “This intervention requires no sophisticated genetic testing or clinical trials to credibly inform a family that the children and grandchildren of a patient with atherosclerotic cardiovascular disease or risk factors will benefit from a healthy lifestyle beginning at the earliest age.

“Clinicians often lose sight of the big picture with regard to blood pressure because they have the patient in front of them. But that patient has children and grandchildren who may share the risk and may be in a better position with regard to prevention of future [coronary artery disease], stroke, and kidney disease,” he said.

Conducting the JAMA audio interview, Clyde Yancy, MD, chief of cardiology at Northwestern University, Chicago, said that “this is very stimulating research. It is not asking the question of what is the target blood pressure for patients with hypertension, but rather: What is the goal blood pressure if you actually want to avoid atherosclerotic cardiovascular disease risk altogether?

“These data have made us understand that there is a difference between the goal blood pressure reduction and treatment thresholds that we respect, the normative blood pressure values we see in a clinical setting, and what is truly normal blood pressure,” Dr. Yancy concluded. “That is a very important nuance, especially when we’re talking about population health. Families and communities need to understand what the true normal is.”

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

Cardiovascular risk continues to reduce as systolic blood pressure decreases right down to levels as low as 90 mm Hg, a new study has shown.

The study analyzed data from a cohort of 1,457 participants (mean age, 58 years) who did not have any traditional cardiovascular risk factors and had a systolic blood pressure level between 90 and 129 mm Hg at baseline. Results showed that, during a mean follow-up of 14.5 years, there was an increase in traditional cardiovascular risk factors, coronary artery calcium, and incident cardiovascular events with increasing systolic blood pressure levels.

“We modeled systolic blood pressure on a continuous scale and saw the risk increasing in a linear fashion as blood pressure increased and this occurred right down to 90 mm Hg. We didn’t see any nadir or J-point where there may be an increased risk at lower pressures,” said lead author Seamus Whelton, MD.

Dr. Whelton is assistant professor of medicine at the division of cardiology at Johns Hopkins Medicine, Baltimore. He is the son of Paul Whelton, MD, chair of the 2017 American College of Cardiology/American Heart Association hypertension guideline writing committee.

“From an individual level we can now say that in healthy individuals, a systolic pressure in the 90s is not too low. It is a positive thing. And it is recommended to try and keep systolic pressure at these levels if possible by maintaining a healthy lifestyle,” Dr. Whelton said in an interview. “At a population level this finding could lead to stronger recommendations on interventions to prevent increasing blood pressure such as healthier diets, reducing sodium intake, and increasing exercise. Small changes in blood pressure on a population level will lead to large changes in cardiovascular risk on a population a level.”

The study was published online in JAMA Cardiology on June 10.

The researchers noted that populations in nonindustrialized countries have little to no increase in systolic blood pressure levels with age, while systolic blood pressure levels typically increase with age in countries with industrialized diets and lifestyles. This has important implications, because atherosclerosis is a slowly progressive disease and the lower an individual’s lifetime exposure to cardiovascular risk factors, such as increased systolic blood pressure, the lower their probable risk for a future cardiovascular event, they wrote.

While the association between systolic blood pressure level, coronary artery calcium, and atherosclerotic cardiovascular disease is well established at higher blood pressure levels, optimal systolic pressure levels for a healthy adult and whether there is a J-shaped relationship or lower limit of systolic pressure necessary to maintain adequate organ perfusion has been uncertain, they explained.

In addition, prior studies have typically used a reference systolic pressure of less than 115-120 mm Hg to define a normal level, and it is uncertain whether there is a lower level at which the risk for incident cardiovascular disease plateaus or increases.

To investigate this, they analyzed data from the Multi-Ethnic Study of Atherosclerosis, a community-based, multiethnic cohort free from known cardiovascular disease at enrollment. The current analysis included individuals with a systolic blood pressure between 90 and 129 mm Hg without other traditional cardiovascular risk factors including dyslipidemia (LDL cholesterol >160 mg/dL or HDL cholesterol <40 mg/dL), diabetes, or current tobacco use.

Results showed an adjusted hazard ratio for atherosclerotic cardiovascular disease was 1.53 for every 10 mm Hg increase in systolic blood pressure levels.

Compared with people with systolic pressures of 90-99 mm Hg, the adjusted hazard ratio for atherosclerotic cardiovascular disease risk was 3.00 for those with 100-109 mm Hg, 3.10 for those with 110-119 mm Hg, and 4.58 for those with 120-129 mm Hg.

There was also a graded increase in the prevalence of coronary artery calcium starting from systolic blood pressure levels as low as 90 mm Hg.

“Previous research on the J-shaped curve for blood pressure has primarily focused on diastolic pressure. We did control for diastolic pressure in this analysis but that was not the focus,” Dr. Whelton said. “Obviously, there will be a minimum optimum value for both diastolic and systolic pressure. But from this study we can say that for systolic pressure, that minimum recommended value is below 90 mm Hg.”

In terms of implications, the researchers wrote: “Among individuals at low or intermediate atherosclerotic cardiovascular risk, it may be more efficacious to focus on a life-course approach for preventing an increase in systolic blood pressure levels rather than treatment of established hypertension to lower systolic blood pressure levels.”

What is a normal blood pressure?

In an accompanying commentary, Daniel Jones, MD, of the University of Mississippi Medical Center, Jackson, said these new findings support the position that risk imposed by blood pressure level begins well below the current 130/80 mm Hg definition of hypertension and guideline-recommended goal.

The study is “a reminder that even a good execution of treatment of hypertension is far from an ideal way to prevent atherosclerotic cardiovascular disease,” he said.

“A systolic of 130 is not the number we should focus on for patients who are not yet hypertensive, as 130 is not a normal blood pressure,” Dr. Jones added in an audio interview on the JAMA website.

“The findings also suggest that the disease process for atherosclerotic cardiovascular disease begins early in life and support the importance of primordial prevention through a healthy lifestyle, including a healthy diet and levels of physical activity. In addition, the findings highlight the need for a population-based strategy focusing on primordial prevention to reduce the age-related increase in BP reported in all industrialized societies,” Dr. Jones wrote.

He recommended that clinicians encourage a healthy lifestyle in patients and families of patients with cardiovascular disease. “This intervention requires no sophisticated genetic testing or clinical trials to credibly inform a family that the children and grandchildren of a patient with atherosclerotic cardiovascular disease or risk factors will benefit from a healthy lifestyle beginning at the earliest age.

“Clinicians often lose sight of the big picture with regard to blood pressure because they have the patient in front of them. But that patient has children and grandchildren who may share the risk and may be in a better position with regard to prevention of future [coronary artery disease], stroke, and kidney disease,” he said.

Conducting the JAMA audio interview, Clyde Yancy, MD, chief of cardiology at Northwestern University, Chicago, said that “this is very stimulating research. It is not asking the question of what is the target blood pressure for patients with hypertension, but rather: What is the goal blood pressure if you actually want to avoid atherosclerotic cardiovascular disease risk altogether?

“These data have made us understand that there is a difference between the goal blood pressure reduction and treatment thresholds that we respect, the normative blood pressure values we see in a clinical setting, and what is truly normal blood pressure,” Dr. Yancy concluded. “That is a very important nuance, especially when we’re talking about population health. Families and communities need to understand what the true normal is.”

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

Young men with hidradenitis suppurativa are “surprisingly” at increased risk for hypothyroidism, Anna Figueiredo, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

The surprise about this finding from a large retrospective case-control study stems from the fact that the elevated risk for hypothyroidism didn’t also extend to younger women with hidradenitis suppurativa (HS) nor to patients older than 40 years of either gender, explained Dr. Figueiredo of the department of dermatology at Northwestern University, Chicago.

She presented a retrospective case-control study based on information extracted from a medical records database of more than 8 million Midwestern adults. Among nearly 141,000 dermatology patients with follow-up in the database for at least 1 year, there were 405 HS patients aged 18-40 years and 327 aged 41-89.

In an age-matched comparison with the dermatology patients without HS, the younger HS cohort was at a significant 1.52-fold increased risk for comorbid hypothyroidism. Upon further stratification by sex, only the younger men with HS were at increased risk. Those patients were at 3.95-fold greater risk for having a diagnosis of hypothyroidism than were age-matched younger male dermatology patients.

Both younger and older HS patients were at numerically increased risk for being diagnosed with hyperthyroidism; however, this difference didn’t approach statistical significance because there were so few cases: a total of just eight in the HS population across the full age spectrum.

Hidradenitis suppurativa is a chronic inflammatory disease with an estimated prevalence of up to 4% in the United States. Growing evidence suggests it is an immune-mediated disorder because the tumor necrosis factor inhibitor adalimumab (Humira) has been approved for treatment of HS.

Thyroid disease is also often autoimmune-mediated, but its relationship with HS hasn’t been extensively examined. A recent meta-analysis of five case-control studies concluded that HS was associated with a 1.36-fold increased risk of thyroid disease; however, the Nepalese investigators didn’t distinguish between hypo- and hyperthyroidism (J Am Acad Dermatol. 2020 Feb;82[2]:491-3).

Dr. Figueiredo reported having no financial conflicts regarding her study, which was without commercial support.

bjancin@mdedge.com

Young men with hidradenitis suppurativa are “surprisingly” at increased risk for hypothyroidism, Anna Figueiredo, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

The surprise about this finding from a large retrospective case-control study stems from the fact that the elevated risk for hypothyroidism didn’t also extend to younger women with hidradenitis suppurativa (HS) nor to patients older than 40 years of either gender, explained Dr. Figueiredo of the department of dermatology at Northwestern University, Chicago.

She presented a retrospective case-control study based on information extracted from a medical records database of more than 8 million Midwestern adults. Among nearly 141,000 dermatology patients with follow-up in the database for at least 1 year, there were 405 HS patients aged 18-40 years and 327 aged 41-89.

In an age-matched comparison with the dermatology patients without HS, the younger HS cohort was at a significant 1.52-fold increased risk for comorbid hypothyroidism. Upon further stratification by sex, only the younger men with HS were at increased risk. Those patients were at 3.95-fold greater risk for having a diagnosis of hypothyroidism than were age-matched younger male dermatology patients.

Both younger and older HS patients were at numerically increased risk for being diagnosed with hyperthyroidism; however, this difference didn’t approach statistical significance because there were so few cases: a total of just eight in the HS population across the full age spectrum.

Hidradenitis suppurativa is a chronic inflammatory disease with an estimated prevalence of up to 4% in the United States. Growing evidence suggests it is an immune-mediated disorder because the tumor necrosis factor inhibitor adalimumab (Humira) has been approved for treatment of HS.

Thyroid disease is also often autoimmune-mediated, but its relationship with HS hasn’t been extensively examined. A recent meta-analysis of five case-control studies concluded that HS was associated with a 1.36-fold increased risk of thyroid disease; however, the Nepalese investigators didn’t distinguish between hypo- and hyperthyroidism (J Am Acad Dermatol. 2020 Feb;82[2]:491-3).

Dr. Figueiredo reported having no financial conflicts regarding her study, which was without commercial support.

bjancin@mdedge.com

Young men with hidradenitis suppurativa are “surprisingly” at increased risk for hypothyroidism, Anna Figueiredo, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

The surprise about this finding from a large retrospective case-control study stems from the fact that the elevated risk for hypothyroidism didn’t also extend to younger women with hidradenitis suppurativa (HS) nor to patients older than 40 years of either gender, explained Dr. Figueiredo of the department of dermatology at Northwestern University, Chicago.

She presented a retrospective case-control study based on information extracted from a medical records database of more than 8 million Midwestern adults. Among nearly 141,000 dermatology patients with follow-up in the database for at least 1 year, there were 405 HS patients aged 18-40 years and 327 aged 41-89.

In an age-matched comparison with the dermatology patients without HS, the younger HS cohort was at a significant 1.52-fold increased risk for comorbid hypothyroidism. Upon further stratification by sex, only the younger men with HS were at increased risk. Those patients were at 3.95-fold greater risk for having a diagnosis of hypothyroidism than were age-matched younger male dermatology patients.

Both younger and older HS patients were at numerically increased risk for being diagnosed with hyperthyroidism; however, this difference didn’t approach statistical significance because there were so few cases: a total of just eight in the HS population across the full age spectrum.

Hidradenitis suppurativa is a chronic inflammatory disease with an estimated prevalence of up to 4% in the United States. Growing evidence suggests it is an immune-mediated disorder because the tumor necrosis factor inhibitor adalimumab (Humira) has been approved for treatment of HS.

Thyroid disease is also often autoimmune-mediated, but its relationship with HS hasn’t been extensively examined. A recent meta-analysis of five case-control studies concluded that HS was associated with a 1.36-fold increased risk of thyroid disease; however, the Nepalese investigators didn’t distinguish between hypo- and hyperthyroidism (J Am Acad Dermatol. 2020 Feb;82[2]:491-3).

Dr. Figueiredo reported having no financial conflicts regarding her study, which was without commercial support.

bjancin@mdedge.com

The challenges posed by COVID-19 have crippled health care systems around the globe. By February 2020, the first outbreak in the United States had been set off in Washington State. We quickly became the world’s epicenter of the epidemic, with over 1.8 million patients and over 110,000 deaths.¹ The rapidity of spread and the severity of the disease created a tremendous strain on resources. It blindsided policymakers and hospital administrators, which left little time to react to the challenges placed on hospital operations all over the country.

The necessity of a new care model

Although health systems in the United States are adept in managing complications of common seasonal viral respiratory illnesses, COVID-19 presented an entirely different challenge with its significantly higher mortality rate. A respiratory disease turning into a multiorgan disease that causes debilitating cardiac, renal, neurological, hematological, and psychosocial complications² was not something we had experience managing effectively. Additional challenges included a massive surge of COVID-19 patients, a limited supply of personal protective equipment (PPE), an inadequate number of intensivists for managing the anticipated ventilated patients, and most importantly, the potential of losing some of our workforce if they became infected.

Based on the experiences in China and Italy, and various predictive models, the division of hospital medicine at Baystate Health quickly realized the necessity of a new model of care for COVID-19 patients. We came up with an elaborate plan to manage the disease burden and the strain on resources effectively. The measures we put in place could be broadly divided into three categories following the timeline of the disease: the preparatory phase, the execution phase, and the maintenance phase.
 

