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Long COVID ‘brain fog’ confounds doctors, but new research offers hope
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Finding the optimal fluid strategies for sepsis
The document offers guidance on the four forms of fluid use; assessing whether intravenous fluid administration is indicated; and fluid therapy goals, timing, type, and other clinical parameters. The recommendations are based on a literature search that included 28 randomized clinical trials, 7 secondary analyses of RCTs, 20 observational studies, 5 systematic reviews or meta-analyses, 1 scoping review, 1 practice guideline, and 14 references from a reference review.
“Our review highlights that crystalloids should remain the standard of care for most critically ill patients, especially during early resuscitation,” Fernando G. Zampieri, MD, PhD, assistant adjunct professor of critical care medicine at the University of Alberta and Alberta Health Services, both in Edmonton, said in an interview. “In particular, starches should not be used in critically ill patients. Balanced solutions might be better for most patients, except for patients with traumatic brain injury, where 0.9% saline is recommended.”
The review was published online in JAMA.
Four therapeutic phases
Approximately 20%-30% of patients admitted to an intensive care unit have sepsis, and fluid therapy is a key component of their treatment. Although intravenous fluid can increase cardiac output and blood pressure, maintain or increase intravascular fluid volume, and deliver medications, too much fluid or the wrong type of fluid may cause harm.
“Deciding which type of fluid is the best for a patient [with sepsis] can be challenging,” said Dr. Zampieri.
Fluid therapy can be conceptualized as encompassing four overlapping phases from early illness through resolution of sepsis, according to the review. These phases include resuscitation (rapidly administering fluid to restore perfusion), optimization (assessing risks and benefits of additional fluids to treat shock and ensure organ perfusion), stabilization (using fluid therapy only when there is a signal of fluid responsiveness), and evacuation (eliminating excess fluid accumulated during treatment).
The review described the studies that underpin its key recommendations for management in these phases. Three RCTs included 3,723 patients with sepsis who received 1-2 L of fluid. They found that goal-directed therapy with administration of fluid boluses to attain a central venous pressure of 8-12 mm Hg, vasopressors to attain a mean arterial blood pressure of 65-90 mm Hg, and red blood cell transfusions or inotropes to attain a central venous oxygen saturation of at least 70% did not decrease mortality, compared with unstructured clinical care (24.9% vs. 25.4%, P = .68).
One RCT with 1,563 patients with sepsis and hypotension who received 1 L of fluid found that favoring vasopressor treatment did not improve mortality, compared with further fluid administration (14.0% vs. 14.9%, P = .61).
In another RCT, among 1,554 patients with septic shock who were treated in the ICU with at least 1 L of fluid, restricting fluid administration in the absence of severe hypoperfusion did not reduce mortality, compared with more liberal fluid administration (42.3% vs. 42.1%, P = .96).
An RCT of 1,000 patients with acute respiratory distress during the evacuation phase found that limiting fluid administration and giving diuretics improved the number of days alive without mechanical ventilation, compared with fluid treatment to attain higher intracardiac pressure (14.6 vs. 12.1 days, P < .001).
This study also found that hydroxyethyl starch significantly increased the incidence of kidney replacement therapy, compared with saline (7.0% vs. 5.8%, P = .04), Ringer lactate, or Ringer acetate.
Ultrasonography lacks validation
The authors summarized the key concerns about fluid therapy. Fluid therapy should be initiated for patients with evidence of sepsis-induced hypoperfusion who are likely to have increased cardiac output with fluid administration. Fluid administration should be discontinued when evidence of hypoperfusion resolves, the patient no longer responds to fluid, or the patient shows evidence of fluid overload.
Balanced solutions should be selected over 0.9% saline for fluid therapy, according to the review. Hydroxyethyl starches should not be used.
Fluid removal should be considered after the resuscitation and optimization phases and when a patient has stabilized, the authors wrote. Diuretics are first-line therapy to facilitate fluid elimination.
Kidney replacement therapy may be considered for patients with severe acute kidney injury who have complications from fluid overload and are unresponsive to diuretic therapy.
“The use of ultrasonography as a bedside tool to guide fluid resuscitation is promising but lacks validation in robust randomized controlled trials,” said Dr. Zampieri. “Point-of-care ultrasound may be useful to assess causes of shock and [helping to exclude] a life-threatening diagnosis at presentation, such as cardiac tamponade.”
Pending the emergence of further evidence, the authors suggest that clinicians prescribe fluids judiciously, preferably at aliquots followed by frequent reassessment. “Defining a resuscitation target (such as capillary refill time or lactate, among others) and performing fluid challenges to correct them while no overt signs of fluid overload (such as pulmonary edema) occur is a common practice that is also sustained by clinical research,” said Dr. Zampieri.
He added that the review’s recommendations are based on research conducted mainly in high-income settings, and that generalizability will depend on factors such as local standards of care and resource availability.
“Our review provides an overall guidance, but caution is warranted before extrapolating the suggestion to every possible clinical scenario,” he concluded.
Fluids as drugs
Commenting on the review, Hernando Gomez, MD, MPH, an associate professor of critical care medicine at the University of Pittsburgh, said: “I agree with the conclusions and commend the authors for this very practical revision of the literature.” Dr. Gomez was not involved in the review.
“I would like to stress the point, however, that although fluids can be harmful, particularly when not indicated and when used in excess, fluid resuscitation in patients with sepsis who have evidence of hypoperfusion is paramount,” he said.
“The association between fluid accumulation and poor outcomes is truly a Goldilocks problem, often described in the literature as a ‘U’ shape, where too little fluid (i.e., a very restrictive strategy) or too much fluid (i.e., use in excess and in discordance with the patient’s needs) can be harmful,” said Dr. Gomez.
Furthermore, every strategy to assess fluid responsiveness has limitations. “It is key that clinicians resist the temptation to dismiss these limitations, because decisions made on flawed data are as dangerous as not assessing fluid responsiveness in the first place,” he said.
Based on the evidence, clinicians should “think of fluids as a drug and carefully assess risks and benefits before deciding to administer fluids to their patients,” Dr. Gomez added. It is also important to separate the question “Does my patient need fluids?” from the question “Is my patient fluid responsive?”
“These are two different questions that often get conflated,” Dr. Gomez said. “If a bolus of fluid given to a patient who needs fluids and is fluid-responsive does not improve tissue perfusion, then fluids should not be given.”
No funding was reported for the review. Dr. Zampieri reported receiving fluids and logistics from Baxter Hospitalar during the conduct of the BaSICS trial, personal fees from Bactiguard for statistical consulting and from Baxter for participating in an advisory board, grants from Ionis Pharmaceuticals outside the submitted work, and serving as lead investigator of the BaSICS trial. Dr. Gomez reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The document offers guidance on the four forms of fluid use; assessing whether intravenous fluid administration is indicated; and fluid therapy goals, timing, type, and other clinical parameters. The recommendations are based on a literature search that included 28 randomized clinical trials, 7 secondary analyses of RCTs, 20 observational studies, 5 systematic reviews or meta-analyses, 1 scoping review, 1 practice guideline, and 14 references from a reference review.
“Our review highlights that crystalloids should remain the standard of care for most critically ill patients, especially during early resuscitation,” Fernando G. Zampieri, MD, PhD, assistant adjunct professor of critical care medicine at the University of Alberta and Alberta Health Services, both in Edmonton, said in an interview. “In particular, starches should not be used in critically ill patients. Balanced solutions might be better for most patients, except for patients with traumatic brain injury, where 0.9% saline is recommended.”
The review was published online in JAMA.
Four therapeutic phases
Approximately 20%-30% of patients admitted to an intensive care unit have sepsis, and fluid therapy is a key component of their treatment. Although intravenous fluid can increase cardiac output and blood pressure, maintain or increase intravascular fluid volume, and deliver medications, too much fluid or the wrong type of fluid may cause harm.
“Deciding which type of fluid is the best for a patient [with sepsis] can be challenging,” said Dr. Zampieri.
Fluid therapy can be conceptualized as encompassing four overlapping phases from early illness through resolution of sepsis, according to the review. These phases include resuscitation (rapidly administering fluid to restore perfusion), optimization (assessing risks and benefits of additional fluids to treat shock and ensure organ perfusion), stabilization (using fluid therapy only when there is a signal of fluid responsiveness), and evacuation (eliminating excess fluid accumulated during treatment).