The preparatory phase: From “Hospitalists” to “COVIDists”

As in most hospitals around the country, hospitalists are the backbone of inpatient clinical operations at our health system. A focused group of 10 hospitalists who volunteered to take care of COVID-19 patients with a particular interest in the pandemic and experience in critical care were selected, and the term “COVIDists” was coined to refer to them.

COVIDists were trained in various treatment protocols and ongoing clinical trials. They were given refresher training in Advanced Cardiac Life Support (ACLS) and Fundamental Critical Care Support (FCCS) courses and were taught in critical care/ventilator management by the intensivists through rapid indoctrination in the ICU. All of them had their N-95 mask fitting updated and were trained in the safe donning and doffing of all kinds of PPE by PPE coaches. The palliative care team trained them in conducting end-of-life/code status discussions with a focus on being unable to speak with family members at the bedside. COVIDists were also assigned as Code Blue leaders for any “COVID code blue” in the hospital.

In addition to the rapid training course, COVID-related updates were disseminated daily using three different modalities: brief huddles at the start of the day with the COVIDists; a COVID-19 newsletter summarizing daily updates, new treatments, strategies, and policies; and a WhatsApp group for instantly broadcasting information to the COVIDists (Table 1).

The execution phase

All the hospitalized COVID-19 patients were grouped together to COVID units, and the COVIDists were deployed to those units geographically. COVIDists were given lighter than usual patient loads to deal with the extra time needed for donning and doffing of PPE and for coordination with specialists. COVIDists were almost the only clinicians physically visiting the patients in most cases, and they became the “eyes and ears” of specialists since the specialists were advised to minimize exposure and pursue telemedicine consults. The COVIDists were also undertaking the most challenging part of the care – talking to families about end-of-life issues and the futility of aggressive care in certain patients with preexisting conditions.

Some COVIDists were deployed to the ICU to work alongside the intensivists and became an invaluable resource in ICU management when the ICU census skyrocketed during the initial phase of the outbreak. This helped in tiding the health system over during the initial crisis. Within a short time, we shifted away from an early intubation strategy, and most of the ICU patients were managed in the intermediate care units on high flow oxygen along with the awake-proning protocol. The COVIDists exclusively managed these units. They led multidisciplinary rounds two times a day with the ICU, rapid response team (RRT), the palliative care team, and the nursing team. This step drastically decreased the number of intubations, RRT activations, reduced ICU census,³ and helped with hospital capacity and patient flow (Tables 2 and 3).

The maintenance phase

It is already 2 months since the first devising COVIDists. There is no difference in sick callouts between COVIDists and non-COVIDists. One COVIDist and one non-COVIDist contracted the disease, but none of them required hospitalization. Although we initially thought that COVIDists would be needed for only a short period of time, the evolution of the disease is showing signs that it might be prolonged over the next several months. Hence, we are planning to continue COVIDist service for at least the next 6 months and reevaluate the need.

Hospital medicine leadership checked on COVIDists daily in regard to their physical health and, more importantly, their mental well-being. They were offered the chance to be taken off the schedule if they felt burned out, but no one wanted to come off their scheduled service before finishing their shifts. BlueCross MA recognized one of the COVIDists, Raghuveer Rakasi, MD, as a “hero on the front line.”⁴ In Dr. Rakasi’s words, “We took a nosedive into something without knowing its depth, and aware that we could have fatalities among ourselves. We took up new roles, faced new challenges, learned new things every day, evolving every step of the way. We had to change the way we practice medicine, finding new ways to treat patients, and protecting the workforce by limiting patient exposure, prioritizing investigations.” He added that “we have to adapt to a new normal; we should be prepared for this to come in waves. Putting aside our political views, we should stand united 6 feet apart, with a mask covering our brave faces, frequently washing our helping hands to overcome these uncertain times.”
 

Conclusion

The creation of a focused group of hospitalists called COVIDists and providing them with structured and rapid training (in various aspects of clinical care of COVID-19 patients, critical care/ventilator management, efficient and safe use of PPE) and daily information dissemination allowed our health system to prepare for the large volume of COVID-19 patients. It also helped in preserving the larger hospital workforce for a possible future surge.

The rapid development and implementation of the COVIDist strategy succeeded because of the intrinsic motivation of the providers to improve the outcomes of this high-risk patient population and the close collaboration of the stakeholders. Our institution remains successful in managing the pandemic in Western Massachusetts, with reserve capacity remaining even during the peak of the epidemic. A large part of this was because of creating and training a pool of COVIDists.
 

Dr. Medarametla is medical director, clinical operations, in the division of hospital medicine at Baystate Health, and assistant professor at University of Massachusetts, Worcester. Readers can contact him at Venkatrao.MedarametlaMD@Baystatehealth.org. Dr. Prabhakaran is unit medical director, geriatrics unit, in the division of hospital medicine at Baystate Health and assistant professor at University of Massachusetts. Dr. Bryson is associate program director of the Internal Medicine Residency at Baystate Health and assistant professor at University of Massachusetts. Dr. Umar is medical director, clinical operations, in the division of hospital medicine at Baystate Health. Dr. Natanasabapathy is division chief of hospital medicine at Baystate Health and assistant professor at University of Massachusetts.

References

1. Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19). Updated Jun 10, 2020. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html.

2. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.

3. Westafer LM et al. A transdisciplinary COVID-19 early respiratory intervention protocol: An implementation story. J Hosp Med. 2020 May 21;15(6):372-374.

4. Miller J. “Heroes on the front line: Dr. Raghuveer Rakasi.” Coverage. May 18, 2020. https://coverage.bluecrossma.com/article/heroes-front-line-dr-raghuveer-rakasi

The challenges posed by COVID-19 have crippled health care systems around the globe. By February 2020, the first outbreak in the United States had been set off in Washington State. We quickly became the world’s epicenter of the epidemic, with over 1.8 million patients and over 110,000 deaths.¹ The rapidity of spread and the severity of the disease created a tremendous strain on resources. It blindsided policymakers and hospital administrators, which left little time to react to the challenges placed on hospital operations all over the country.

The necessity of a new care model

Although health systems in the United States are adept in managing complications of common seasonal viral respiratory illnesses, COVID-19 presented an entirely different challenge with its significantly higher mortality rate. A respiratory disease turning into a multiorgan disease that causes debilitating cardiac, renal, neurological, hematological, and psychosocial complications² was not something we had experience managing effectively. Additional challenges included a massive surge of COVID-19 patients, a limited supply of personal protective equipment (PPE), an inadequate number of intensivists for managing the anticipated ventilated patients, and most importantly, the potential of losing some of our workforce if they became infected.

Based on the experiences in China and Italy, and various predictive models, the division of hospital medicine at Baystate Health quickly realized the necessity of a new model of care for COVID-19 patients. We came up with an elaborate plan to manage the disease burden and the strain on resources effectively. The measures we put in place could be broadly divided into three categories following the timeline of the disease: the preparatory phase, the execution phase, and the maintenance phase.
 

The preparatory phase: From “Hospitalists” to “COVIDists”

As in most hospitals around the country, hospitalists are the backbone of inpatient clinical operations at our health system. A focused group of 10 hospitalists who volunteered to take care of COVID-19 patients with a particular interest in the pandemic and experience in critical care were selected, and the term “COVIDists” was coined to refer to them.

COVIDists were trained in various treatment protocols and ongoing clinical trials. They were given refresher training in Advanced Cardiac Life Support (ACLS) and Fundamental Critical Care Support (FCCS) courses and were taught in critical care/ventilator management by the intensivists through rapid indoctrination in the ICU. All of them had their N-95 mask fitting updated and were trained in the safe donning and doffing of all kinds of PPE by PPE coaches. The palliative care team trained them in conducting end-of-life/code status discussions with a focus on being unable to speak with family members at the bedside. COVIDists were also assigned as Code Blue leaders for any “COVID code blue” in the hospital.

In addition to the rapid training course, COVID-related updates were disseminated daily using three different modalities: brief huddles at the start of the day with the COVIDists; a COVID-19 newsletter summarizing daily updates, new treatments, strategies, and policies; and a WhatsApp group for instantly broadcasting information to the COVIDists (Table 1).

The execution phase

All the hospitalized COVID-19 patients were grouped together to COVID units, and the COVIDists were deployed to those units geographically. COVIDists were given lighter than usual patient loads to deal with the extra time needed for donning and doffing of PPE and for coordination with specialists. COVIDists were almost the only clinicians physically visiting the patients in most cases, and they became the “eyes and ears” of specialists since the specialists were advised to minimize exposure and pursue telemedicine consults. The COVIDists were also undertaking the most challenging part of the care – talking to families about end-of-life issues and the futility of aggressive care in certain patients with preexisting conditions.

Some COVIDists were deployed to the ICU to work alongside the intensivists and became an invaluable resource in ICU management when the ICU census skyrocketed during the initial phase of the outbreak. This helped in tiding the health system over during the initial crisis. Within a short time, we shifted away from an early intubation strategy, and most of the ICU patients were managed in the intermediate care units on high flow oxygen along with the awake-proning protocol. The COVIDists exclusively managed these units. They led multidisciplinary rounds two times a day with the ICU, rapid response team (RRT), the palliative care team, and the nursing team. This step drastically decreased the number of intubations, RRT activations, reduced ICU census,³ and helped with hospital capacity and patient flow (Tables 2 and 3).

The maintenance phase

It is already 2 months since the first devising COVIDists. There is no difference in sick callouts between COVIDists and non-COVIDists. One COVIDist and one non-COVIDist contracted the disease, but none of them required hospitalization. Although we initially thought that COVIDists would be needed for only a short period of time, the evolution of the disease is showing signs that it might be prolonged over the next several months. Hence, we are planning to continue COVIDist service for at least the next 6 months and reevaluate the need.

Hospital medicine leadership checked on COVIDists daily in regard to their physical health and, more importantly, their mental well-being. They were offered the chance to be taken off the schedule if they felt burned out, but no one wanted to come off their scheduled service before finishing their shifts. BlueCross MA recognized one of the COVIDists, Raghuveer Rakasi, MD, as a “hero on the front line.”⁴ In Dr. Rakasi’s words, “We took a nosedive into something without knowing its depth, and aware that we could have fatalities among ourselves. We took up new roles, faced new challenges, learned new things every day, evolving every step of the way. We had to change the way we practice medicine, finding new ways to treat patients, and protecting the workforce by limiting patient exposure, prioritizing investigations.” He added that “we have to adapt to a new normal; we should be prepared for this to come in waves. Putting aside our political views, we should stand united 6 feet apart, with a mask covering our brave faces, frequently washing our helping hands to overcome these uncertain times.”
 

Conclusion

The creation of a focused group of hospitalists called COVIDists and providing them with structured and rapid training (in various aspects of clinical care of COVID-19 patients, critical care/ventilator management, efficient and safe use of PPE) and daily information dissemination allowed our health system to prepare for the large volume of COVID-19 patients. It also helped in preserving the larger hospital workforce for a possible future surge.

The rapid development and implementation of the COVIDist strategy succeeded because of the intrinsic motivation of the providers to improve the outcomes of this high-risk patient population and the close collaboration of the stakeholders. Our institution remains successful in managing the pandemic in Western Massachusetts, with reserve capacity remaining even during the peak of the epidemic. A large part of this was because of creating and training a pool of COVIDists.
 

Dr. Medarametla is medical director, clinical operations, in the division of hospital medicine at Baystate Health, and assistant professor at University of Massachusetts, Worcester. Readers can contact him at Venkatrao.MedarametlaMD@Baystatehealth.org. Dr. Prabhakaran is unit medical director, geriatrics unit, in the division of hospital medicine at Baystate Health and assistant professor at University of Massachusetts. Dr. Bryson is associate program director of the Internal Medicine Residency at Baystate Health and assistant professor at University of Massachusetts. Dr. Umar is medical director, clinical operations, in the division of hospital medicine at Baystate Health. Dr. Natanasabapathy is division chief of hospital medicine at Baystate Health and assistant professor at University of Massachusetts.

References

1. Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19). Updated Jun 10, 2020. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html.

2. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.

3. Westafer LM et al. A transdisciplinary COVID-19 early respiratory intervention protocol: An implementation story. J Hosp Med. 2020 May 21;15(6):372-374.

4. Miller J. “Heroes on the front line: Dr. Raghuveer Rakasi.” Coverage. May 18, 2020. https://coverage.bluecrossma.com/article/heroes-front-line-dr-raghuveer-rakasi

The challenges posed by COVID-19 have crippled health care systems around the globe. By February 2020, the first outbreak in the United States had been set off in Washington State. We quickly became the world’s epicenter of the epidemic, with over 1.8 million patients and over 110,000 deaths.¹ The rapidity of spread and the severity of the disease created a tremendous strain on resources. It blindsided policymakers and hospital administrators, which left little time to react to the challenges placed on hospital operations all over the country.

The necessity of a new care model

Although health systems in the United States are adept in managing complications of common seasonal viral respiratory illnesses, COVID-19 presented an entirely different challenge with its significantly higher mortality rate. A respiratory disease turning into a multiorgan disease that causes debilitating cardiac, renal, neurological, hematological, and psychosocial complications² was not something we had experience managing effectively. Additional challenges included a massive surge of COVID-19 patients, a limited supply of personal protective equipment (PPE), an inadequate number of intensivists for managing the anticipated ventilated patients, and most importantly, the potential of losing some of our workforce if they became infected.

Based on the experiences in China and Italy, and various predictive models, the division of hospital medicine at Baystate Health quickly realized the necessity of a new model of care for COVID-19 patients. We came up with an elaborate plan to manage the disease burden and the strain on resources effectively. The measures we put in place could be broadly divided into three categories following the timeline of the disease: the preparatory phase, the execution phase, and the maintenance phase.
 

The preparatory phase: From “Hospitalists” to “COVIDists”

As in most hospitals around the country, hospitalists are the backbone of inpatient clinical operations at our health system. A focused group of 10 hospitalists who volunteered to take care of COVID-19 patients with a particular interest in the pandemic and experience in critical care were selected, and the term “COVIDists” was coined to refer to them.

COVIDists were trained in various treatment protocols and ongoing clinical trials. They were given refresher training in Advanced Cardiac Life Support (ACLS) and Fundamental Critical Care Support (FCCS) courses and were taught in critical care/ventilator management by the intensivists through rapid indoctrination in the ICU. All of them had their N-95 mask fitting updated and were trained in the safe donning and doffing of all kinds of PPE by PPE coaches. The palliative care team trained them in conducting end-of-life/code status discussions with a focus on being unable to speak with family members at the bedside. COVIDists were also assigned as Code Blue leaders for any “COVID code blue” in the hospital.

In addition to the rapid training course, COVID-related updates were disseminated daily using three different modalities: brief huddles at the start of the day with the COVIDists; a COVID-19 newsletter summarizing daily updates, new treatments, strategies, and policies; and a WhatsApp group for instantly broadcasting information to the COVIDists (Table 1).

The execution phase

All the hospitalized COVID-19 patients were grouped together to COVID units, and the COVIDists were deployed to those units geographically. COVIDists were given lighter than usual patient loads to deal with the extra time needed for donning and doffing of PPE and for coordination with specialists. COVIDists were almost the only clinicians physically visiting the patients in most cases, and they became the “eyes and ears” of specialists since the specialists were advised to minimize exposure and pursue telemedicine consults. The COVIDists were also undertaking the most challenging part of the care – talking to families about end-of-life issues and the futility of aggressive care in certain patients with preexisting conditions.

Some COVIDists were deployed to the ICU to work alongside the intensivists and became an invaluable resource in ICU management when the ICU census skyrocketed during the initial phase of the outbreak. This helped in tiding the health system over during the initial crisis. Within a short time, we shifted away from an early intubation strategy, and most of the ICU patients were managed in the intermediate care units on high flow oxygen along with the awake-proning protocol. The COVIDists exclusively managed these units. They led multidisciplinary rounds two times a day with the ICU, rapid response team (RRT), the palliative care team, and the nursing team. This step drastically decreased the number of intubations, RRT activations, reduced ICU census,³ and helped with hospital capacity and patient flow (Tables 2 and 3).

The maintenance phase

It is already 2 months since the first devising COVIDists. There is no difference in sick callouts between COVIDists and non-COVIDists. One COVIDist and one non-COVIDist contracted the disease, but none of them required hospitalization. Although we initially thought that COVIDists would be needed for only a short period of time, the evolution of the disease is showing signs that it might be prolonged over the next several months. Hence, we are planning to continue COVIDist service for at least the next 6 months and reevaluate the need.

Hospital medicine leadership checked on COVIDists daily in regard to their physical health and, more importantly, their mental well-being. They were offered the chance to be taken off the schedule if they felt burned out, but no one wanted to come off their scheduled service before finishing their shifts. BlueCross MA recognized one of the COVIDists, Raghuveer Rakasi, MD, as a “hero on the front line.”⁴ In Dr. Rakasi’s words, “We took a nosedive into something without knowing its depth, and aware that we could have fatalities among ourselves. We took up new roles, faced new challenges, learned new things every day, evolving every step of the way. We had to change the way we practice medicine, finding new ways to treat patients, and protecting the workforce by limiting patient exposure, prioritizing investigations.” He added that “we have to adapt to a new normal; we should be prepared for this to come in waves. Putting aside our political views, we should stand united 6 feet apart, with a mask covering our brave faces, frequently washing our helping hands to overcome these uncertain times.”
 

Conclusion

The creation of a focused group of hospitalists called COVIDists and providing them with structured and rapid training (in various aspects of clinical care of COVID-19 patients, critical care/ventilator management, efficient and safe use of PPE) and daily information dissemination allowed our health system to prepare for the large volume of COVID-19 patients. It also helped in preserving the larger hospital workforce for a possible future surge.

The rapid development and implementation of the COVIDist strategy succeeded because of the intrinsic motivation of the providers to improve the outcomes of this high-risk patient population and the close collaboration of the stakeholders. Our institution remains successful in managing the pandemic in Western Massachusetts, with reserve capacity remaining even during the peak of the epidemic. A large part of this was because of creating and training a pool of COVIDists.
 

Dr. Medarametla is medical director, clinical operations, in the division of hospital medicine at Baystate Health, and assistant professor at University of Massachusetts, Worcester. Readers can contact him at Venkatrao.MedarametlaMD@Baystatehealth.org. Dr. Prabhakaran is unit medical director, geriatrics unit, in the division of hospital medicine at Baystate Health and assistant professor at University of Massachusetts. Dr. Bryson is associate program director of the Internal Medicine Residency at Baystate Health and assistant professor at University of Massachusetts. Dr. Umar is medical director, clinical operations, in the division of hospital medicine at Baystate Health. Dr. Natanasabapathy is division chief of hospital medicine at Baystate Health and assistant professor at University of Massachusetts.

References

1. Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19). Updated Jun 10, 2020. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html.

2. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.

3. Westafer LM et al. A transdisciplinary COVID-19 early respiratory intervention protocol: An implementation story. J Hosp Med. 2020 May 21;15(6):372-374.

4. Miller J. “Heroes on the front line: Dr. Raghuveer Rakasi.” Coverage. May 18, 2020. https://coverage.bluecrossma.com/article/heroes-front-line-dr-raghuveer-rakasi

Treatment of patients with type 2 diabetes with the SGLT2 inhibitor dapagliflozin led to a significant drop in the occurrence of ‘fast decline’ of renal function in more than 15,000 patients enrolled in the drug’s main cardiovascular outcome trial, another example of the potent renal protective effects of agents from this drug class.

Courtesy Joslin Diabetes Center

Among patients with type 2 diabetes enrolled in the DECLARE-TIMI 58 trial, the incidence of a fast decline in renal function, defined as a drop in estimated glomerular filtration rate (eGFR) of at least 3 mL/min per 1.73 m², was 27% among patients treated with dapagliflozin and 37% in control patients who received placebo, a statistically significant difference for this post-hoc analysis, Itamar Raz, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

This finding, which adds to a long list of other renal function parameters reported to have been improved by treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors, “emphasizes the value of SGLT2 inhibitors as an important component of both prevention and treatment of chronic kidney disease among patients with type 2 diabetes,” said Dr. Raz, a diabetes researcher and professor of medicine at Hadassah University Hospital in Jerusalem.

The primary, prespecified renal outcomes in DECLARE-TIMI 58 were a cardiorenal composite outcome of sustained decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m², end-stage renal disease (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR of less than 15 mL/min per 1.73 m²), or death from renal or cardiovascular causes; and a second prespecified renal-specific composite outcome that was the same except for excluding death from cardiovascular causes. The results showed that the cardiorenal outcome dropped by a statistically significant 24% with dapagliflozin treatment relative to control patients, and the renal-specific outcome fell by a statistically significant 47% with dapagliflozin relative to control patients (Lancet Diab Endocrinol. 2019 Aug 1;7[8];606-17).

The new findings on the incidence of fast decline in renal function help to further flesh out the scope of renal benefit exerted by SGLT2 inhibitors like dapagliflozin in patients with type 2 diabetes, said experts. Fast decline is a relatively recently devised measure of a high-risk, precipitous loss of renal function that has been defined as a drop of either 3 or 5 mL/min per 1.73 m² per year (Kidney Int. 2017 Jun;91[6]:1300-11); for this analysis Dr. Raz and his associates used the less stringent definition.
 

Finding and treating ‘fast decliners’

The new report from Dr. Raz “confirms the original [renal] findings and looks to expand them to a particularly high risk group: the fast decliners,” commented Robert A. Gabbay, MD, chief science & medical officer of the ADA. “In some ways, the group of patients that we need to find a better treatment for most are those whose GFR declines quickly. We don’t always know who they are until after the fact, and studies have been looking for markers that might prospectively identify them,” he said in an interview.

The new analysis showed that dapagliflozin “was effective in this subgroup of patients. Furthermore, it didn’t matter if they had significant baseline disease or not. Even people with normal kidney function [at baseline] who were still fast decliners fared better with the drug than without it. This suggests that, if it can be confirmed in a prospective study, dapagliflozin might be effective very early in the course of treatment if we can identify who will be the fast decliners.”

Dr. Raz and his associates had the data necessary to calculate the rates of eGFR decline during the full follow-up period for 15,012 of the 17,160 patients enrolled in DECLARE-TIMI 58, and they found that 4,788 (32%) were fast decliners and 10,224 had a slower rate of renal deterioration. The average annual decline in eGFR during the period from 6 months after study entry through 4 years was 6.3 mL/min per 1.73 m² per year (median of 5.1 mL/min per 1.73 m² per year) among the fast decliners, and zero (median of 0.6 mL/min per 1.73 m² per year) among the other patients.
 

Overcoming dapagliflozin’s initial eGFR reduction

The researchers focused on the 6-month to 4-year period of treatment as more representative of the impact of dapagliflozin because the SGLT2 inhibitors have an established pattern of triggering an initial, moderate decline in eGFR over roughly the first 6 months on the drug, which is similar to what happens to patients who start treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

“Some patients get as much as a 10% decline in eGFR” when SGLT2 inhibitor treatment starts, but “patients do better over time even with this initial hit,” the same way they do on drugs that act on the renin-angiotensin system, explained Silvio E. Inzucchi, MD, an endocrinologist and professor of medicine at Yale University in New Haven who has extensively studied the SGLT2 inhibitors.

The analyses reported by Dr. Raz showed that the protection against fast decline during the 6-month to 4-year period with dapagliflozin treatment was consistent across a range of patient subgroups regardless of age, duration of their type 2 diabetes, their baseline level of hyperglycemia, and their baseline eGFR. Nearly half the patients enrolled in DECLARE-TIMI 58 had an eGFR at baseline of at least 91 mL/min per 1.73 m² and in this subgroup the incidence of fast decliners was 23% with dapagliflozin and 31% on placebo. Among the 45% of patients who began with an eGFR of 60-90 mL/min per 1.73 m² the fast-decliner incidence was 32% and 43% when on or off dapagliflozin. Among the 7% of patients who entered with an eGFR below 60 mL/min per 1.73 m², the fast-decliner incidence was 25% on dapagliflozin and 36% among controls. All the between-group differences were statistically significant.

The incidence of fast decliners was also lower with dapagliflozin treatment when the analysis included the entire first 4 years on treatment, including the first 6 months when SGLT2s usually spikes a loss of renal function. For the entire 4-year period, fast decline occurred among 34% of patients on dapagliflozin and in 37% of control patients, a statistically significant difference.

The mechanisms behind the consistent renal-protective effects of the SGLT2 inhibitors remain unclear right now, but likely seem related to the “perfect” diuretic action the drugs produce, said Dr. Inzucchi. “They’re not as hugely effective as diuretics, but they’re gentler.” While the SGLT2 inhibitors cause a modest amount of fluid loss ”for some reason they don’t activate the compensatory mechanisms that prevent further reductions in plasma volume,” a property that manifests as little or no change in catecholamines or renin-angiotensin activity, which sets this diuretic action apart from what happens with conventional diuretic drugs, he said in an interview.

In DECLARE-TIMI 58 treatment with dapagliflozin met its primary safety outcome of noninferiority to placebo with respect to major adverse cardiovascular events. The results failed to show statistically significant superiority for one of the primary efficacy endpoints, the rate of major adverse coronary events, but they did show significantly better performance for the second primary efficacy outcome of the rate of cardiovascular death or hospitalization for heart failure, which occurred in 4.9% of patients treated with dapagliflozin and in 5.8% of the control patients during a median follow-up of 4.2 years (N Engl J Med. 2019 Jan 24;380[4]:347-57).

DECLARE-TIMI 58 was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Raz has been an advisor to and speaker on behalf of AstraZeneca as well as several other companies. Dr. Gabbay had no relevant disclosures. Dr. Inzucchi has been a consultant to AstraZeneca, and also to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.

mzoler@mdedge.com

SOURCE: Raz I et al. ADA 2020, Abstract 303-OR.

Treatment of patients with type 2 diabetes with the SGLT2 inhibitor dapagliflozin led to a significant drop in the occurrence of ‘fast decline’ of renal function in more than 15,000 patients enrolled in the drug’s main cardiovascular outcome trial, another example of the potent renal protective effects of agents from this drug class.

Courtesy Joslin Diabetes Center

Among patients with type 2 diabetes enrolled in the DECLARE-TIMI 58 trial, the incidence of a fast decline in renal function, defined as a drop in estimated glomerular filtration rate (eGFR) of at least 3 mL/min per 1.73 m², was 27% among patients treated with dapagliflozin and 37% in control patients who received placebo, a statistically significant difference for this post-hoc analysis, Itamar Raz, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

This finding, which adds to a long list of other renal function parameters reported to have been improved by treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors, “emphasizes the value of SGLT2 inhibitors as an important component of both prevention and treatment of chronic kidney disease among patients with type 2 diabetes,” said Dr. Raz, a diabetes researcher and professor of medicine at Hadassah University Hospital in Jerusalem.

The primary, prespecified renal outcomes in DECLARE-TIMI 58 were a cardiorenal composite outcome of sustained decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m², end-stage renal disease (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR of less than 15 mL/min per 1.73 m²), or death from renal or cardiovascular causes; and a second prespecified renal-specific composite outcome that was the same except for excluding death from cardiovascular causes. The results showed that the cardiorenal outcome dropped by a statistically significant 24% with dapagliflozin treatment relative to control patients, and the renal-specific outcome fell by a statistically significant 47% with dapagliflozin relative to control patients (Lancet Diab Endocrinol. 2019 Aug 1;7[8];606-17).

The new findings on the incidence of fast decline in renal function help to further flesh out the scope of renal benefit exerted by SGLT2 inhibitors like dapagliflozin in patients with type 2 diabetes, said experts. Fast decline is a relatively recently devised measure of a high-risk, precipitous loss of renal function that has been defined as a drop of either 3 or 5 mL/min per 1.73 m² per year (Kidney Int. 2017 Jun;91[6]:1300-11); for this analysis Dr. Raz and his associates used the less stringent definition.
 