The review described the studies that underpin its key recommendations for management in these phases. Three RCTs included 3,723 patients with sepsis who received 1-2 L of fluid. They found that goal-directed therapy with administration of fluid boluses to attain a central venous pressure of 8-12 mm Hg, vasopressors to attain a mean arterial blood pressure of 65-90 mm Hg, and red blood cell transfusions or inotropes to attain a central venous oxygen saturation of at least 70% did not decrease mortality, compared with unstructured clinical care (24.9% vs. 25.4%, P = .68).
One RCT with 1,563 patients with sepsis and hypotension who received 1 L of fluid found that favoring vasopressor treatment did not improve mortality, compared with further fluid administration (14.0% vs. 14.9%, P = .61).
In another RCT, among 1,554 patients with septic shock who were treated in the ICU with at least 1 L of fluid, restricting fluid administration in the absence of severe hypoperfusion did not reduce mortality, compared with more liberal fluid administration (42.3% vs. 42.1%, P = .96).
An RCT of 1,000 patients with acute respiratory distress during the evacuation phase found that limiting fluid administration and giving diuretics improved the number of days alive without mechanical ventilation, compared with fluid treatment to attain higher intracardiac pressure (14.6 vs. 12.1 days, P < .001).
This study also found that hydroxyethyl starch significantly increased the incidence of kidney replacement therapy, compared with saline (7.0% vs. 5.8%, P = .04), Ringer lactate, or Ringer acetate.
Ultrasonography lacks validation
The authors summarized the key concerns about fluid therapy. Fluid therapy should be initiated for patients with evidence of sepsis-induced hypoperfusion who are likely to have increased cardiac output with fluid administration. Fluid administration should be discontinued when evidence of hypoperfusion resolves, the patient no longer responds to fluid, or the patient shows evidence of fluid overload.
Balanced solutions should be selected over 0.9% saline for fluid therapy, according to the review. Hydroxyethyl starches should not be used.
Fluid removal should be considered after the resuscitation and optimization phases and when a patient has stabilized, the authors wrote. Diuretics are first-line therapy to facilitate fluid elimination.
Kidney replacement therapy may be considered for patients with severe acute kidney injury who have complications from fluid overload and are unresponsive to diuretic therapy.
“The use of ultrasonography as a bedside tool to guide fluid resuscitation is promising but lacks validation in robust randomized controlled trials,” said Dr. Zampieri. “Point-of-care ultrasound may be useful to assess causes of shock and [helping to exclude] a life-threatening diagnosis at presentation, such as cardiac tamponade.”
Pending the emergence of further evidence, the authors suggest that clinicians prescribe fluids judiciously, preferably at aliquots followed by frequent reassessment. “Defining a resuscitation target (such as capillary refill time or lactate, among others) and performing fluid challenges to correct them while no overt signs of fluid overload (such as pulmonary edema) occur is a common practice that is also sustained by clinical research,” said Dr. Zampieri.
He added that the review’s recommendations are based on research conducted mainly in high-income settings, and that generalizability will depend on factors such as local standards of care and resource availability.
“Our review provides an overall guidance, but caution is warranted before extrapolating the suggestion to every possible clinical scenario,” he concluded.
Fluids as drugs
Commenting on the review, Hernando Gomez, MD, MPH, an associate professor of critical care medicine at the University of Pittsburgh, said: “I agree with the conclusions and commend the authors for this very practical revision of the literature.” Dr. Gomez was not involved in the review.
“I would like to stress the point, however, that although fluids can be harmful, particularly when not indicated and when used in excess, fluid resuscitation in patients with sepsis who have evidence of hypoperfusion is paramount,” he said.
“The association between fluid accumulation and poor outcomes is truly a Goldilocks problem, often described in the literature as a ‘U’ shape, where too little fluid (i.e., a very restrictive strategy) or too much fluid (i.e., use in excess and in discordance with the patient’s needs) can be harmful,” said Dr. Gomez.
Furthermore, every strategy to assess fluid responsiveness has limitations. “It is key that clinicians resist the temptation to dismiss these limitations, because decisions made on flawed data are as dangerous as not assessing fluid responsiveness in the first place,” he said.
Based on the evidence, clinicians should “think of fluids as a drug and carefully assess risks and benefits before deciding to administer fluids to their patients,” Dr. Gomez added. It is also important to separate the question “Does my patient need fluids?” from the question “Is my patient fluid responsive?”
“These are two different questions that often get conflated,” Dr. Gomez said. “If a bolus of fluid given to a patient who needs fluids and is fluid-responsive does not improve tissue perfusion, then fluids should not be given.”
No funding was reported for the review. Dr. Zampieri reported receiving fluids and logistics from Baxter Hospitalar during the conduct of the BaSICS trial, personal fees from Bactiguard for statistical consulting and from Baxter for participating in an advisory board, grants from Ionis Pharmaceuticals outside the submitted work, and serving as lead investigator of the BaSICS trial. Dr. Gomez reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The document offers guidance on the four forms of fluid use; assessing whether intravenous fluid administration is indicated; and fluid therapy goals, timing, type, and other clinical parameters. The recommendations are based on a literature search that included 28 randomized clinical trials, 7 secondary analyses of RCTs, 20 observational studies, 5 systematic reviews or meta-analyses, 1 scoping review, 1 practice guideline, and 14 references from a reference review.
“Our review highlights that crystalloids should remain the standard of care for most critically ill patients, especially during early resuscitation,” Fernando G. Zampieri, MD, PhD, assistant adjunct professor of critical care medicine at the University of Alberta and Alberta Health Services, both in Edmonton, said in an interview. “In particular, starches should not be used in critically ill patients. Balanced solutions might be better for most patients, except for patients with traumatic brain injury, where 0.9% saline is recommended.”
The review was published online in JAMA.
Four therapeutic phases
Approximately 20%-30% of patients admitted to an intensive care unit have sepsis, and fluid therapy is a key component of their treatment. Although intravenous fluid can increase cardiac output and blood pressure, maintain or increase intravascular fluid volume, and deliver medications, too much fluid or the wrong type of fluid may cause harm.
“Deciding which type of fluid is the best for a patient [with sepsis] can be challenging,” said Dr. Zampieri.
Fluid therapy can be conceptualized as encompassing four overlapping phases from early illness through resolution of sepsis, according to the review. These phases include resuscitation (rapidly administering fluid to restore perfusion), optimization (assessing risks and benefits of additional fluids to treat shock and ensure organ perfusion), stabilization (using fluid therapy only when there is a signal of fluid responsiveness), and evacuation (eliminating excess fluid accumulated during treatment).
The review described the studies that underpin its key recommendations for management in these phases. Three RCTs included 3,723 patients with sepsis who received 1-2 L of fluid. They found that goal-directed therapy with administration of fluid boluses to attain a central venous pressure of 8-12 mm Hg, vasopressors to attain a mean arterial blood pressure of 65-90 mm Hg, and red blood cell transfusions or inotropes to attain a central venous oxygen saturation of at least 70% did not decrease mortality, compared with unstructured clinical care (24.9% vs. 25.4%, P = .68).
One RCT with 1,563 patients with sepsis and hypotension who received 1 L of fluid found that favoring vasopressor treatment did not improve mortality, compared with further fluid administration (14.0% vs. 14.9%, P = .61).
In another RCT, among 1,554 patients with septic shock who were treated in the ICU with at least 1 L of fluid, restricting fluid administration in the absence of severe hypoperfusion did not reduce mortality, compared with more liberal fluid administration (42.3% vs. 42.1%, P = .96).
An RCT of 1,000 patients with acute respiratory distress during the evacuation phase found that limiting fluid administration and giving diuretics improved the number of days alive without mechanical ventilation, compared with fluid treatment to attain higher intracardiac pressure (14.6 vs. 12.1 days, P < .001).
This study also found that hydroxyethyl starch significantly increased the incidence of kidney replacement therapy, compared with saline (7.0% vs. 5.8%, P = .04), Ringer lactate, or Ringer acetate.
Ultrasonography lacks validation
The authors summarized the key concerns about fluid therapy. Fluid therapy should be initiated for patients with evidence of sepsis-induced hypoperfusion who are likely to have increased cardiac output with fluid administration. Fluid administration should be discontinued when evidence of hypoperfusion resolves, the patient no longer responds to fluid, or the patient shows evidence of fluid overload.
Balanced solutions should be selected over 0.9% saline for fluid therapy, according to the review. Hydroxyethyl starches should not be used.