Finding and treating ‘fast decliners’

The new report from Dr. Raz “confirms the original [renal] findings and looks to expand them to a particularly high risk group: the fast decliners,” commented Robert A. Gabbay, MD, chief science & medical officer of the ADA. “In some ways, the group of patients that we need to find a better treatment for most are those whose GFR declines quickly. We don’t always know who they are until after the fact, and studies have been looking for markers that might prospectively identify them,” he said in an interview.

The new analysis showed that dapagliflozin “was effective in this subgroup of patients. Furthermore, it didn’t matter if they had significant baseline disease or not. Even people with normal kidney function [at baseline] who were still fast decliners fared better with the drug than without it. This suggests that, if it can be confirmed in a prospective study, dapagliflozin might be effective very early in the course of treatment if we can identify who will be the fast decliners.”

Dr. Raz and his associates had the data necessary to calculate the rates of eGFR decline during the full follow-up period for 15,012 of the 17,160 patients enrolled in DECLARE-TIMI 58, and they found that 4,788 (32%) were fast decliners and 10,224 had a slower rate of renal deterioration. The average annual decline in eGFR during the period from 6 months after study entry through 4 years was 6.3 mL/min per 1.73 m² per year (median of 5.1 mL/min per 1.73 m² per year) among the fast decliners, and zero (median of 0.6 mL/min per 1.73 m² per year) among the other patients.
 

Overcoming dapagliflozin’s initial eGFR reduction

The researchers focused on the 6-month to 4-year period of treatment as more representative of the impact of dapagliflozin because the SGLT2 inhibitors have an established pattern of triggering an initial, moderate decline in eGFR over roughly the first 6 months on the drug, which is similar to what happens to patients who start treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

“Some patients get as much as a 10% decline in eGFR” when SGLT2 inhibitor treatment starts, but “patients do better over time even with this initial hit,” the same way they do on drugs that act on the renin-angiotensin system, explained Silvio E. Inzucchi, MD, an endocrinologist and professor of medicine at Yale University in New Haven who has extensively studied the SGLT2 inhibitors.

The analyses reported by Dr. Raz showed that the protection against fast decline during the 6-month to 4-year period with dapagliflozin treatment was consistent across a range of patient subgroups regardless of age, duration of their type 2 diabetes, their baseline level of hyperglycemia, and their baseline eGFR. Nearly half the patients enrolled in DECLARE-TIMI 58 had an eGFR at baseline of at least 91 mL/min per 1.73 m² and in this subgroup the incidence of fast decliners was 23% with dapagliflozin and 31% on placebo. Among the 45% of patients who began with an eGFR of 60-90 mL/min per 1.73 m² the fast-decliner incidence was 32% and 43% when on or off dapagliflozin. Among the 7% of patients who entered with an eGFR below 60 mL/min per 1.73 m², the fast-decliner incidence was 25% on dapagliflozin and 36% among controls. All the between-group differences were statistically significant.

The incidence of fast decliners was also lower with dapagliflozin treatment when the analysis included the entire first 4 years on treatment, including the first 6 months when SGLT2s usually spikes a loss of renal function. For the entire 4-year period, fast decline occurred among 34% of patients on dapagliflozin and in 37% of control patients, a statistically significant difference.

The mechanisms behind the consistent renal-protective effects of the SGLT2 inhibitors remain unclear right now, but likely seem related to the “perfect” diuretic action the drugs produce, said Dr. Inzucchi. “They’re not as hugely effective as diuretics, but they’re gentler.” While the SGLT2 inhibitors cause a modest amount of fluid loss ”for some reason they don’t activate the compensatory mechanisms that prevent further reductions in plasma volume,” a property that manifests as little or no change in catecholamines or renin-angiotensin activity, which sets this diuretic action apart from what happens with conventional diuretic drugs, he said in an interview.

In DECLARE-TIMI 58 treatment with dapagliflozin met its primary safety outcome of noninferiority to placebo with respect to major adverse cardiovascular events. The results failed to show statistically significant superiority for one of the primary efficacy endpoints, the rate of major adverse coronary events, but they did show significantly better performance for the second primary efficacy outcome of the rate of cardiovascular death or hospitalization for heart failure, which occurred in 4.9% of patients treated with dapagliflozin and in 5.8% of the control patients during a median follow-up of 4.2 years (N Engl J Med. 2019 Jan 24;380[4]:347-57).

DECLARE-TIMI 58 was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Raz has been an advisor to and speaker on behalf of AstraZeneca as well as several other companies. Dr. Gabbay had no relevant disclosures. Dr. Inzucchi has been a consultant to AstraZeneca, and also to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.

mzoler@mdedge.com

SOURCE: Raz I et al. ADA 2020, Abstract 303-OR.

Treatment of patients with type 2 diabetes with the SGLT2 inhibitor dapagliflozin led to a significant drop in the occurrence of ‘fast decline’ of renal function in more than 15,000 patients enrolled in the drug’s main cardiovascular outcome trial, another example of the potent renal protective effects of agents from this drug class.

Courtesy Joslin Diabetes Center

Among patients with type 2 diabetes enrolled in the DECLARE-TIMI 58 trial, the incidence of a fast decline in renal function, defined as a drop in estimated glomerular filtration rate (eGFR) of at least 3 mL/min per 1.73 m², was 27% among patients treated with dapagliflozin and 37% in control patients who received placebo, a statistically significant difference for this post-hoc analysis, Itamar Raz, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

This finding, which adds to a long list of other renal function parameters reported to have been improved by treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors, “emphasizes the value of SGLT2 inhibitors as an important component of both prevention and treatment of chronic kidney disease among patients with type 2 diabetes,” said Dr. Raz, a diabetes researcher and professor of medicine at Hadassah University Hospital in Jerusalem.

The primary, prespecified renal outcomes in DECLARE-TIMI 58 were a cardiorenal composite outcome of sustained decline of at least 40% in eGFR to less than 60 mL/min per 1.73 m², end-stage renal disease (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR of less than 15 mL/min per 1.73 m²), or death from renal or cardiovascular causes; and a second prespecified renal-specific composite outcome that was the same except for excluding death from cardiovascular causes. The results showed that the cardiorenal outcome dropped by a statistically significant 24% with dapagliflozin treatment relative to control patients, and the renal-specific outcome fell by a statistically significant 47% with dapagliflozin relative to control patients (Lancet Diab Endocrinol. 2019 Aug 1;7[8];606-17).

The new findings on the incidence of fast decline in renal function help to further flesh out the scope of renal benefit exerted by SGLT2 inhibitors like dapagliflozin in patients with type 2 diabetes, said experts. Fast decline is a relatively recently devised measure of a high-risk, precipitous loss of renal function that has been defined as a drop of either 3 or 5 mL/min per 1.73 m² per year (Kidney Int. 2017 Jun;91[6]:1300-11); for this analysis Dr. Raz and his associates used the less stringent definition.
 

Finding and treating ‘fast decliners’

The new report from Dr. Raz “confirms the original [renal] findings and looks to expand them to a particularly high risk group: the fast decliners,” commented Robert A. Gabbay, MD, chief science & medical officer of the ADA. “In some ways, the group of patients that we need to find a better treatment for most are those whose GFR declines quickly. We don’t always know who they are until after the fact, and studies have been looking for markers that might prospectively identify them,” he said in an interview.

The new analysis showed that dapagliflozin “was effective in this subgroup of patients. Furthermore, it didn’t matter if they had significant baseline disease or not. Even people with normal kidney function [at baseline] who were still fast decliners fared better with the drug than without it. This suggests that, if it can be confirmed in a prospective study, dapagliflozin might be effective very early in the course of treatment if we can identify who will be the fast decliners.”

Dr. Raz and his associates had the data necessary to calculate the rates of eGFR decline during the full follow-up period for 15,012 of the 17,160 patients enrolled in DECLARE-TIMI 58, and they found that 4,788 (32%) were fast decliners and 10,224 had a slower rate of renal deterioration. The average annual decline in eGFR during the period from 6 months after study entry through 4 years was 6.3 mL/min per 1.73 m² per year (median of 5.1 mL/min per 1.73 m² per year) among the fast decliners, and zero (median of 0.6 mL/min per 1.73 m² per year) among the other patients.
 

Overcoming dapagliflozin’s initial eGFR reduction

The researchers focused on the 6-month to 4-year period of treatment as more representative of the impact of dapagliflozin because the SGLT2 inhibitors have an established pattern of triggering an initial, moderate decline in eGFR over roughly the first 6 months on the drug, which is similar to what happens to patients who start treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

“Some patients get as much as a 10% decline in eGFR” when SGLT2 inhibitor treatment starts, but “patients do better over time even with this initial hit,” the same way they do on drugs that act on the renin-angiotensin system, explained Silvio E. Inzucchi, MD, an endocrinologist and professor of medicine at Yale University in New Haven who has extensively studied the SGLT2 inhibitors.

The analyses reported by Dr. Raz showed that the protection against fast decline during the 6-month to 4-year period with dapagliflozin treatment was consistent across a range of patient subgroups regardless of age, duration of their type 2 diabetes, their baseline level of hyperglycemia, and their baseline eGFR. Nearly half the patients enrolled in DECLARE-TIMI 58 had an eGFR at baseline of at least 91 mL/min per 1.73 m² and in this subgroup the incidence of fast decliners was 23% with dapagliflozin and 31% on placebo. Among the 45% of patients who began with an eGFR of 60-90 mL/min per 1.73 m² the fast-decliner incidence was 32% and 43% when on or off dapagliflozin. Among the 7% of patients who entered with an eGFR below 60 mL/min per 1.73 m², the fast-decliner incidence was 25% on dapagliflozin and 36% among controls. All the between-group differences were statistically significant.

The incidence of fast decliners was also lower with dapagliflozin treatment when the analysis included the entire first 4 years on treatment, including the first 6 months when SGLT2s usually spikes a loss of renal function. For the entire 4-year period, fast decline occurred among 34% of patients on dapagliflozin and in 37% of control patients, a statistically significant difference.

The mechanisms behind the consistent renal-protective effects of the SGLT2 inhibitors remain unclear right now, but likely seem related to the “perfect” diuretic action the drugs produce, said Dr. Inzucchi. “They’re not as hugely effective as diuretics, but they’re gentler.” While the SGLT2 inhibitors cause a modest amount of fluid loss ”for some reason they don’t activate the compensatory mechanisms that prevent further reductions in plasma volume,” a property that manifests as little or no change in catecholamines or renin-angiotensin activity, which sets this diuretic action apart from what happens with conventional diuretic drugs, he said in an interview.

In DECLARE-TIMI 58 treatment with dapagliflozin met its primary safety outcome of noninferiority to placebo with respect to major adverse cardiovascular events. The results failed to show statistically significant superiority for one of the primary efficacy endpoints, the rate of major adverse coronary events, but they did show significantly better performance for the second primary efficacy outcome of the rate of cardiovascular death or hospitalization for heart failure, which occurred in 4.9% of patients treated with dapagliflozin and in 5.8% of the control patients during a median follow-up of 4.2 years (N Engl J Med. 2019 Jan 24;380[4]:347-57).

DECLARE-TIMI 58 was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Raz has been an advisor to and speaker on behalf of AstraZeneca as well as several other companies. Dr. Gabbay had no relevant disclosures. Dr. Inzucchi has been a consultant to AstraZeneca, and also to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics.

mzoler@mdedge.com

SOURCE: Raz I et al. ADA 2020, Abstract 303-OR.

I have an automatic preference for white people over black people. This isn’t my opinion; rather, it is my implicit bias test result. I didn’t believe it at first. Trying hard to not be biased, I took the test again and received the same outcome. My reaction – disbelief – is typical for those like me: White people who believe they are good human beings. I might be good, but that doesn’t mean I’m free of bias or exonerated from the harm being inflicted on people of color.

We’ve all watched in horror the acts of violence against blacks in the news. I was shocked and disgusted. It was easy to believe, however, that I am in no way complicit in the injustice and racism I was watching. I think I’m fair and without prejudice. I have never intentionally discriminated against someone. Wanting to help, I listened to my black colleagues, staff, and patients. What I learned made me uncomfortable.

Through all this news, I’d said little to my colleagues and friends. I cannot identify with how a black person has felt recently. What if I said the wrong thing or caused offense? The safe option is to say nothing. I learned that this is a common reaction and the least helpful. The advice from one black colleague was simple: “Just ask us.” Instead of ignoring the issue, she advised me to say: “I wonder what this experience has been like for you. Would you like to share?” And, if you mean it, to add, “I stand with you.” The latter should be followed by “What can I do to help?” Or, more powerfully, “What have I done that makes me complicit?”

Some of these conversations will be uncomfortable. If you want to help, then sit with that. Feeling uncomfortable might mean you are beginning to understand.

I also heard about the excellent book “White Fragility,” by Robin DiAngelo, PhD. In it, she argues that it is difficult for white people to talk about racism because of a tendency to react with defensiveness, guilt, and sometimes anger.

Many of the chapters in the book were easy to read because they didn’t apply to me: I don’t get angry in equity, inclusion, and diversity meetings. I don’t resent affirmative action programs. But then Dr. DiAngelo got me: I believed because I’m a good person and I have no intention of being racist, I’m absolved. Her argument was enlightening. Like all white people in the United States, I have benefited from white privilege. Yes, I’ve worked hard, but I also grew up in a white family with a college-educated father. That alone afforded me academic and financial advantages, which pushed me ahead. I’ve benefited from the status quo.

I have also failed to speak up when white friends carried on about how unnecessary affirmative action programs have become. I’ve sat with sealed lips when I’ve heard comments like “As a white male, it’s a lot harder to get into prestigious schools now.” Having no intention to harm doesn’t matter; plenty of harm is done unintentionally.

I also believed that because I have good intentions, I have no racial bias. I was wrong. The test I took online is an excellent tool to combat this blind spot. It was created by Harvard researchers and is available to everyone: Take a Test. It asks you to categorize faces as good or bad and records your tiny reaction times. Based on these and other questions, it provides feedback on your personal biases.

I was surprised that I have an implicit preference for white people over black people. That’s the point. Most of us are unaware of our biases and falsely believe we are free of them. I encourage you to take the test and learn about yourself. If the result makes you uncomfortable, then sit with it. Try not to be defensive, as I was, and accept that, even if you are a good person, you can become a better one.