Fluid removal should be considered after the resuscitation and optimization phases and when a patient has stabilized, the authors wrote. Diuretics are first-line therapy to facilitate fluid elimination.
Kidney replacement therapy may be considered for patients with severe acute kidney injury who have complications from fluid overload and are unresponsive to diuretic therapy.
“The use of ultrasonography as a bedside tool to guide fluid resuscitation is promising but lacks validation in robust randomized controlled trials,” said Dr. Zampieri. “Point-of-care ultrasound may be useful to assess causes of shock and [helping to exclude] a life-threatening diagnosis at presentation, such as cardiac tamponade.”
Pending the emergence of further evidence, the authors suggest that clinicians prescribe fluids judiciously, preferably at aliquots followed by frequent reassessment. “Defining a resuscitation target (such as capillary refill time or lactate, among others) and performing fluid challenges to correct them while no overt signs of fluid overload (such as pulmonary edema) occur is a common practice that is also sustained by clinical research,” said Dr. Zampieri.
He added that the review’s recommendations are based on research conducted mainly in high-income settings, and that generalizability will depend on factors such as local standards of care and resource availability.
“Our review provides an overall guidance, but caution is warranted before extrapolating the suggestion to every possible clinical scenario,” he concluded.
Fluids as drugs
Commenting on the review, Hernando Gomez, MD, MPH, an associate professor of critical care medicine at the University of Pittsburgh, said: “I agree with the conclusions and commend the authors for this very practical revision of the literature.” Dr. Gomez was not involved in the review.
“I would like to stress the point, however, that although fluids can be harmful, particularly when not indicated and when used in excess, fluid resuscitation in patients with sepsis who have evidence of hypoperfusion is paramount,” he said.
“The association between fluid accumulation and poor outcomes is truly a Goldilocks problem, often described in the literature as a ‘U’ shape, where too little fluid (i.e., a very restrictive strategy) or too much fluid (i.e., use in excess and in discordance with the patient’s needs) can be harmful,” said Dr. Gomez.
Furthermore, every strategy to assess fluid responsiveness has limitations. “It is key that clinicians resist the temptation to dismiss these limitations, because decisions made on flawed data are as dangerous as not assessing fluid responsiveness in the first place,” he said.
Based on the evidence, clinicians should “think of fluids as a drug and carefully assess risks and benefits before deciding to administer fluids to their patients,” Dr. Gomez added. It is also important to separate the question “Does my patient need fluids?” from the question “Is my patient fluid responsive?”
“These are two different questions that often get conflated,” Dr. Gomez said. “If a bolus of fluid given to a patient who needs fluids and is fluid-responsive does not improve tissue perfusion, then fluids should not be given.”
No funding was reported for the review. Dr. Zampieri reported receiving fluids and logistics from Baxter Hospitalar during the conduct of the BaSICS trial, personal fees from Bactiguard for statistical consulting and from Baxter for participating in an advisory board, grants from Ionis Pharmaceuticals outside the submitted work, and serving as lead investigator of the BaSICS trial. Dr. Gomez reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA
Ticks use static electricity to latch onto hosts: Study
It turns out that some people really are tick magnets.
Researchers have discovered that ticks can defy gravity in their quest to latch onto people and animals. The key is static electricity, just like when someone rubs a balloon and things stick to it.
The study was published in the journal Current Biology. In the first phase of the research, scientists exposed ticks to furry rabbit feet and to acrylic surfaces that each had electrostatic charges.
“Ticks were readily attracted across air gaps of up to several millimeters or centimeters onto these statically charged surfaces,” the authors wrote.
In a second part of the study, the researchers created computer models simulating the electrostatic charges that exist in environments where both ticks and mammals are found. In one simulation, the researchers observed that the body parts of a cow with the most electric charge were the nose, tail, and legs, which are the body parts most likely to be encountered by a tick. They also found that the vegetation near the animal had a strong electric field that is just a few millimeters wide.
In a final phase of the study, the researchers conducted laboratory experiments in which they re-created the electric field conditions from the computer model and successfully lifted some ticks across an air gap, although some ticks did not make the full leap if they were observed to be resisting.
The authors noted that their findings could be applied to developing new tick prevention strategies, such as designing clothing that resists electrostatic charges or spraying livestock.
The study authors reported that they had no conflicts of interest.
A version of this article first appeared on WebMD.com.
It turns out that some people really are tick magnets.
Researchers have discovered that ticks can defy gravity in their quest to latch onto people and animals. The key is static electricity, just like when someone rubs a balloon and things stick to it.
The study was published in the journal Current Biology. In the first phase of the research, scientists exposed ticks to furry rabbit feet and to acrylic surfaces that each had electrostatic charges.
“Ticks were readily attracted across air gaps of up to several millimeters or centimeters onto these statically charged surfaces,” the authors wrote.
In a second part of the study, the researchers created computer models simulating the electrostatic charges that exist in environments where both ticks and mammals are found. In one simulation, the researchers observed that the body parts of a cow with the most electric charge were the nose, tail, and legs, which are the body parts most likely to be encountered by a tick. They also found that the vegetation near the animal had a strong electric field that is just a few millimeters wide.
In a final phase of the study, the researchers conducted laboratory experiments in which they re-created the electric field conditions from the computer model and successfully lifted some ticks across an air gap, although some ticks did not make the full leap if they were observed to be resisting.
The authors noted that their findings could be applied to developing new tick prevention strategies, such as designing clothing that resists electrostatic charges or spraying livestock.
The study authors reported that they had no conflicts of interest.
A version of this article first appeared on WebMD.com.
It turns out that some people really are tick magnets.
Researchers have discovered that ticks can defy gravity in their quest to latch onto people and animals. The key is static electricity, just like when someone rubs a balloon and things stick to it.
The study was published in the journal Current Biology. In the first phase of the research, scientists exposed ticks to furry rabbit feet and to acrylic surfaces that each had electrostatic charges.
“Ticks were readily attracted across air gaps of up to several millimeters or centimeters onto these statically charged surfaces,” the authors wrote.
In a second part of the study, the researchers created computer models simulating the electrostatic charges that exist in environments where both ticks and mammals are found. In one simulation, the researchers observed that the body parts of a cow with the most electric charge were the nose, tail, and legs, which are the body parts most likely to be encountered by a tick. They also found that the vegetation near the animal had a strong electric field that is just a few millimeters wide.
In a final phase of the study, the researchers conducted laboratory experiments in which they re-created the electric field conditions from the computer model and successfully lifted some ticks across an air gap, although some ticks did not make the full leap if they were observed to be resisting.
The authors noted that their findings could be applied to developing new tick prevention strategies, such as designing clothing that resists electrostatic charges or spraying livestock.
The study authors reported that they had no conflicts of interest.
A version of this article first appeared on WebMD.com.
FROM CURRENT BIOLOGY
FDA approves first leadless dual-chamber pacing system
already-approved leadless single-chamber device, Abbott has announced.
, one based in part on anThe company’s AVEIR DR leadless pacing system consists of two percutaneously implanted devices, the single-chamber AVEIR VR leadless pacemaker, implanted within the right ventricle, and the novel AVEIR AR single-chamber pacemaker for implantation in the right atrium.
The AVEIR DR system relies on proprietary wireless technology to provide bidirectional, beat-to-beat communication between its two components to achieve dual-chamber synchronization, the company stated in a press release on the approval.
The system also provides real-time pacing analysis, Abbott said, allowing clinicians to assess proper device placement during the procedure and before implantation. The system is designed to be easily removed if the patient’s pacing needs evolve or its battery needs replacing.
Experienced operators achieved a 98% implantation success rate using the AVIER DR system in a 300-patient study conducted at 55 sites in Canada, Europe, and the United States. In that study, 63% of the patients had sinus-node dysfunction and 33% had AV block as their primary dual-chamber pacing indication.
The system exceeded its predefined safety and performance goals, providing AV-synchronous pacing in 97% of patients for at least 3 months, it was reported in May at the annual scientific sessions of the Heart Rhythm Society and in a simultaneous publication in The New England Journal of Medicine.
“Modern medicine has been filled with technological achievements that fundamentally changed how doctors approach patient care, and now we can officially add dual-chamber leadless pacing to that list of achievements,” coauthor Vivek Reddy, MD, director of cardiac arrhythmia services for Mount Sinai Hospital and the Mount Sinai Health System, New York, said in the press release.
A version of this article first appeared on Medscape.com.
already-approved leadless single-chamber device, Abbott has announced.
, one based in part on anThe company’s AVEIR DR leadless pacing system consists of two percutaneously implanted devices, the single-chamber AVEIR VR leadless pacemaker, implanted within the right ventricle, and the novel AVEIR AR single-chamber pacemaker for implantation in the right atrium.
The AVEIR DR system relies on proprietary wireless technology to provide bidirectional, beat-to-beat communication between its two components to achieve dual-chamber synchronization, the company stated in a press release on the approval.
The system also provides real-time pacing analysis, Abbott said, allowing clinicians to assess proper device placement during the procedure and before implantation. The system is designed to be easily removed if the patient’s pacing needs evolve or its battery needs replacing.
Experienced operators achieved a 98% implantation success rate using the AVIER DR system in a 300-patient study conducted at 55 sites in Canada, Europe, and the United States. In that study, 63% of the patients had sinus-node dysfunction and 33% had AV block as their primary dual-chamber pacing indication.
The system exceeded its predefined safety and performance goals, providing AV-synchronous pacing in 97% of patients for at least 3 months, it was reported in May at the annual scientific sessions of the Heart Rhythm Society and in a simultaneous publication in The New England Journal of Medicine.
“Modern medicine has been filled with technological achievements that fundamentally changed how doctors approach patient care, and now we can officially add dual-chamber leadless pacing to that list of achievements,” coauthor Vivek Reddy, MD, director of cardiac arrhythmia services for Mount Sinai Hospital and the Mount Sinai Health System, New York, said in the press release.
A version of this article first appeared on Medscape.com.
already-approved leadless single-chamber device, Abbott has announced.
, one based in part on anThe company’s AVEIR DR leadless pacing system consists of two percutaneously implanted devices, the single-chamber AVEIR VR leadless pacemaker, implanted within the right ventricle, and the novel AVEIR AR single-chamber pacemaker for implantation in the right atrium.
The AVEIR DR system relies on proprietary wireless technology to provide bidirectional, beat-to-beat communication between its two components to achieve dual-chamber synchronization, the company stated in a press release on the approval.
The system also provides real-time pacing analysis, Abbott said, allowing clinicians to assess proper device placement during the procedure and before implantation. The system is designed to be easily removed if the patient’s pacing needs evolve or its battery needs replacing.
Experienced operators achieved a 98% implantation success rate using the AVIER DR system in a 300-patient study conducted at 55 sites in Canada, Europe, and the United States. In that study, 63% of the patients had sinus-node dysfunction and 33% had AV block as their primary dual-chamber pacing indication.
The system exceeded its predefined safety and performance goals, providing AV-synchronous pacing in 97% of patients for at least 3 months, it was reported in May at the annual scientific sessions of the Heart Rhythm Society and in a simultaneous publication in The New England Journal of Medicine.
“Modern medicine has been filled with technological achievements that fundamentally changed how doctors approach patient care, and now we can officially add dual-chamber leadless pacing to that list of achievements,” coauthor Vivek Reddy, MD, director of cardiac arrhythmia services for Mount Sinai Hospital and the Mount Sinai Health System, New York, said in the press release.
A version of this article first appeared on Medscape.com.
Malaria is spreading in the U.S. for the first time in 20 years
, the Centers for Disease Control and Prevention says.
The federal health agency recently issued a nationwide warning to health providers and officials to be on the lookout for symptoms of the potentially fatal illness. Usually, people in the U.S. who get malaria get the disease during international travel.
All five people – four in Florida and one in Texas – have received treatment and are improving, according to the CDC. The case in Texas is not related to the Florida cases, and all occurred in the past 2 months.
Malaria cannot be transmitted from person to person. It is spread by the bite of an infected female mosquito. The last cases of people being infected while in the U.S. occurred 20 years ago, when there were eight cases in Palm Beach County, Fla. The Texas Department of State Health Services said the last time malaria was locally acquired in the state was 1994.
The Florida Department of Health said it was spraying for mosquitoes in the two counties surrounding Sarasota, Fla., where the four cases occurred.
The CDC said the risk of getting malaria while in the United States “remains extremely low.” The agency advised people to protect themselves by taking precautions to prevent mosquito bites, such as wearing insect repellent and wearing long-sleeved shirts and pants. People should also do things to ensure that mosquitoes aren’t around their home, such as getting rid of standing water, which is an environment for mosquitoes to lay eggs.
More than 240 million malaria cases occur annually worldwide, the CDC said, with 95% in Africa. There are 2,000 cases diagnosed annually in the U.S. that are related to international travel. Malaria symptoms are similar to those of other illnesses and include fever, chills, a headache, and muscle aches. If not treated, malaria can be fatal.
A version of this article first appeared on WebMD.com.
, the Centers for Disease Control and Prevention says.
The federal health agency recently issued a nationwide warning to health providers and officials to be on the lookout for symptoms of the potentially fatal illness. Usually, people in the U.S. who get malaria get the disease during international travel.
All five people – four in Florida and one in Texas – have received treatment and are improving, according to the CDC. The case in Texas is not related to the Florida cases, and all occurred in the past 2 months.
Malaria cannot be transmitted from person to person. It is spread by the bite of an infected female mosquito. The last cases of people being infected while in the U.S. occurred 20 years ago, when there were eight cases in Palm Beach County, Fla. The Texas Department of State Health Services said the last time malaria was locally acquired in the state was 1994.
The Florida Department of Health said it was spraying for mosquitoes in the two counties surrounding Sarasota, Fla., where the four cases occurred.
The CDC said the risk of getting malaria while in the United States “remains extremely low.” The agency advised people to protect themselves by taking precautions to prevent mosquito bites, such as wearing insect repellent and wearing long-sleeved shirts and pants. People should also do things to ensure that mosquitoes aren’t around their home, such as getting rid of standing water, which is an environment for mosquitoes to lay eggs.
More than 240 million malaria cases occur annually worldwide, the CDC said, with 95% in Africa. There are 2,000 cases diagnosed annually in the U.S. that are related to international travel. Malaria symptoms are similar to those of other illnesses and include fever, chills, a headache, and muscle aches. If not treated, malaria can be fatal.
A version of this article first appeared on WebMD.com.
, the Centers for Disease Control and Prevention says.
The federal health agency recently issued a nationwide warning to health providers and officials to be on the lookout for symptoms of the potentially fatal illness. Usually, people in the U.S. who get malaria get the disease during international travel.
All five people – four in Florida and one in Texas – have received treatment and are improving, according to the CDC. The case in Texas is not related to the Florida cases, and all occurred in the past 2 months.
Malaria cannot be transmitted from person to person. It is spread by the bite of an infected female mosquito. The last cases of people being infected while in the U.S. occurred 20 years ago, when there were eight cases in Palm Beach County, Fla. The Texas Department of State Health Services said the last time malaria was locally acquired in the state was 1994.
The Florida Department of Health said it was spraying for mosquitoes in the two counties surrounding Sarasota, Fla., where the four cases occurred.
The CDC said the risk of getting malaria while in the United States “remains extremely low.” The agency advised people to protect themselves by taking precautions to prevent mosquito bites, such as wearing insect repellent and wearing long-sleeved shirts and pants. People should also do things to ensure that mosquitoes aren’t around their home, such as getting rid of standing water, which is an environment for mosquitoes to lay eggs.
More than 240 million malaria cases occur annually worldwide, the CDC said, with 95% in Africa. There are 2,000 cases diagnosed annually in the U.S. that are related to international travel. Malaria symptoms are similar to those of other illnesses and include fever, chills, a headache, and muscle aches. If not treated, malaria can be fatal.
A version of this article first appeared on WebMD.com.
Peripartum cardiomyopathy raises risks at future pregnancy despite LV recovery
, a new study suggests.
Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.
In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.
The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.
Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”
Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.
The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”
To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.
Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).
The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”
Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).
The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)
All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)
The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.
Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.
Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.
Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.
It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.
The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”
No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study suggests.
Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.
In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.
The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.
Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”
Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.
The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”
To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.
Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).
The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”
Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).
The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)
All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)
The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.
Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.
Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.
Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.
It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.
The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”
No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study suggests.
Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.
In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.
The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.
Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”
Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.
The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”
To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.
Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).
The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”
Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).
The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)
All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)
The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.
Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.
Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.
Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.
It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.
The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”
No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Postacute effects of COVID on par with those of sepsis, flu
A large observational study examined population-wide data for 13 postacute conditions in patients who had been hospitalized with a COVID-19 infection and found that all but one of these conditions, venous thromboembolism, occurred at comparable rates in those hospitalized for sepsis and influenza.