Based on what I’ve learned and heard in the last few weeks, I’ve committed to a few things: To acknowledge the harm done to my black and brown colleagues and my complicity even by acts of omission. To not avoid uncomfortable feelings or uncomfortable conversations. As a leader, to use my organizational status to advocate. To stand by my partners of color not only in dramatic one-time marches but also against the everyday perpetrators of microaggressions. To create a safe space and invite my colleagues, staff, friends, and patients to share.

Standing up against racism is all our responsibility. As Dr. Martin Luther King Jr. reminds us: “In the end, we will remember not the words of our enemies, but the silence of our friends.”
 

Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. He has no disclosures related to this column. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

I have an automatic preference for white people over black people. This isn’t my opinion; rather, it is my implicit bias test result. I didn’t believe it at first. Trying hard to not be biased, I took the test again and received the same outcome. My reaction – disbelief – is typical for those like me: White people who believe they are good human beings. I might be good, but that doesn’t mean I’m free of bias or exonerated from the harm being inflicted on people of color.

We’ve all watched in horror the acts of violence against blacks in the news. I was shocked and disgusted. It was easy to believe, however, that I am in no way complicit in the injustice and racism I was watching. I think I’m fair and without prejudice. I have never intentionally discriminated against someone. Wanting to help, I listened to my black colleagues, staff, and patients. What I learned made me uncomfortable.

Through all this news, I’d said little to my colleagues and friends. I cannot identify with how a black person has felt recently. What if I said the wrong thing or caused offense? The safe option is to say nothing. I learned that this is a common reaction and the least helpful. The advice from one black colleague was simple: “Just ask us.” Instead of ignoring the issue, she advised me to say: “I wonder what this experience has been like for you. Would you like to share?” And, if you mean it, to add, “I stand with you.” The latter should be followed by “What can I do to help?” Or, more powerfully, “What have I done that makes me complicit?”

Some of these conversations will be uncomfortable. If you want to help, then sit with that. Feeling uncomfortable might mean you are beginning to understand.

I also heard about the excellent book “White Fragility,” by Robin DiAngelo, PhD. In it, she argues that it is difficult for white people to talk about racism because of a tendency to react with defensiveness, guilt, and sometimes anger.

Many of the chapters in the book were easy to read because they didn’t apply to me: I don’t get angry in equity, inclusion, and diversity meetings. I don’t resent affirmative action programs. But then Dr. DiAngelo got me: I believed because I’m a good person and I have no intention of being racist, I’m absolved. Her argument was enlightening. Like all white people in the United States, I have benefited from white privilege. Yes, I’ve worked hard, but I also grew up in a white family with a college-educated father. That alone afforded me academic and financial advantages, which pushed me ahead. I’ve benefited from the status quo.

I have also failed to speak up when white friends carried on about how unnecessary affirmative action programs have become. I’ve sat with sealed lips when I’ve heard comments like “As a white male, it’s a lot harder to get into prestigious schools now.” Having no intention to harm doesn’t matter; plenty of harm is done unintentionally.

I also believed that because I have good intentions, I have no racial bias. I was wrong. The test I took online is an excellent tool to combat this blind spot. It was created by Harvard researchers and is available to everyone: Take a Test. It asks you to categorize faces as good or bad and records your tiny reaction times. Based on these and other questions, it provides feedback on your personal biases.

I was surprised that I have an implicit preference for white people over black people. That’s the point. Most of us are unaware of our biases and falsely believe we are free of them. I encourage you to take the test and learn about yourself. If the result makes you uncomfortable, then sit with it. Try not to be defensive, as I was, and accept that, even if you are a good person, you can become a better one.

Based on what I’ve learned and heard in the last few weeks, I’ve committed to a few things: To acknowledge the harm done to my black and brown colleagues and my complicity even by acts of omission. To not avoid uncomfortable feelings or uncomfortable conversations. As a leader, to use my organizational status to advocate. To stand by my partners of color not only in dramatic one-time marches but also against the everyday perpetrators of microaggressions. To create a safe space and invite my colleagues, staff, friends, and patients to share.

Standing up against racism is all our responsibility. As Dr. Martin Luther King Jr. reminds us: “In the end, we will remember not the words of our enemies, but the silence of our friends.”
 

Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. He has no disclosures related to this column. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

I have an automatic preference for white people over black people. This isn’t my opinion; rather, it is my implicit bias test result. I didn’t believe it at first. Trying hard to not be biased, I took the test again and received the same outcome. My reaction – disbelief – is typical for those like me: White people who believe they are good human beings. I might be good, but that doesn’t mean I’m free of bias or exonerated from the harm being inflicted on people of color.

We’ve all watched in horror the acts of violence against blacks in the news. I was shocked and disgusted. It was easy to believe, however, that I am in no way complicit in the injustice and racism I was watching. I think I’m fair and without prejudice. I have never intentionally discriminated against someone. Wanting to help, I listened to my black colleagues, staff, and patients. What I learned made me uncomfortable.

Through all this news, I’d said little to my colleagues and friends. I cannot identify with how a black person has felt recently. What if I said the wrong thing or caused offense? The safe option is to say nothing. I learned that this is a common reaction and the least helpful. The advice from one black colleague was simple: “Just ask us.” Instead of ignoring the issue, she advised me to say: “I wonder what this experience has been like for you. Would you like to share?” And, if you mean it, to add, “I stand with you.” The latter should be followed by “What can I do to help?” Or, more powerfully, “What have I done that makes me complicit?”

Some of these conversations will be uncomfortable. If you want to help, then sit with that. Feeling uncomfortable might mean you are beginning to understand.

I also heard about the excellent book “White Fragility,” by Robin DiAngelo, PhD. In it, she argues that it is difficult for white people to talk about racism because of a tendency to react with defensiveness, guilt, and sometimes anger.

Many of the chapters in the book were easy to read because they didn’t apply to me: I don’t get angry in equity, inclusion, and diversity meetings. I don’t resent affirmative action programs. But then Dr. DiAngelo got me: I believed because I’m a good person and I have no intention of being racist, I’m absolved. Her argument was enlightening. Like all white people in the United States, I have benefited from white privilege. Yes, I’ve worked hard, but I also grew up in a white family with a college-educated father. That alone afforded me academic and financial advantages, which pushed me ahead. I’ve benefited from the status quo.

I have also failed to speak up when white friends carried on about how unnecessary affirmative action programs have become. I’ve sat with sealed lips when I’ve heard comments like “As a white male, it’s a lot harder to get into prestigious schools now.” Having no intention to harm doesn’t matter; plenty of harm is done unintentionally.

I also believed that because I have good intentions, I have no racial bias. I was wrong. The test I took online is an excellent tool to combat this blind spot. It was created by Harvard researchers and is available to everyone: Take a Test. It asks you to categorize faces as good or bad and records your tiny reaction times. Based on these and other questions, it provides feedback on your personal biases.

I was surprised that I have an implicit preference for white people over black people. That’s the point. Most of us are unaware of our biases and falsely believe we are free of them. I encourage you to take the test and learn about yourself. If the result makes you uncomfortable, then sit with it. Try not to be defensive, as I was, and accept that, even if you are a good person, you can become a better one.

Based on what I’ve learned and heard in the last few weeks, I’ve committed to a few things: To acknowledge the harm done to my black and brown colleagues and my complicity even by acts of omission. To not avoid uncomfortable feelings or uncomfortable conversations. As a leader, to use my organizational status to advocate. To stand by my partners of color not only in dramatic one-time marches but also against the everyday perpetrators of microaggressions. To create a safe space and invite my colleagues, staff, friends, and patients to share.

Standing up against racism is all our responsibility. As Dr. Martin Luther King Jr. reminds us: “In the end, we will remember not the words of our enemies, but the silence of our friends.”
 

Dr. Benabio is director of healthcare transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. He has no disclosures related to this column. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Lung ultrasound has “high concordance” with radiologic findings in children with COVID-19, researchers wrote in Pediatrics.

They also noted the benefits that modality provides over other imaging techniques.

Marco Denina, MD, and colleagues from the pediatric infectious diseases unit at Regina Margherita Children’s Hospital in Turin, Italy, performed an observational study of eight children aged 0-17 years who were admitted to the hospital for COVID-19 between March 8 and 26, 2020. In seven of eight patients, the findings were concordant between imaging modalities; in the remaining patient, lung ultrasound (LUS) found an interstitial B-lines pattern that was not seen on radiography. In seven patients with pathologic ultrasound findings at baseline, the improvement or resolution of the subpleural consolidations or interstitial patterns was consistent with concomitant radiologic findings.

The authors cited the benefits of using point-of-care ultrasound instead of other modalities, such as CT. “First, it may reduce the number of radiologic examinations, lowering the radiation exposure of the patients,” they wrote. “Secondly, when performed at the bedside, LUS allows for the reduction of the patient’s movement within the hospital; thus, it lowers the number of health care workers and medical devices exposed to [SARS-CoV-2].”

One limitation of the study is the small sample size; however, the researchers felt the high concordance still suggests LUS is a reasonable method for COVID-19 patients.

There was no external funding for this study and the investigators had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Denina M et al. Pediatrics. 2020 Jun. doi: 10.1542/peds.2020-1157.

Lung ultrasound has “high concordance” with radiologic findings in children with COVID-19, researchers wrote in Pediatrics.

They also noted the benefits that modality provides over other imaging techniques.

Marco Denina, MD, and colleagues from the pediatric infectious diseases unit at Regina Margherita Children’s Hospital in Turin, Italy, performed an observational study of eight children aged 0-17 years who were admitted to the hospital for COVID-19 between March 8 and 26, 2020. In seven of eight patients, the findings were concordant between imaging modalities; in the remaining patient, lung ultrasound (LUS) found an interstitial B-lines pattern that was not seen on radiography. In seven patients with pathologic ultrasound findings at baseline, the improvement or resolution of the subpleural consolidations or interstitial patterns was consistent with concomitant radiologic findings.

The authors cited the benefits of using point-of-care ultrasound instead of other modalities, such as CT. “First, it may reduce the number of radiologic examinations, lowering the radiation exposure of the patients,” they wrote. “Secondly, when performed at the bedside, LUS allows for the reduction of the patient’s movement within the hospital; thus, it lowers the number of health care workers and medical devices exposed to [SARS-CoV-2].”

One limitation of the study is the small sample size; however, the researchers felt the high concordance still suggests LUS is a reasonable method for COVID-19 patients.

There was no external funding for this study and the investigators had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Denina M et al. Pediatrics. 2020 Jun. doi: 10.1542/peds.2020-1157.

Lung ultrasound has “high concordance” with radiologic findings in children with COVID-19, researchers wrote in Pediatrics.

They also noted the benefits that modality provides over other imaging techniques.

Marco Denina, MD, and colleagues from the pediatric infectious diseases unit at Regina Margherita Children’s Hospital in Turin, Italy, performed an observational study of eight children aged 0-17 years who were admitted to the hospital for COVID-19 between March 8 and 26, 2020. In seven of eight patients, the findings were concordant between imaging modalities; in the remaining patient, lung ultrasound (LUS) found an interstitial B-lines pattern that was not seen on radiography. In seven patients with pathologic ultrasound findings at baseline, the improvement or resolution of the subpleural consolidations or interstitial patterns was consistent with concomitant radiologic findings.

The authors cited the benefits of using point-of-care ultrasound instead of other modalities, such as CT. “First, it may reduce the number of radiologic examinations, lowering the radiation exposure of the patients,” they wrote. “Secondly, when performed at the bedside, LUS allows for the reduction of the patient’s movement within the hospital; thus, it lowers the number of health care workers and medical devices exposed to [SARS-CoV-2].”

One limitation of the study is the small sample size; however, the researchers felt the high concordance still suggests LUS is a reasonable method for COVID-19 patients.

There was no external funding for this study and the investigators had no relevant financial disclosures.

cpalmer@mdedge.com

SOURCE: Denina M et al. Pediatrics. 2020 Jun. doi: 10.1542/peds.2020-1157.

The cardiovascular outcome trial results for a fourth sodium-glucose cotransporter 2 (SGLT2) inhibitor, ertugliflozin, were most notable for their consistency with the four prior, similar trials run on the three other drugs from this class on the U.S. market, canagliflozin, dapagliflozin, and empagliflozin, further solidifying the important role this drug class has recently taken on for patients with type 2 diabetes.

But the ertugliflozin results, which showed statistically significant superiority to placebo for just one endpoint, hospitalization for heart failure, made it unclear whether clinicians will regard ertugliflozin as the top agent from this class to prescribe.

“Our big takeaway is that the findings are consistent with what’s been seen in the other studies” of cardiovascular and renal outcomes in the EMPA-REG OUTCOME study of empagliflozin (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ), the CANVAS (N Engl J Med. 2017 Aug 17;377[7]:644-57) and CREDENCE (N Engl J Med. 2019 June 13;380[24]:2295-306 ) studies of canagliflozin, and the DECLARE-TIMI 58 trial with dapagliflozin (N Engl J Med. 2019 Jan 24;380[4]:347-57), Christopher P. Cannon, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The cardiovascular outcome trials (CVOTs), mandated in 2008 by Food and Drug Administration guidance for type 2 diabetes drugs that is now in the process of undergoing an update, have had the main goal of proving safety, and the primary endpoint of the new ertugliflozin trial, VERTIS-CV, was noninferiority to placebo when used on top of standard type 2 diabetes medications for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke.
 

Key findings

Both of the tested dosages of ertugliflozin, 5 mg and 15 mg daily, met this endpoint, with event rates over a median 3.0 years of follow-up that ran very close to the placebo rate, clearly proving noninferiority. But the results showed no suggestion of superiority in a study that randomized 5,499 patients to either of the ertugliflozin regimens and 2,747 to placebo, reported Dr. Cannon, a cardiologist and professor of medicine at Harvard Medical School, Boston.

The primary outcome also showed similar event rates for each component of the composite endpoint, and subgroup analysis showed consistent results from ertugliflozin, compared with placebo, regardless of study-cohort subdivision by demographic, clinical, or treatment factors.