“For us, the main takeaway was that patients hospitalized for severe illness in general really require ongoing treatment and support after they’re discharged. That type of care is often very challenging to coordinate for people in a sometimes siloed and fragmented health care system,” study author Kieran Quinn, MD, PhD, a clinician at Sinai Health in Toronto, and assistant professor at the University of Toronto, said in an interview.
The study was published in JAMA Internal Medicine.
Postacute effects
The investigators compared clinical and health administrative data from 26,499 Ontarians hospitalized with COVID-19 with data from three additional cohorts who had been hospitalized with influenza (17,516 patients) and sepsis. The sepsis cohort was divided into two groups, those hospitalized during the COVID-19 pandemic (52,878 patients) and a historical control population (282,473 patients).
These comparators allowed the researchers to compare COVID-19 with other severe infectious illnesses and control for any changes in health care delivery that may have occurred during the pandemic. The addition of sepsis cohorts was needed for the latter purpose, since influenza rates dropped significantly after the onset of the pandemic.
The study outcomes (including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis) were selected based on previous associations with COVID-19 infections, as well as their availability in the data, according to Dr. Quinn. The investigators used diagnostic codes recorded in Ontario’s Institute for Clinical Evaluative Sciences database. The investigators observed some of the studied conditions in their own patients. “Many of us on the research team are practicing clinicians who care for people living with long COVID,” said Dr. Quinn.
Compared with cohorts with other serious infections, those hospitalized with COVID-19 were not at increased risk for selected cardiovascular or neurological disorders, rheumatoid arthritis, or mental health conditions within 1 year following hospitalization. Incident venous thromboembolic disease, however, was more common after hospitalization for COVID-19 than after hospitalization for influenza (adjusted hazard ratio, 1.77).
The study results corroborate previous findings that influenza and sepsis can have serious long-term health effects, such as heart failure, dementia, and depression, and found that the same was true for COVID-19 infections. For all three infections, patients at high risk require additional support after their initial discharge.
Defining long COVID
Although there was no increased risk with COVID-19 for most conditions, these results do not mean that the postacute effects of the infection, often called “long COVID,” are not significant, Dr. Quinn emphasized. The researcher believes that it’s important to listen to the many patients reporting symptoms and validate their experiences.
There needs to be greater consensus among the global health community on what constitutes long COVID. While the research led by Dr. Quinn focuses on postacute health conditions, some definitions of long COVID, such as that of the World Health Organization, refer only to ongoing symptoms of the original infection.
While there is now a diagnostic code for treating long COVID in Ontario, the data available to the researchers did not include information on some common symptoms of post-COVID condition, like chronic fatigue. In the data used, there was not an accurate way to identify patients who had developed conditions like myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome, said Dr. Quinn.
In addition to creating clear definitions and determining the best treatments, prevention is essential, said Dr. Quinn. Prior studies have shown that vaccination helps prevent ICU admission for COVID-19.
‘Important questions remain’
Commenting on the finding, Aravind Ganesh, MD, DPhil, a neurologist at the University of Calgary (Alta.), said that by including control populations, the study addressed an important limitation of previous research. Dr. Ganesh, who was not involved in the study, said that the controls help to determine the cause of associations found in other studies, including his own research on long-term symptoms following outpatient care for COVID-19.
“I think what this tells us is that maybe a lot of the issues that we’ve been seeing as complications attributable to COVID are, in fact, complications attributable to serious illness,” said Dr. Ganesh. He also found the association with venous thromboembolism interesting because the condition is recognized as a key risk factor for COVID-19 outcomes.
Compared with smaller randomized control trials, the population-level data provided a much larger sample size for the study. However, this design comes with limitations as well, Dr. Ganesh noted. The study relies on the administrative data of diagnostic codes and misses symptoms that aren’t associated with a diagnosis. In addition, because the cohorts were not assigned randomly, it may not account for preexisting risk factors.
While the study demonstrates associations with physical and mental health conditions, the cause of postacute effects from COVID-19, influenza, and sepsis is still unclear. “Important questions remain,” said Dr. Ganesh. “Why is it that these patients are experiencing these symptoms?”
The study was supported by ICES and the Canadian Institutes of Health Research. Dr. Quinn reported part-time employment at Public Health Ontario and stock in Pfizer and BioNTech. Dr. Ganesh reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large observational study examined population-wide data for 13 postacute conditions in patients who had been hospitalized with a COVID-19 infection and found that all but one of these conditions, venous thromboembolism, occurred at comparable rates in those hospitalized for sepsis and influenza.
“For us, the main takeaway was that patients hospitalized for severe illness in general really require ongoing treatment and support after they’re discharged. That type of care is often very challenging to coordinate for people in a sometimes siloed and fragmented health care system,” study author Kieran Quinn, MD, PhD, a clinician at Sinai Health in Toronto, and assistant professor at the University of Toronto, said in an interview.
The study was published in JAMA Internal Medicine.
Postacute effects
The investigators compared clinical and health administrative data from 26,499 Ontarians hospitalized with COVID-19 with data from three additional cohorts who had been hospitalized with influenza (17,516 patients) and sepsis. The sepsis cohort was divided into two groups, those hospitalized during the COVID-19 pandemic (52,878 patients) and a historical control population (282,473 patients).
These comparators allowed the researchers to compare COVID-19 with other severe infectious illnesses and control for any changes in health care delivery that may have occurred during the pandemic. The addition of sepsis cohorts was needed for the latter purpose, since influenza rates dropped significantly after the onset of the pandemic.
The study outcomes (including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis) were selected based on previous associations with COVID-19 infections, as well as their availability in the data, according to Dr. Quinn. The investigators used diagnostic codes recorded in Ontario’s Institute for Clinical Evaluative Sciences database. The investigators observed some of the studied conditions in their own patients. “Many of us on the research team are practicing clinicians who care for people living with long COVID,” said Dr. Quinn.
Compared with cohorts with other serious infections, those hospitalized with COVID-19 were not at increased risk for selected cardiovascular or neurological disorders, rheumatoid arthritis, or mental health conditions within 1 year following hospitalization. Incident venous thromboembolic disease, however, was more common after hospitalization for COVID-19 than after hospitalization for influenza (adjusted hazard ratio, 1.77).
The study results corroborate previous findings that influenza and sepsis can have serious long-term health effects, such as heart failure, dementia, and depression, and found that the same was true for COVID-19 infections. For all three infections, patients at high risk require additional support after their initial discharge.
Defining long COVID
Although there was no increased risk with COVID-19 for most conditions, these results do not mean that the postacute effects of the infection, often called “long COVID,” are not significant, Dr. Quinn emphasized. The researcher believes that it’s important to listen to the many patients reporting symptoms and validate their experiences.
There needs to be greater consensus among the global health community on what constitutes long COVID. While the research led by Dr. Quinn focuses on postacute health conditions, some definitions of long COVID, such as that of the World Health Organization, refer only to ongoing symptoms of the original infection.
While there is now a diagnostic code for treating long COVID in Ontario, the data available to the researchers did not include information on some common symptoms of post-COVID condition, like chronic fatigue. In the data used, there was not an accurate way to identify patients who had developed conditions like myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome, said Dr. Quinn.
In addition to creating clear definitions and determining the best treatments, prevention is essential, said Dr. Quinn. Prior studies have shown that vaccination helps prevent ICU admission for COVID-19.
‘Important questions remain’
Commenting on the finding, Aravind Ganesh, MD, DPhil, a neurologist at the University of Calgary (Alta.), said that by including control populations, the study addressed an important limitation of previous research. Dr. Ganesh, who was not involved in the study, said that the controls help to determine the cause of associations found in other studies, including his own research on long-term symptoms following outpatient care for COVID-19.
“I think what this tells us is that maybe a lot of the issues that we’ve been seeing as complications attributable to COVID are, in fact, complications attributable to serious illness,” said Dr. Ganesh. He also found the association with venous thromboembolism interesting because the condition is recognized as a key risk factor for COVID-19 outcomes.
Compared with smaller randomized control trials, the population-level data provided a much larger sample size for the study. However, this design comes with limitations as well, Dr. Ganesh noted. The study relies on the administrative data of diagnostic codes and misses symptoms that aren’t associated with a diagnosis. In addition, because the cohorts were not assigned randomly, it may not account for preexisting risk factors.
While the study demonstrates associations with physical and mental health conditions, the cause of postacute effects from COVID-19, influenza, and sepsis is still unclear. “Important questions remain,” said Dr. Ganesh. “Why is it that these patients are experiencing these symptoms?”
The study was supported by ICES and the Canadian Institutes of Health Research. Dr. Quinn reported part-time employment at Public Health Ontario and stock in Pfizer and BioNTech. Dr. Ganesh reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A large observational study examined population-wide data for 13 postacute conditions in patients who had been hospitalized with a COVID-19 infection and found that all but one of these conditions, venous thromboembolism, occurred at comparable rates in those hospitalized for sepsis and influenza.
“For us, the main takeaway was that patients hospitalized for severe illness in general really require ongoing treatment and support after they’re discharged. That type of care is often very challenging to coordinate for people in a sometimes siloed and fragmented health care system,” study author Kieran Quinn, MD, PhD, a clinician at Sinai Health in Toronto, and assistant professor at the University of Toronto, said in an interview.
The study was published in JAMA Internal Medicine.
Postacute effects
The investigators compared clinical and health administrative data from 26,499 Ontarians hospitalized with COVID-19 with data from three additional cohorts who had been hospitalized with influenza (17,516 patients) and sepsis. The sepsis cohort was divided into two groups, those hospitalized during the COVID-19 pandemic (52,878 patients) and a historical control population (282,473 patients).
These comparators allowed the researchers to compare COVID-19 with other severe infectious illnesses and control for any changes in health care delivery that may have occurred during the pandemic. The addition of sepsis cohorts was needed for the latter purpose, since influenza rates dropped significantly after the onset of the pandemic.
The study outcomes (including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis) were selected based on previous associations with COVID-19 infections, as well as their availability in the data, according to Dr. Quinn. The investigators used diagnostic codes recorded in Ontario’s Institute for Clinical Evaluative Sciences database. The investigators observed some of the studied conditions in their own patients. “Many of us on the research team are practicing clinicians who care for people living with long COVID,” said Dr. Quinn.
Compared with cohorts with other serious infections, those hospitalized with COVID-19 were not at increased risk for selected cardiovascular or neurological disorders, rheumatoid arthritis, or mental health conditions within 1 year following hospitalization. Incident venous thromboembolic disease, however, was more common after hospitalization for COVID-19 than after hospitalization for influenza (adjusted hazard ratio, 1.77).
The study results corroborate previous findings that influenza and sepsis can have serious long-term health effects, such as heart failure, dementia, and depression, and found that the same was true for COVID-19 infections. For all three infections, patients at high risk require additional support after their initial discharge.
Defining long COVID
Although there was no increased risk with COVID-19 for most conditions, these results do not mean that the postacute effects of the infection, often called “long COVID,” are not significant, Dr. Quinn emphasized. The researcher believes that it’s important to listen to the many patients reporting symptoms and validate their experiences.
There needs to be greater consensus among the global health community on what constitutes long COVID. While the research led by Dr. Quinn focuses on postacute health conditions, some definitions of long COVID, such as that of the World Health Organization, refer only to ongoing symptoms of the original infection.
While there is now a diagnostic code for treating long COVID in Ontario, the data available to the researchers did not include information on some common symptoms of post-COVID condition, like chronic fatigue. In the data used, there was not an accurate way to identify patients who had developed conditions like myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome, said Dr. Quinn.
In addition to creating clear definitions and determining the best treatments, prevention is essential, said Dr. Quinn. Prior studies have shown that vaccination helps prevent ICU admission for COVID-19.
‘Important questions remain’
Commenting on the finding, Aravind Ganesh, MD, DPhil, a neurologist at the University of Calgary (Alta.), said that by including control populations, the study addressed an important limitation of previous research. Dr. Ganesh, who was not involved in the study, said that the controls help to determine the cause of associations found in other studies, including his own research on long-term symptoms following outpatient care for COVID-19.
“I think what this tells us is that maybe a lot of the issues that we’ve been seeing as complications attributable to COVID are, in fact, complications attributable to serious illness,” said Dr. Ganesh. He also found the association with venous thromboembolism interesting because the condition is recognized as a key risk factor for COVID-19 outcomes.
Compared with smaller randomized control trials, the population-level data provided a much larger sample size for the study. However, this design comes with limitations as well, Dr. Ganesh noted. The study relies on the administrative data of diagnostic codes and misses symptoms that aren’t associated with a diagnosis. In addition, because the cohorts were not assigned randomly, it may not account for preexisting risk factors.
While the study demonstrates associations with physical and mental health conditions, the cause of postacute effects from COVID-19, influenza, and sepsis is still unclear. “Important questions remain,” said Dr. Ganesh. “Why is it that these patients are experiencing these symptoms?”
The study was supported by ICES and the Canadian Institutes of Health Research. Dr. Quinn reported part-time employment at Public Health Ontario and stock in Pfizer and BioNTech. Dr. Ganesh reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA INTERNAL MEDICINE
New ESH hypertension guidelines aim for simplified message
The guidelines, which are endorsed by the European Renal Association and the International Society of Hypertension, were presented during the annual European Meeting on Hypertension and Cardiovascular Protection Meeting in Milan, Italy.
The guidelines consensus document was also published online in the Journal of Hypertension. Giuseppe Mancia, MD, professor emeritus of medicine, University Milano-Bicocca, Italy, and Reinhold Kreutz, MD, PhD, Charité–University Medicine Berlin, were cochairs of the task force that created the document.
“We have tried to provide a simplified message to key topics with these new guidelines,” Dr. Kreutz said in an interview.
“We have confirmed the definition of hypertension and provide clear guidance for blood pressure monitoring and a simplified general strategy targeting similar blood pressure goals for most patients, although the treatment algorithms of how you get there may be different for different patient groups.”
Dr. Kreutz added: “Because hypertension is so prevalent and many patients have comorbidities, it is not easy to have one approach for all, but we have tried to simplify the key messages as much as possible, with a target that is more general to the whole population.”
While there are no major surprises in the guidelines, there are multiple advances and added-value changes, including clear advice on how to measure blood pressure, an upgrade for beta-blockers in the treatment algorithms, and a new definition and treatment recommendations for “true resistant hypertension.”
Definition remains unchanged
The definition of hypertension remains unchanged from the previous guidelines – repeated office systolic blood pressure values of ≥ 140 mm Hg and/or diastolic blood pressure values of ≥ 90 mm Hg.
“The definition and classification of hypertension has not changed in these new guidelines,” Dr. Kreutz said. “While there have been suggestions that the definition/target should be changed again, particularly about blood pressure lowering being beneficial at the very low pressure range, after reviewing all the evidence we do not agree with this, and we are standing with the definition of hypertension when intervention is beneficial rather than doing nothing or causing harm.”
Clear guidance on measurement
Dr. Kreutz points out that the correct measurement of blood pressure is of key importance, and the new guidelines include a detailed algorithm on how to measure blood pressure. The preferred method is automated cuff-based blood pressure measurement.
“There are still many variations in blood pressure measurement in clinical practice, so we now have clear guidance on how to measure blood pressure in the office but also at home,” he commented.
They have upgraded the use of out-of-office blood pressure measurement, particularly home measurement, as useful in long-term management. “In future, there should be more emphasis on follow-up using technology with remote control and virtual care.”
Thresholds for starting treatment
On thresholds for initiating antihypertensive therapy, the guidelines recommend that treatment be initiated for most patients when systolic blood pressure is ≥ 140 mm Hg or diastolic blood pressure is ≥ 90 mm Hg.
The same recommendation is given for patients with grade 1 hypertension (systolic, 140-159 mm Hg; and/or diastolic, 90-99 mm Hg) irrespective of cardiovascular risk, although they add that for patients in the lower blood pressure range who have no hypertension-mediated organ damage and who are at low cardiovascular risk, consideration may be given to starting treatment with lifestyle changes only. If, however, blood pressure control is not achieved within a few months of a lifestyle-based approach alone, drug treatment is necessary.
For older patients (aged 80 or older), the task force recommends initiation of drug treatment at 160 mm Hg systolic, although a lower systolic threshold of 140-160 mm Hg may be considered. The authors note that thresholds for the initiation of drug treatment for very frail patients should be individualized.
Blood pressure targets
In the new guidelines, the blood pressure target is the same as in the previous guidelines for the general population of patients with hypertension. The goal is < 140/80 mm Hg for most patients. This accounts for the major portion of the protective effect of blood pressure lowering.