The trial design called for a hierarchical sequence of secondary-outcome superiority analyses, starting with the impact of ertugliflozin on cardiovascular death or heart failure hospitalization, and for this outcome ertugliflozin showed a point estimate of a 12% relative risk reduction, compared with placebo-treated patients, but this difference was not statistically significant. This meant that all subsequent superiority analyses in this trial could only be hypothesis generating and not definitive.

This negated the statistical validity of the only statistically significant treatment difference between ertugliflozin and placebo seen in VERTIS-CV, for the outcome of hospitalization for heart failure, where ertugliflozin treatment cut this outcome by 30%, compared with placebo patients. The rate of cardiovascular death alone, as well as a renal composite endpoint each showed no statistically significant benefit of ertugliflozin, compared with placebo, although the renal endpoint came close, with ertugliflozin reducing the combined rate of renal death, need for dialysis, need for renal transplant, or a doubling of serum creatinine from baseline by 19%, compared with placebo (P = .08).

How results compare with prior CVOTs

In some ways, these results seemed to contrast with outcomes from the CVOTs for the other SGLT2 inhibitors, which all showed at least two statistically significant benefits for major endpoints when compared with placebo.

As summarized in a new meta-analysis of all the CVOTs by Darren K. McGuire, MD, a cardiologist and professor of medicine at the University of Texas, Dallas, both empagliflozin and canagliflozin showed statistically significant superiority compared with placebo for their trial’s primary, combined major cardiovascular adverse event endpoint, but dapagliflozin and ertugliflozin did not. Empagliflozin was the sole SGLT2 inhibitor to show a statistically significant cut in cardiovascular deaths, compared with placebo.

The primary, composite renal efficacy endpoints used in these trials were hardest to compare because they differed from study to study, but unlike ertugliflozin, all the other three drugs in the class showed a statistically significant improvement, compared with placebo, for their respective renal outcomes. On the other hand, the pattern of estimated glomerular filtration rates measured at multiple times during the various trials showed a high level of consistency across the CVOTs.

The greatest consistently among the major endpoints across the trials was for heart failure hospitalization. All four agents showed statistically significant improvements, compared with placebo, and all four had roughly equal magnitudes of effect, a cut in event rates by about one-third.

“The greatest magnitude of benefit is for reductions in heart failure hospitalizations and for renal outcomes,” with the heart failure outcomes the “most consistent” across the studies and the renal outcomes “largely consistent,” concluded Dr. McGuire. All together, the five CVOTs for these four SGLT2 inhibitors involved more than 46,000 patients.

“A lot of data suggest these are all class effects,” that are roughly similar across all four of these SGLT2 inhibitors, commented Mark E. Cooper, MBBS, a professor and head of the department of diabetes at Monash University, Melbourne, and designated discussant for the study.

There was “clear homogeneity” between the VERTIS-CV results for hospitalization for heart failure and the other CVOTs, he noted. “I think there is a difference” in the cardiovascular death outcomes, specifically the sole statistically significant, 38% relative risk reduction with empagliflozin that stood out from the other CVOTs, but this difference is “totally unexplained,” added Dr. Cooper. “To really determine differences you’d need head-to-head studies that are unlikely to happen.”

The results of new SGLT2 inhibitor meta-analysis appeared to also “support contemporary society recommendations to prioritize the use of SGLT2 inhibitors independent of glucose-control considerations in patients with type 2 diabetes with or at high risk for cardiovascular and renal complications,” said Dr. McGuire.

“The guidelines have it right. Now it’s on us to implement these treatments to appropriate patients,” concluded Dr. Cannon.
 

Study details

VERTIS-CV (Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease) enrolled and followed patients with type 2 diabetes and established atherosclerotic cardiovascular disease at 531 centers in 34 countries during December 2013–December 2019. Other effects from ertugliflozin recorded during the trial were consistent with prior studies of the drug, which is already FDA approved for glycemic control: Compared with placebo, ertugliflozin treatment reduced hemoglobin A1c by an average of 0.5% after 1 year, cut average body weight by about 2.5 kg after 1 year with additional modest weight loss, during subsequent years on the drug, and reduced systolic blood pressure by about 3 mm Hg after 1 year.

The drug’s safety profile was generally reassuring and consistent with prior studies of this drug and others in the class, with overall no increase in total adverse events or serious adverse events, compared with placebo, and modestly increased rates of urinary tract and mycotic genital infections.

VERTIS-CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin (Steglatro). Dr. Cannon has received research funding and fees from Merck and Pfizer and from several other companies. Dr. McGuire has received honoraria from Merck, has been a consultant to Pfizer, and has had similar relationships with several other companies. Dr. Cooper has been an advisor to and received honoraria from Merck. He has also received honoraria from or been an adviser to AstraZeneca, Boehringer Ingelheim, Lilly, MundiPharma, Novartis, Reata, and Servier, and he has received research funding from Boehringer Ingelheim and Novo Nordisk.

mzoler@mdedge.com

The cardiovascular outcome trial results for a fourth sodium-glucose cotransporter 2 (SGLT2) inhibitor, ertugliflozin, were most notable for their consistency with the four prior, similar trials run on the three other drugs from this class on the U.S. market, canagliflozin, dapagliflozin, and empagliflozin, further solidifying the important role this drug class has recently taken on for patients with type 2 diabetes.

But the ertugliflozin results, which showed statistically significant superiority to placebo for just one endpoint, hospitalization for heart failure, made it unclear whether clinicians will regard ertugliflozin as the top agent from this class to prescribe.

“Our big takeaway is that the findings are consistent with what’s been seen in the other studies” of cardiovascular and renal outcomes in the EMPA-REG OUTCOME study of empagliflozin (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ), the CANVAS (N Engl J Med. 2017 Aug 17;377[7]:644-57) and CREDENCE (N Engl J Med. 2019 June 13;380[24]:2295-306 ) studies of canagliflozin, and the DECLARE-TIMI 58 trial with dapagliflozin (N Engl J Med. 2019 Jan 24;380[4]:347-57), Christopher P. Cannon, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The cardiovascular outcome trials (CVOTs), mandated in 2008 by Food and Drug Administration guidance for type 2 diabetes drugs that is now in the process of undergoing an update, have had the main goal of proving safety, and the primary endpoint of the new ertugliflozin trial, VERTIS-CV, was noninferiority to placebo when used on top of standard type 2 diabetes medications for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke.
 

Key findings

Both of the tested dosages of ertugliflozin, 5 mg and 15 mg daily, met this endpoint, with event rates over a median 3.0 years of follow-up that ran very close to the placebo rate, clearly proving noninferiority. But the results showed no suggestion of superiority in a study that randomized 5,499 patients to either of the ertugliflozin regimens and 2,747 to placebo, reported Dr. Cannon, a cardiologist and professor of medicine at Harvard Medical School, Boston.

The primary outcome also showed similar event rates for each component of the composite endpoint, and subgroup analysis showed consistent results from ertugliflozin, compared with placebo, regardless of study-cohort subdivision by demographic, clinical, or treatment factors.

The trial design called for a hierarchical sequence of secondary-outcome superiority analyses, starting with the impact of ertugliflozin on cardiovascular death or heart failure hospitalization, and for this outcome ertugliflozin showed a point estimate of a 12% relative risk reduction, compared with placebo-treated patients, but this difference was not statistically significant. This meant that all subsequent superiority analyses in this trial could only be hypothesis generating and not definitive.

This negated the statistical validity of the only statistically significant treatment difference between ertugliflozin and placebo seen in VERTIS-CV, for the outcome of hospitalization for heart failure, where ertugliflozin treatment cut this outcome by 30%, compared with placebo patients. The rate of cardiovascular death alone, as well as a renal composite endpoint each showed no statistically significant benefit of ertugliflozin, compared with placebo, although the renal endpoint came close, with ertugliflozin reducing the combined rate of renal death, need for dialysis, need for renal transplant, or a doubling of serum creatinine from baseline by 19%, compared with placebo (P = .08).

How results compare with prior CVOTs

In some ways, these results seemed to contrast with outcomes from the CVOTs for the other SGLT2 inhibitors, which all showed at least two statistically significant benefits for major endpoints when compared with placebo.

As summarized in a new meta-analysis of all the CVOTs by Darren K. McGuire, MD, a cardiologist and professor of medicine at the University of Texas, Dallas, both empagliflozin and canagliflozin showed statistically significant superiority compared with placebo for their trial’s primary, combined major cardiovascular adverse event endpoint, but dapagliflozin and ertugliflozin did not. Empagliflozin was the sole SGLT2 inhibitor to show a statistically significant cut in cardiovascular deaths, compared with placebo.

The primary, composite renal efficacy endpoints used in these trials were hardest to compare because they differed from study to study, but unlike ertugliflozin, all the other three drugs in the class showed a statistically significant improvement, compared with placebo, for their respective renal outcomes. On the other hand, the pattern of estimated glomerular filtration rates measured at multiple times during the various trials showed a high level of consistency across the CVOTs.

The greatest consistently among the major endpoints across the trials was for heart failure hospitalization. All four agents showed statistically significant improvements, compared with placebo, and all four had roughly equal magnitudes of effect, a cut in event rates by about one-third.

“The greatest magnitude of benefit is for reductions in heart failure hospitalizations and for renal outcomes,” with the heart failure outcomes the “most consistent” across the studies and the renal outcomes “largely consistent,” concluded Dr. McGuire. All together, the five CVOTs for these four SGLT2 inhibitors involved more than 46,000 patients.

“A lot of data suggest these are all class effects,” that are roughly similar across all four of these SGLT2 inhibitors, commented Mark E. Cooper, MBBS, a professor and head of the department of diabetes at Monash University, Melbourne, and designated discussant for the study.

There was “clear homogeneity” between the VERTIS-CV results for hospitalization for heart failure and the other CVOTs, he noted. “I think there is a difference” in the cardiovascular death outcomes, specifically the sole statistically significant, 38% relative risk reduction with empagliflozin that stood out from the other CVOTs, but this difference is “totally unexplained,” added Dr. Cooper. “To really determine differences you’d need head-to-head studies that are unlikely to happen.”

The results of new SGLT2 inhibitor meta-analysis appeared to also “support contemporary society recommendations to prioritize the use of SGLT2 inhibitors independent of glucose-control considerations in patients with type 2 diabetes with or at high risk for cardiovascular and renal complications,” said Dr. McGuire.

“The guidelines have it right. Now it’s on us to implement these treatments to appropriate patients,” concluded Dr. Cannon.
 

Study details

VERTIS-CV (Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease) enrolled and followed patients with type 2 diabetes and established atherosclerotic cardiovascular disease at 531 centers in 34 countries during December 2013–December 2019. Other effects from ertugliflozin recorded during the trial were consistent with prior studies of the drug, which is already FDA approved for glycemic control: Compared with placebo, ertugliflozin treatment reduced hemoglobin A1c by an average of 0.5% after 1 year, cut average body weight by about 2.5 kg after 1 year with additional modest weight loss, during subsequent years on the drug, and reduced systolic blood pressure by about 3 mm Hg after 1 year.

The drug’s safety profile was generally reassuring and consistent with prior studies of this drug and others in the class, with overall no increase in total adverse events or serious adverse events, compared with placebo, and modestly increased rates of urinary tract and mycotic genital infections.

VERTIS-CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin (Steglatro). Dr. Cannon has received research funding and fees from Merck and Pfizer and from several other companies. Dr. McGuire has received honoraria from Merck, has been a consultant to Pfizer, and has had similar relationships with several other companies. Dr. Cooper has been an advisor to and received honoraria from Merck. He has also received honoraria from or been an adviser to AstraZeneca, Boehringer Ingelheim, Lilly, MundiPharma, Novartis, Reata, and Servier, and he has received research funding from Boehringer Ingelheim and Novo Nordisk.

mzoler@mdedge.com

The cardiovascular outcome trial results for a fourth sodium-glucose cotransporter 2 (SGLT2) inhibitor, ertugliflozin, were most notable for their consistency with the four prior, similar trials run on the three other drugs from this class on the U.S. market, canagliflozin, dapagliflozin, and empagliflozin, further solidifying the important role this drug class has recently taken on for patients with type 2 diabetes.

But the ertugliflozin results, which showed statistically significant superiority to placebo for just one endpoint, hospitalization for heart failure, made it unclear whether clinicians will regard ertugliflozin as the top agent from this class to prescribe.

“Our big takeaway is that the findings are consistent with what’s been seen in the other studies” of cardiovascular and renal outcomes in the EMPA-REG OUTCOME study of empagliflozin (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ), the CANVAS (N Engl J Med. 2017 Aug 17;377[7]:644-57) and CREDENCE (N Engl J Med. 2019 June 13;380[24]:2295-306 ) studies of canagliflozin, and the DECLARE-TIMI 58 trial with dapagliflozin (N Engl J Med. 2019 Jan 24;380[4]:347-57), Christopher P. Cannon, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The cardiovascular outcome trials (CVOTs), mandated in 2008 by Food and Drug Administration guidance for type 2 diabetes drugs that is now in the process of undergoing an update, have had the main goal of proving safety, and the primary endpoint of the new ertugliflozin trial, VERTIS-CV, was noninferiority to placebo when used on top of standard type 2 diabetes medications for the combined endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke.
 

Key findings

Both of the tested dosages of ertugliflozin, 5 mg and 15 mg daily, met this endpoint, with event rates over a median 3.0 years of follow-up that ran very close to the placebo rate, clearly proving noninferiority. But the results showed no suggestion of superiority in a study that randomized 5,499 patients to either of the ertugliflozin regimens and 2,747 to placebo, reported Dr. Cannon, a cardiologist and professor of medicine at Harvard Medical School, Boston.

The primary outcome also showed similar event rates for each component of the composite endpoint, and subgroup analysis showed consistent results from ertugliflozin, compared with placebo, regardless of study-cohort subdivision by demographic, clinical, or treatment factors.

The trial design called for a hierarchical sequence of secondary-outcome superiority analyses, starting with the impact of ertugliflozin on cardiovascular death or heart failure hospitalization, and for this outcome ertugliflozin showed a point estimate of a 12% relative risk reduction, compared with placebo-treated patients, but this difference was not statistically significant. This meant that all subsequent superiority analyses in this trial could only be hypothesis generating and not definitive.