However, the consensus document notes that despite the smaller incremental benefit, an effort should be made to reach a range of 120-129/70-79 mm Hg, but only if treatment is well tolerated to avoid the risk of treatment discontinuation because of adverse events, which might offset, in part or completely, the incremental reduction in cardiovascular outcomes.
Elaborating on this, Dr. Kreutz said, “We should aim for the systolic blood pressure to be within the range of below 140 mm Hg down to 120 mm Hg, with a specific target of around 130 mm Hg for most patients and lower in patients in whom drug treatments are well tolerated and who are at high risk.
“The problem is, if we go for a target of lower that 130 mm Hg, the evidence gets weaker, the benefits diminish, and we risk losing patients because of adverse effects from using so many drugs,” he added. “But in younger and fitter patients, we would recommend the lower the better, but not below 120 mm Hg.”
Dr. Kreutz noted that the new guidelines have tried to simplify recommendations on target pressures. “We have tried to simplify guidance to focus on a target of around 130 for almost all patients. Before, it wasn’t so clear. There were different targets for different groups of patients with various comorbidities or older patients. But now we are saying the range of 120 to 139 is suitable for the vast majority of patients.”
The guidelines do allow slightly higher targets for older and very frail patients.
Drug treatments
The guidelines advise that blood pressure lowering be prioritized over the selection of specific antihypertensive drug classes. The use of any of the five major drug classes – angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium blockers, and thiazide/thiazidelike diuretics – and their combinations are recommended as the basis of antihypertensive treatment strategies.
They advise starting with a two-drug combination for most patients. The preferred combinations including a renin-angiotensin blocker (either an ACE inhibitor or an ARB) with a calcium blocker or a thiazide/thiazidelike diuretic, preferably in a single-pill combination to reduce pill burden and improve adherence and outcome.
If blood pressure is not controlled with the initial two-drug combination at the maximum recommended and tolerated dose of the respective components, treatment should be increased to a three-drug combination.
“We can control 60% of patients in the general hypertensive population with dual therapy, and up to 90% with triple therapy,” Dr. Kreutz said. “Only a small percentage need a fourth drug.”
A new feature of the guidelines is the upgrading of beta-blockers in the treatment algorithms.
“Beta-blockers may not have previously been considered as a first choice of antihypertensive medication, but we see that in clinical practice, many patients are actually treated with these drugs because there are so many conditions in which beta-blockers have a compelling evidence-based indication or are believed to be favorable,” he said. “So, we are now positioning beta-blockers as drugs that can be used at any step of the treatment algorithm if there is a guideline directed indication or other conditions for which they are thought to be beneficial.”
The guidelines also recommend that all drugs be given as once-daily preparations and that they be taken preferably in the morning.
“The new TIME study has established that there is no difference in outcome with morning or evening dosing, but we know that adherence is often better when drugs are taken in the morning, and it is not advisable to take diuretics in the evening,” Dr. Kreutz said.
‘True resistant hypertension’
The guidelines have introduced a new term, “true resistant hypertension,” defined as systolic blood pressure of ≥ 140 mm Hg or diastolic blood pressure of ≥ 90 mm Hg in the presence of the following conditions: the maximum recommended and tolerated doses of a three-drug combination comprising a renin-angiotensin system blocker (either an ACE inhibitor or an ARB), a calcium blocker, and a thiazide/thiazidelike diuretic were used; inadequate blood pressure control has been confirmed by ambulatory (preferable) or home blood pressure measurement; and various causes of pseudo-resistant hypertension (especially poor medication adherence) and secondary hypertension have been excluded.
“There are many patients who may appear to have resistant hypertension, but we need to screen them carefully to ensure they are adherent to treatment, and then most of these patients are found not to be truly resistant,” Dr. Kreutz explained. “We estimate that only about 5% of patients have true resistant hypertension.”
For these patients with true resistant hypertension, two treatment approaches are recommended.
For those who do not have advanced kidney disease (glomerular filtration rate > 40 mL/min), renal denervation can be considered. This is a new II B recommendation.
Dr. Kreutz noted that studies of renal denervation excluded patients with advanced kidney disease, so there are no data for this group. For these patients, the guidelines suggest that a combination diuretic approach (chlorthalidone with a loop diuretic) could be considered in light of the results of the recent CLICK study.
Differences from U.S. guidelines?
Commenting on the new European guidelines for this news organization, Paul Whelton, MD, chair of the most recent American College of Cardiology/American Heart Association hypertension guidelines committee, said: “Publication of these guidelines is important. I congratulate the European task force. It is an enormous amount of time and effort.”
Dr. Whelton, who is Show Chwan Chair in Global Public Health at Tulane University, New Orleans, and president of the World Hypertension League, added: “I would say the changes are incremental rather than major, but that is probably appropriate.”
He welcomed the greater emphasis on out-of-office blood pressure measurement, saying, “That’s where we should be headed.”
Asked how the European guidelines differ from the U.S. guidelines, Dr. Whelton commented: “There are differences, but they are not huge. The major hypertension guidelines across the world are much more alike than they are different.”
He pointed out that both the U.S. and European guidelines aim for a target blood pressure of 130/80 mm Hg for most patients but have different ways of issuing that advice.
“The Europeans recommend a minimum goal of 140/90 mm Hg, and if there are no issues, then press on to get to under 130/80 mm Hg. That’s kind of a two-step process,” he said. “In the U.S., we’ve gone for a more direct approach of just recommending less than 130/80 mm Hg.
“My fear with the European approach is that by saying, get to 140/90 mm Hg first, then move on to 130/80 mm Hg, is that you’re likely to lose people. And doctors could feel that 140/90 is fine.”
More effort needed on implementation
Dr. Whelton says that where all hypertension guidelines are lacking is in the implementation of the recommendations.
“We are all falling down on implementation,” he said. “We have a huge burden of illness, and it is a very cost-effective area for management, but still, rates of blood pressure control are very bad. Generally speaking, even with a very conservative target of 140/90, the best countries only have control rates of around 30%, and this can be as low as 8% in some low/middle-income countries.”
Dr. Whelton believes the approach to blood pressure management needs to change.
“We know that the current traditional model of care, where blood pressure is managed by your local doctor, is not working. It is hopeless,” he said. “That is not an indictment of these doctors. It’s just that they have more pressing issues to deal with, so we need to look at other models.”
He suggests that the way forward is through convenient, community-based care delivered by a team in which nonphysicians assist in much of the management and in which reliable, affordable medications are given at the point of care, with patients tracked with electronic health records so as to identify those who are not adhering to their medication regimens.
“We know that using simple protocols will work for the vast majority of people. We don’t need to individualize or complicate this too much. That tends to lose people in the process.”
Dr. Whelton makes the point that it is well known how to diagnose and treat hypertension, yet this is not being done well.
“We are doing these things really badly. In routine care, blood pressure is measured horribly. Nobody would accept a pilot of a plane saying he should be doing all these procedures but he’s too busy and it’s probably okay, but that’s the way blood pressure is often measured in clinical practice,” he added. “And we can’t really do a good job if were not measuring the key variable properly that the diagnosis is based on.”
Dr. Whelton also points out that the medical profession is not making enough effort to have patients reach target levels.
“If you’re in a country where very few people are being treated and very high pressures are common, then of course you have to focus on that group first. But in most of the Western world, we are long past that, so we can move on down the chain. We then get to a lot more people with moderately high blood pressure getting exposed to increases in risk, and while this is not quite as dramatic as those with very high pressures at the individual risk level, because there are so many of them, that’s where a lot of events are occurring,” he says.
“If we get everyone to 140/90 mm Hg, we can probably prevent 60% of blood pressure–related events. But if we can get them all down to 130 mm Hg systolic, then we can prevent 75%-80% of events. It’s often quite easy to get to that target, but patients need help and encouragement.”
Going forward, he concluded, guidelines should pivot to focus more on implementation.
“We all try to make the guidelines as approachable as possible, but they are encyclopedic, and many doctors just continue doing what they are doing. That is our big challenge.”
A version of this article first appeared on Medscape.com.
The guidelines, which are endorsed by the European Renal Association and the International Society of Hypertension, were presented during the annual European Meeting on Hypertension and Cardiovascular Protection Meeting in Milan, Italy.