This negated the statistical validity of the only statistically significant treatment difference between ertugliflozin and placebo seen in VERTIS-CV, for the outcome of hospitalization for heart failure, where ertugliflozin treatment cut this outcome by 30%, compared with placebo patients. The rate of cardiovascular death alone, as well as a renal composite endpoint each showed no statistically significant benefit of ertugliflozin, compared with placebo, although the renal endpoint came close, with ertugliflozin reducing the combined rate of renal death, need for dialysis, need for renal transplant, or a doubling of serum creatinine from baseline by 19%, compared with placebo (P = .08).

How results compare with prior CVOTs

In some ways, these results seemed to contrast with outcomes from the CVOTs for the other SGLT2 inhibitors, which all showed at least two statistically significant benefits for major endpoints when compared with placebo.

As summarized in a new meta-analysis of all the CVOTs by Darren K. McGuire, MD, a cardiologist and professor of medicine at the University of Texas, Dallas, both empagliflozin and canagliflozin showed statistically significant superiority compared with placebo for their trial’s primary, combined major cardiovascular adverse event endpoint, but dapagliflozin and ertugliflozin did not. Empagliflozin was the sole SGLT2 inhibitor to show a statistically significant cut in cardiovascular deaths, compared with placebo.

The primary, composite renal efficacy endpoints used in these trials were hardest to compare because they differed from study to study, but unlike ertugliflozin, all the other three drugs in the class showed a statistically significant improvement, compared with placebo, for their respective renal outcomes. On the other hand, the pattern of estimated glomerular filtration rates measured at multiple times during the various trials showed a high level of consistency across the CVOTs.

The greatest consistently among the major endpoints across the trials was for heart failure hospitalization. All four agents showed statistically significant improvements, compared with placebo, and all four had roughly equal magnitudes of effect, a cut in event rates by about one-third.

“The greatest magnitude of benefit is for reductions in heart failure hospitalizations and for renal outcomes,” with the heart failure outcomes the “most consistent” across the studies and the renal outcomes “largely consistent,” concluded Dr. McGuire. All together, the five CVOTs for these four SGLT2 inhibitors involved more than 46,000 patients.

“A lot of data suggest these are all class effects,” that are roughly similar across all four of these SGLT2 inhibitors, commented Mark E. Cooper, MBBS, a professor and head of the department of diabetes at Monash University, Melbourne, and designated discussant for the study.

There was “clear homogeneity” between the VERTIS-CV results for hospitalization for heart failure and the other CVOTs, he noted. “I think there is a difference” in the cardiovascular death outcomes, specifically the sole statistically significant, 38% relative risk reduction with empagliflozin that stood out from the other CVOTs, but this difference is “totally unexplained,” added Dr. Cooper. “To really determine differences you’d need head-to-head studies that are unlikely to happen.”

The results of new SGLT2 inhibitor meta-analysis appeared to also “support contemporary society recommendations to prioritize the use of SGLT2 inhibitors independent of glucose-control considerations in patients with type 2 diabetes with or at high risk for cardiovascular and renal complications,” said Dr. McGuire.

“The guidelines have it right. Now it’s on us to implement these treatments to appropriate patients,” concluded Dr. Cannon.
 

Study details

VERTIS-CV (Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease) enrolled and followed patients with type 2 diabetes and established atherosclerotic cardiovascular disease at 531 centers in 34 countries during December 2013–December 2019. Other effects from ertugliflozin recorded during the trial were consistent with prior studies of the drug, which is already FDA approved for glycemic control: Compared with placebo, ertugliflozin treatment reduced hemoglobin A1c by an average of 0.5% after 1 year, cut average body weight by about 2.5 kg after 1 year with additional modest weight loss, during subsequent years on the drug, and reduced systolic blood pressure by about 3 mm Hg after 1 year.

The drug’s safety profile was generally reassuring and consistent with prior studies of this drug and others in the class, with overall no increase in total adverse events or serious adverse events, compared with placebo, and modestly increased rates of urinary tract and mycotic genital infections.

VERTIS-CV was sponsored by Merck and Pfizer, the companies that market ertugliflozin (Steglatro). Dr. Cannon has received research funding and fees from Merck and Pfizer and from several other companies. Dr. McGuire has received honoraria from Merck, has been a consultant to Pfizer, and has had similar relationships with several other companies. Dr. Cooper has been an advisor to and received honoraria from Merck. He has also received honoraria from or been an adviser to AstraZeneca, Boehringer Ingelheim, Lilly, MundiPharma, Novartis, Reata, and Servier, and he has received research funding from Boehringer Ingelheim and Novo Nordisk.

mzoler@mdedge.com

When sterilizing face masks, the type of face mask and the method of sterilization have a bearing on subsequent filtration efficiency, according to researchers. The greatest reduction in filtration efficiency after sterilization occurred with surgical face masks.

With plasma vapor hydrogen peroxide (H₂O₂) sterilization, filtration efficiency of N95 and KN95 masks was maintained at more than 95%, but for surgical face masks, filtration efficiency was reduced to less than 95%. With chlorine dioxide (ClO₂) sterilization, on the other hand, filtration efficiency was maintained at above 95% for N95 masks, but for KN95 and surgical face masks, filtration efficiency was reduced to less than 80%.

In a research letter published online June 15 in JAMA Network Open, researchers from the University of Oklahoma Health Sciences Center, Oklahoma City, report the results of a study of the two sterilization techniques on the pressure drop and filtration efficiency of N95, KN95, and surgical face masks.

“The H₂O₂ treatment showed a small effect on the overall filtration efficiency of the tested masks, but the ClO₂ treatment showed marked reduction in the overall filtration efficiency of the KN95s and surgical face masks. All pressure drop changes were within the acceptable range,” the researchers write.

The study did not evaluate the effect of repeated sterilizations on face masks.

Five masks of each type were sterilized with either H₂O₂ or ClO₂. Masks were then placed in a test chamber, and a salt aerosol was nebulized to assess both upstream and downstream filtration as well as pressure drop. The researchers used a mobility particle sizer to measure particle number concentration from 16.8 nm to 514 nm. An acceptable pressure drop was defined as a drop of less than 1.38 inches of water (35 mm) for inhalation.

Although pressure drop changes were within the acceptable range for all three mask types following sterilization with either method, H₂O₂ sterilization yielded the least reduction in filtration efficacy in all cases. After sterilization with H₂O₂, filtration efficiencies were 96.6%, 97.1%, and 91.6% for the N95s, KN95s, and the surgical face masks, respectively. In contrast, filtration efficiencies after ClO₂ sterilization were 95.1%, 76.2%, and 77.9%, respectively.

The researchers note that, although overall filtration efficiency was maintained with ClO₂ sterilization, there was a significant drop in efficiency with respect to particles of approximately 300 nm (0.3 microns) in size. For particles of that size, mean filtration efficiency decreased to 86.2% for N95s, 40.8% for KN95s, and 47.1% for surgical face masks.

The testing described in the report is “quite affordable at $350 per mask type, so it is hard to imagine any health care provider cannot set aside a small budget to conduct such an important test,” author Evan Floyd, PhD, told Medscape Medical News.

Given the high demand for effective face masks and the current risk for counterfeit products, Floyd suggested that individual facilities test all masks intended for use by healthcare workers before and after sterilization procedures.

“However, if for some reason testing is not an option, we would recommend sticking to established brands and suppliers, perhaps reach out to your state health department or a local representative of the strategic stockpile of PPE,” he noted.

The authors acknowledge that further studies using a larger sample size and a greater variety of masks, as well as studies to evaluate different sterilization techniques, are required. Further, “measuring the respirator’s filtration efficiency by aerosol size instead of only measuring the overall filtration efficiency” should also be considered. Such an approach would enable researchers to evaluate the degree to which masks protect against specific infectious agents.

This article first appeared on Medscape.com.

When sterilizing face masks, the type of face mask and the method of sterilization have a bearing on subsequent filtration efficiency, according to researchers. The greatest reduction in filtration efficiency after sterilization occurred with surgical face masks.

With plasma vapor hydrogen peroxide (H₂O₂) sterilization, filtration efficiency of N95 and KN95 masks was maintained at more than 95%, but for surgical face masks, filtration efficiency was reduced to less than 95%. With chlorine dioxide (ClO₂) sterilization, on the other hand, filtration efficiency was maintained at above 95% for N95 masks, but for KN95 and surgical face masks, filtration efficiency was reduced to less than 80%.

In a research letter published online June 15 in JAMA Network Open, researchers from the University of Oklahoma Health Sciences Center, Oklahoma City, report the results of a study of the two sterilization techniques on the pressure drop and filtration efficiency of N95, KN95, and surgical face masks.

“The H₂O₂ treatment showed a small effect on the overall filtration efficiency of the tested masks, but the ClO₂ treatment showed marked reduction in the overall filtration efficiency of the KN95s and surgical face masks. All pressure drop changes were within the acceptable range,” the researchers write.

The study did not evaluate the effect of repeated sterilizations on face masks.

Five masks of each type were sterilized with either H₂O₂ or ClO₂. Masks were then placed in a test chamber, and a salt aerosol was nebulized to assess both upstream and downstream filtration as well as pressure drop. The researchers used a mobility particle sizer to measure particle number concentration from 16.8 nm to 514 nm. An acceptable pressure drop was defined as a drop of less than 1.38 inches of water (35 mm) for inhalation.

Although pressure drop changes were within the acceptable range for all three mask types following sterilization with either method, H₂O₂ sterilization yielded the least reduction in filtration efficacy in all cases. After sterilization with H₂O₂, filtration efficiencies were 96.6%, 97.1%, and 91.6% for the N95s, KN95s, and the surgical face masks, respectively. In contrast, filtration efficiencies after ClO₂ sterilization were 95.1%, 76.2%, and 77.9%, respectively.

The researchers note that, although overall filtration efficiency was maintained with ClO₂ sterilization, there was a significant drop in efficiency with respect to particles of approximately 300 nm (0.3 microns) in size. For particles of that size, mean filtration efficiency decreased to 86.2% for N95s, 40.8% for KN95s, and 47.1% for surgical face masks.

The testing described in the report is “quite affordable at $350 per mask type, so it is hard to imagine any health care provider cannot set aside a small budget to conduct such an important test,” author Evan Floyd, PhD, told Medscape Medical News.

Given the high demand for effective face masks and the current risk for counterfeit products, Floyd suggested that individual facilities test all masks intended for use by healthcare workers before and after sterilization procedures.

“However, if for some reason testing is not an option, we would recommend sticking to established brands and suppliers, perhaps reach out to your state health department or a local representative of the strategic stockpile of PPE,” he noted.

The authors acknowledge that further studies using a larger sample size and a greater variety of masks, as well as studies to evaluate different sterilization techniques, are required. Further, “measuring the respirator’s filtration efficiency by aerosol size instead of only measuring the overall filtration efficiency” should also be considered. Such an approach would enable researchers to evaluate the degree to which masks protect against specific infectious agents.

This article first appeared on Medscape.com.

When sterilizing face masks, the type of face mask and the method of sterilization have a bearing on subsequent filtration efficiency, according to researchers. The greatest reduction in filtration efficiency after sterilization occurred with surgical face masks.

With plasma vapor hydrogen peroxide (H₂O₂) sterilization, filtration efficiency of N95 and KN95 masks was maintained at more than 95%, but for surgical face masks, filtration efficiency was reduced to less than 95%. With chlorine dioxide (ClO₂) sterilization, on the other hand, filtration efficiency was maintained at above 95% for N95 masks, but for KN95 and surgical face masks, filtration efficiency was reduced to less than 80%.

In a research letter published online June 15 in JAMA Network Open, researchers from the University of Oklahoma Health Sciences Center, Oklahoma City, report the results of a study of the two sterilization techniques on the pressure drop and filtration efficiency of N95, KN95, and surgical face masks.

“The H₂O₂ treatment showed a small effect on the overall filtration efficiency of the tested masks, but the ClO₂ treatment showed marked reduction in the overall filtration efficiency of the KN95s and surgical face masks. All pressure drop changes were within the acceptable range,” the researchers write.

The study did not evaluate the effect of repeated sterilizations on face masks.

Five masks of each type were sterilized with either H₂O₂ or ClO₂. Masks were then placed in a test chamber, and a salt aerosol was nebulized to assess both upstream and downstream filtration as well as pressure drop. The researchers used a mobility particle sizer to measure particle number concentration from 16.8 nm to 514 nm. An acceptable pressure drop was defined as a drop of less than 1.38 inches of water (35 mm) for inhalation.

Although pressure drop changes were within the acceptable range for all three mask types following sterilization with either method, H₂O₂ sterilization yielded the least reduction in filtration efficacy in all cases. After sterilization with H₂O₂, filtration efficiencies were 96.6%, 97.1%, and 91.6% for the N95s, KN95s, and the surgical face masks, respectively. In contrast, filtration efficiencies after ClO₂ sterilization were 95.1%, 76.2%, and 77.9%, respectively.

The researchers note that, although overall filtration efficiency was maintained with ClO₂ sterilization, there was a significant drop in efficiency with respect to particles of approximately 300 nm (0.3 microns) in size. For particles of that size, mean filtration efficiency decreased to 86.2% for N95s, 40.8% for KN95s, and 47.1% for surgical face masks.

The testing described in the report is “quite affordable at $350 per mask type, so it is hard to imagine any health care provider cannot set aside a small budget to conduct such an important test,” author Evan Floyd, PhD, told Medscape Medical News.

Given the high demand for effective face masks and the current risk for counterfeit products, Floyd suggested that individual facilities test all masks intended for use by healthcare workers before and after sterilization procedures.

“However, if for some reason testing is not an option, we would recommend sticking to established brands and suppliers, perhaps reach out to your state health department or a local representative of the strategic stockpile of PPE,” he noted.

The authors acknowledge that further studies using a larger sample size and a greater variety of masks, as well as studies to evaluate different sterilization techniques, are required. Further, “measuring the respirator’s filtration efficiency by aerosol size instead of only measuring the overall filtration efficiency” should also be considered. Such an approach would enable researchers to evaluate the degree to which masks protect against specific infectious agents.

This article first appeared on Medscape.com.

Frequent hypoglycemic episodes were linked to a raised incidence of cardiovascular events in adults with type 2 diabetes in a recent retrospective study, suggesting certain hypoglycemia-associated diabetes drugs should be avoided, an investigator said.

Patients who had more than five hypoglycemic episodes per year had a 61% greater risk of cardiovascular (CV) events, compared with patients with less frequent episodes, according to results of the study.

Although there were fewer strokes among younger patients, the overall increase in cardiovascular event risk held up regardless of age group, according to investigator Aman Rajpal, MD, of Louis Stokes Veterans Affairs Medical Center and Case Western Reserve University, both in Cleveland.

On the basis of these and earlier studies tying hypoglycemia to CV risk, health care providers need to “pay close attention” to low blood sugar and personalize glycemic control targets for each patient based on risk of hypoglycemia, Dr. Rajpal said in a presentation of the study at the virtual annual scientific sessions of the American Diabetes Association.

“Also, this suggests that avoidance of drugs associated with increased risk of hypoglycemia – namely insulin, sulfonylureas, or others – is essential to avoid and minimize the risk of cardiovascular events in this patient population with type 2 diabetes,” said Dr. Rajpal. “Let us remember part of our Hippocratic oath: ‘Above all, do no harm.’ ”
 

Tailoring treatment to mitigate risk

Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, said that results of this study suggest a need to carefully select medical therapy for each individual patient with diabetes in order to mitigate CV risk.

“It’s really about tailoring their drugs to their personal situation,” Dr. Schutta said in an interview.

Although newer diabetes drug classes are associated with low to no risk of hypoglycemia, Dr. Schutta said that there is still a place for drugs such as sulfonylureas in certain situations.

Among sulfonylureas, glyburide comes with a much higher incidence of hypoglycemia, compared with glipizide and glimepiride, according to Dr. Schutta. “I think there’s a role for both drugs, but you have to be very careful, and you have to get the data from your patients.”
 

Hypoglycemia frequency and outcomes

Speculation that hypoglycemia could be linked to adverse CV outcomes was sparked years ago by trials such as ADVANCE. Severe hypoglycemia in that study was associated with a 168% increased risk of death from a CV cause (N Engl J Med. 2010 Oct 7;363:1410-8).

At the time, ADVANCE investigators said they were unable to find evidence that multiple severe hypoglycemia episodes conferred a greater risk of CV events versus a single hypoglycemia episode, though they added that few patients had recurrent events.

“In other words, the association between the number of hypoglycemia events, and adverse CV outcomes is still unclear,” said Dr. Rajpal in his virtual ADA presentation.
 

Potential elevated risks with more than five episodes

To evaluate the association between frequent hypoglycemic episodes (i.e., more than five per year, compared with one to five episodes) and CV events, Dr. Rajpal and colleagues evaluated outcomes data for 4.9 million adults with type 2 diabetes found in a large commercial database including information on patients in 27 U.S. health care networks.

Database records indicated that about 182,000 patients, or nearly 4%, had episodes of hyperglycemia, which Dr. Rajpal said was presumed to mean a plasma glucose level of less than 70 mg/dL.

Characteristics of the patients with more than five hypoglycemic episodes were similar to those with one to five episodes, although they were more likely to be 65 years or older, and were “slightly more likely” to be on insulin, which could possibly precipitate more hypoglycemic episodes in that group, Dr. Rajpal said.
 

Key findings

In the main analysis, Dr. Rajpal said, risk of CV events was significantly increased in those with more than five hypoglycemic episodes, compared with those with one to five episodes, with an odds ratio of 1.61 (95% confidence interval, 1.56-1.66). The incidence of cardiovascular events was 33.1% in those with more than five episodes and 23.5% in those with one to five episodes, according to the data presented.

Risks were also significantly increased specifically for cardiac arrhythmias, cerebrovascular accidents, and MI, Dr. Rajpal said, with ORs of 1.65 (95% CI, 1.9-1.71), 1.38 (95% CI, 1.22-1.56), and 1.43 (95% CI, 1.36-1.50), respectively.

Because individuals in the group with more than five hypoglycemic episodes were more likely to be elderly, Dr. Rajpal said that he and coinvestigators decided to perform an age-specific stratified analysis.

Although cerebral vascular incidence was low in younger patients, risk of CV events overall was nevertheless significantly elevated for those aged 65 years or older, 45-64 years, and 18-44 years, with ORs of 1.69 (95% CI, 1.61-1.7), 1.58 (95% CI, 1.48-1.69), and 1.62 (95% CI, 1.33-1.97).

“The results were still valid in stratified analysis based on different age groups,” Dr. Rajpal said.

Dr. Rajpal and coauthors reported that he had no conflicts of interest related to the research.

SOURCE: Rajpal A et al. ADA 2020, Abstract 161-OR.

Frequent hypoglycemic episodes were linked to a raised incidence of cardiovascular events in adults with type 2 diabetes in a recent retrospective study, suggesting certain hypoglycemia-associated diabetes drugs should be avoided, an investigator said.

Patients who had more than five hypoglycemic episodes per year had a 61% greater risk of cardiovascular (CV) events, compared with patients with less frequent episodes, according to results of the study.

Although there were fewer strokes among younger patients, the overall increase in cardiovascular event risk held up regardless of age group, according to investigator Aman Rajpal, MD, of Louis Stokes Veterans Affairs Medical Center and Case Western Reserve University, both in Cleveland.

On the basis of these and earlier studies tying hypoglycemia to CV risk, health care providers need to “pay close attention” to low blood sugar and personalize glycemic control targets for each patient based on risk of hypoglycemia, Dr. Rajpal said in a presentation of the study at the virtual annual scientific sessions of the American Diabetes Association.

“Also, this suggests that avoidance of drugs associated with increased risk of hypoglycemia – namely insulin, sulfonylureas, or others – is essential to avoid and minimize the risk of cardiovascular events in this patient population with type 2 diabetes,” said Dr. Rajpal. “Let us remember part of our Hippocratic oath: ‘Above all, do no harm.’ ”
 

Tailoring treatment to mitigate risk

Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, said that results of this study suggest a need to carefully select medical therapy for each individual patient with diabetes in order to mitigate CV risk.

“It’s really about tailoring their drugs to their personal situation,” Dr. Schutta said in an interview.

Although newer diabetes drug classes are associated with low to no risk of hypoglycemia, Dr. Schutta said that there is still a place for drugs such as sulfonylureas in certain situations.

Among sulfonylureas, glyburide comes with a much higher incidence of hypoglycemia, compared with glipizide and glimepiride, according to Dr. Schutta. “I think there’s a role for both drugs, but you have to be very careful, and you have to get the data from your patients.”
 

Hypoglycemia frequency and outcomes

Speculation that hypoglycemia could be linked to adverse CV outcomes was sparked years ago by trials such as ADVANCE. Severe hypoglycemia in that study was associated with a 168% increased risk of death from a CV cause (N Engl J Med. 2010 Oct 7;363:1410-8).

At the time, ADVANCE investigators said they were unable to find evidence that multiple severe hypoglycemia episodes conferred a greater risk of CV events versus a single hypoglycemia episode, though they added that few patients had recurrent events.

“In other words, the association between the number of hypoglycemia events, and adverse CV outcomes is still unclear,” said Dr. Rajpal in his virtual ADA presentation.
 

Potential elevated risks with more than five episodes

To evaluate the association between frequent hypoglycemic episodes (i.e., more than five per year, compared with one to five episodes) and CV events, Dr. Rajpal and colleagues evaluated outcomes data for 4.9 million adults with type 2 diabetes found in a large commercial database including information on patients in 27 U.S. health care networks.

Database records indicated that about 182,000 patients, or nearly 4%, had episodes of hyperglycemia, which Dr. Rajpal said was presumed to mean a plasma glucose level of less than 70 mg/dL.

Characteristics of the patients with more than five hypoglycemic episodes were similar to those with one to five episodes, although they were more likely to be 65 years or older, and were “slightly more likely” to be on insulin, which could possibly precipitate more hypoglycemic episodes in that group, Dr. Rajpal said.
 

Key findings

In the main analysis, Dr. Rajpal said, risk of CV events was significantly increased in those with more than five hypoglycemic episodes, compared with those with one to five episodes, with an odds ratio of 1.61 (95% confidence interval, 1.56-1.66). The incidence of cardiovascular events was 33.1% in those with more than five episodes and 23.5% in those with one to five episodes, according to the data presented.

Risks were also significantly increased specifically for cardiac arrhythmias, cerebrovascular accidents, and MI, Dr. Rajpal said, with ORs of 1.65 (95% CI, 1.9-1.71), 1.38 (95% CI, 1.22-1.56), and 1.43 (95% CI, 1.36-1.50), respectively.

Because individuals in the group with more than five hypoglycemic episodes were more likely to be elderly, Dr. Rajpal said that he and coinvestigators decided to perform an age-specific stratified analysis.

Although cerebral vascular incidence was low in younger patients, risk of CV events overall was nevertheless significantly elevated for those aged 65 years or older, 45-64 years, and 18-44 years, with ORs of 1.69 (95% CI, 1.61-1.7), 1.58 (95% CI, 1.48-1.69), and 1.62 (95% CI, 1.33-1.97).

“The results were still valid in stratified analysis based on different age groups,” Dr. Rajpal said.

Dr. Rajpal and coauthors reported that he had no conflicts of interest related to the research.

SOURCE: Rajpal A et al. ADA 2020, Abstract 161-OR.

Frequent hypoglycemic episodes were linked to a raised incidence of cardiovascular events in adults with type 2 diabetes in a recent retrospective study, suggesting certain hypoglycemia-associated diabetes drugs should be avoided, an investigator said.

Patients who had more than five hypoglycemic episodes per year had a 61% greater risk of cardiovascular (CV) events, compared with patients with less frequent episodes, according to results of the study.

Although there were fewer strokes among younger patients, the overall increase in cardiovascular event risk held up regardless of age group, according to investigator Aman Rajpal, MD, of Louis Stokes Veterans Affairs Medical Center and Case Western Reserve University, both in Cleveland.

On the basis of these and earlier studies tying hypoglycemia to CV risk, health care providers need to “pay close attention” to low blood sugar and personalize glycemic control targets for each patient based on risk of hypoglycemia, Dr. Rajpal said in a presentation of the study at the virtual annual scientific sessions of the American Diabetes Association.

“Also, this suggests that avoidance of drugs associated with increased risk of hypoglycemia – namely insulin, sulfonylureas, or others – is essential to avoid and minimize the risk of cardiovascular events in this patient population with type 2 diabetes,” said Dr. Rajpal. “Let us remember part of our Hippocratic oath: ‘Above all, do no harm.’ ”
 

Tailoring treatment to mitigate risk

Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, said that results of this study suggest a need to carefully select medical therapy for each individual patient with diabetes in order to mitigate CV risk.

“It’s really about tailoring their drugs to their personal situation,” Dr. Schutta said in an interview.

Although newer diabetes drug classes are associated with low to no risk of hypoglycemia, Dr. Schutta said that there is still a place for drugs such as sulfonylureas in certain situations.

Among sulfonylureas, glyburide comes with a much higher incidence of hypoglycemia, compared with glipizide and glimepiride, according to Dr. Schutta. “I think there’s a role for both drugs, but you have to be very careful, and you have to get the data from your patients.”
 

Hypoglycemia frequency and outcomes

Speculation that hypoglycemia could be linked to adverse CV outcomes was sparked years ago by trials such as ADVANCE. Severe hypoglycemia in that study was associated with a 168% increased risk of death from a CV cause (N Engl J Med. 2010 Oct 7;363:1410-8).

At the time, ADVANCE investigators said they were unable to find evidence that multiple severe hypoglycemia episodes conferred a greater risk of CV events versus a single hypoglycemia episode, though they added that few patients had recurrent events.

“In other words, the association between the number of hypoglycemia events, and adverse CV outcomes is still unclear,” said Dr. Rajpal in his virtual ADA presentation.
 

Potential elevated risks with more than five episodes

To evaluate the association between frequent hypoglycemic episodes (i.e., more than five per year, compared with one to five episodes) and CV events, Dr. Rajpal and colleagues evaluated outcomes data for 4.9 million adults with type 2 diabetes found in a large commercial database including information on patients in 27 U.S. health care networks.

Database records indicated that about 182,000 patients, or nearly 4%, had episodes of hyperglycemia, which Dr. Rajpal said was presumed to mean a plasma glucose level of less than 70 mg/dL.

Characteristics of the patients with more than five hypoglycemic episodes were similar to those with one to five episodes, although they were more likely to be 65 years or older, and were “slightly more likely” to be on insulin, which could possibly precipitate more hypoglycemic episodes in that group, Dr. Rajpal said.
 

Key findings

In the main analysis, Dr. Rajpal said, risk of CV events was significantly increased in those with more than five hypoglycemic episodes, compared with those with one to five episodes, with an odds ratio of 1.61 (95% confidence interval, 1.56-1.66). The incidence of cardiovascular events was 33.1% in those with more than five episodes and 23.5% in those with one to five episodes, according to the data presented.

Risks were also significantly increased specifically for cardiac arrhythmias, cerebrovascular accidents, and MI, Dr. Rajpal said, with ORs of 1.65 (95% CI, 1.9-1.71), 1.38 (95% CI, 1.22-1.56), and 1.43 (95% CI, 1.36-1.50), respectively.

Because individuals in the group with more than five hypoglycemic episodes were more likely to be elderly, Dr. Rajpal said that he and coinvestigators decided to perform an age-specific stratified analysis.

Although cerebral vascular incidence was low in younger patients, risk of CV events overall was nevertheless significantly elevated for those aged 65 years or older, 45-64 years, and 18-44 years, with ORs of 1.69 (95% CI, 1.61-1.7), 1.58 (95% CI, 1.48-1.69), and 1.62 (95% CI, 1.33-1.97).

“The results were still valid in stratified analysis based on different age groups,” Dr. Rajpal said.

Dr. Rajpal and coauthors reported that he had no conflicts of interest related to the research.

SOURCE: Rajpal A et al. ADA 2020, Abstract 161-OR.