The guidelines consensus document was also published online in the Journal of Hypertension. Giuseppe Mancia, MD, professor emeritus of medicine, University Milano-Bicocca, Italy, and Reinhold Kreutz, MD, PhD, Charité–University Medicine Berlin, were cochairs of the task force that created the document.
“We have tried to provide a simplified message to key topics with these new guidelines,” Dr. Kreutz said in an interview.
“We have confirmed the definition of hypertension and provide clear guidance for blood pressure monitoring and a simplified general strategy targeting similar blood pressure goals for most patients, although the treatment algorithms of how you get there may be different for different patient groups.”
Dr. Kreutz added: “Because hypertension is so prevalent and many patients have comorbidities, it is not easy to have one approach for all, but we have tried to simplify the key messages as much as possible, with a target that is more general to the whole population.”
While there are no major surprises in the guidelines, there are multiple advances and added-value changes, including clear advice on how to measure blood pressure, an upgrade for beta-blockers in the treatment algorithms, and a new definition and treatment recommendations for “true resistant hypertension.”
Definition remains unchanged
The definition of hypertension remains unchanged from the previous guidelines – repeated office systolic blood pressure values of ≥ 140 mm Hg and/or diastolic blood pressure values of ≥ 90 mm Hg.
“The definition and classification of hypertension has not changed in these new guidelines,” Dr. Kreutz said. “While there have been suggestions that the definition/target should be changed again, particularly about blood pressure lowering being beneficial at the very low pressure range, after reviewing all the evidence we do not agree with this, and we are standing with the definition of hypertension when intervention is beneficial rather than doing nothing or causing harm.”
Clear guidance on measurement
Dr. Kreutz points out that the correct measurement of blood pressure is of key importance, and the new guidelines include a detailed algorithm on how to measure blood pressure. The preferred method is automated cuff-based blood pressure measurement.
“There are still many variations in blood pressure measurement in clinical practice, so we now have clear guidance on how to measure blood pressure in the office but also at home,” he commented.
They have upgraded the use of out-of-office blood pressure measurement, particularly home measurement, as useful in long-term management. “In future, there should be more emphasis on follow-up using technology with remote control and virtual care.”
Thresholds for starting treatment
On thresholds for initiating antihypertensive therapy, the guidelines recommend that treatment be initiated for most patients when systolic blood pressure is ≥ 140 mm Hg or diastolic blood pressure is ≥ 90 mm Hg.
The same recommendation is given for patients with grade 1 hypertension (systolic, 140-159 mm Hg; and/or diastolic, 90-99 mm Hg) irrespective of cardiovascular risk, although they add that for patients in the lower blood pressure range who have no hypertension-mediated organ damage and who are at low cardiovascular risk, consideration may be given to starting treatment with lifestyle changes only. If, however, blood pressure control is not achieved within a few months of a lifestyle-based approach alone, drug treatment is necessary.
For older patients (aged 80 or older), the task force recommends initiation of drug treatment at 160 mm Hg systolic, although a lower systolic threshold of 140-160 mm Hg may be considered. The authors note that thresholds for the initiation of drug treatment for very frail patients should be individualized.
Blood pressure targets
In the new guidelines, the blood pressure target is the same as in the previous guidelines for the general population of patients with hypertension. The goal is < 140/80 mm Hg for most patients. This accounts for the major portion of the protective effect of blood pressure lowering.
However, the consensus document notes that despite the smaller incremental benefit, an effort should be made to reach a range of 120-129/70-79 mm Hg, but only if treatment is well tolerated to avoid the risk of treatment discontinuation because of adverse events, which might offset, in part or completely, the incremental reduction in cardiovascular outcomes.
Elaborating on this, Dr. Kreutz said, “We should aim for the systolic blood pressure to be within the range of below 140 mm Hg down to 120 mm Hg, with a specific target of around 130 mm Hg for most patients and lower in patients in whom drug treatments are well tolerated and who are at high risk.
“The problem is, if we go for a target of lower that 130 mm Hg, the evidence gets weaker, the benefits diminish, and we risk losing patients because of adverse effects from using so many drugs,” he added. “But in younger and fitter patients, we would recommend the lower the better, but not below 120 mm Hg.”
Dr. Kreutz noted that the new guidelines have tried to simplify recommendations on target pressures. “We have tried to simplify guidance to focus on a target of around 130 for almost all patients. Before, it wasn’t so clear. There were different targets for different groups of patients with various comorbidities or older patients. But now we are saying the range of 120 to 139 is suitable for the vast majority of patients.”
The guidelines do allow slightly higher targets for older and very frail patients.
Drug treatments
The guidelines advise that blood pressure lowering be prioritized over the selection of specific antihypertensive drug classes. The use of any of the five major drug classes – angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium blockers, and thiazide/thiazidelike diuretics – and their combinations are recommended as the basis of antihypertensive treatment strategies.
They advise starting with a two-drug combination for most patients. The preferred combinations including a renin-angiotensin blocker (either an ACE inhibitor or an ARB) with a calcium blocker or a thiazide/thiazidelike diuretic, preferably in a single-pill combination to reduce pill burden and improve adherence and outcome.
If blood pressure is not controlled with the initial two-drug combination at the maximum recommended and tolerated dose of the respective components, treatment should be increased to a three-drug combination.
“We can control 60% of patients in the general hypertensive population with dual therapy, and up to 90% with triple therapy,” Dr. Kreutz said. “Only a small percentage need a fourth drug.”
A new feature of the guidelines is the upgrading of beta-blockers in the treatment algorithms.
“Beta-blockers may not have previously been considered as a first choice of antihypertensive medication, but we see that in clinical practice, many patients are actually treated with these drugs because there are so many conditions in which beta-blockers have a compelling evidence-based indication or are believed to be favorable,” he said. “So, we are now positioning beta-blockers as drugs that can be used at any step of the treatment algorithm if there is a guideline directed indication or other conditions for which they are thought to be beneficial.”
The guidelines also recommend that all drugs be given as once-daily preparations and that they be taken preferably in the morning.
“The new TIME study has established that there is no difference in outcome with morning or evening dosing, but we know that adherence is often better when drugs are taken in the morning, and it is not advisable to take diuretics in the evening,” Dr. Kreutz said.
‘True resistant hypertension’
The guidelines have introduced a new term, “true resistant hypertension,” defined as systolic blood pressure of ≥ 140 mm Hg or diastolic blood pressure of ≥ 90 mm Hg in the presence of the following conditions: the maximum recommended and tolerated doses of a three-drug combination comprising a renin-angiotensin system blocker (either an ACE inhibitor or an ARB), a calcium blocker, and a thiazide/thiazidelike diuretic were used; inadequate blood pressure control has been confirmed by ambulatory (preferable) or home blood pressure measurement; and various causes of pseudo-resistant hypertension (especially poor medication adherence) and secondary hypertension have been excluded.
“There are many patients who may appear to have resistant hypertension, but we need to screen them carefully to ensure they are adherent to treatment, and then most of these patients are found not to be truly resistant,” Dr. Kreutz explained. “We estimate that only about 5% of patients have true resistant hypertension.”
For these patients with true resistant hypertension, two treatment approaches are recommended.
For those who do not have advanced kidney disease (glomerular filtration rate > 40 mL/min), renal denervation can be considered. This is a new II B recommendation.
Dr. Kreutz noted that studies of renal denervation excluded patients with advanced kidney disease, so there are no data for this group. For these patients, the guidelines suggest that a combination diuretic approach (chlorthalidone with a loop diuretic) could be considered in light of the results of the recent CLICK study.
Differences from U.S. guidelines?
Commenting on the new European guidelines for this news organization, Paul Whelton, MD, chair of the most recent American College of Cardiology/American Heart Association hypertension guidelines committee, said: “Publication of these guidelines is important. I congratulate the European task force. It is an enormous amount of time and effort.”
Dr. Whelton, who is Show Chwan Chair in Global Public Health at Tulane University, New Orleans, and president of the World Hypertension League, added: “I would say the changes are incremental rather than major, but that is probably appropriate.”
He welcomed the greater emphasis on out-of-office blood pressure measurement, saying, “That’s where we should be headed.”
Asked how the European guidelines differ from the U.S. guidelines, Dr. Whelton commented: “There are differences, but they are not huge. The major hypertension guidelines across the world are much more alike than they are different.”
He pointed out that both the U.S. and European guidelines aim for a target blood pressure of 130/80 mm Hg for most patients but have different ways of issuing that advice.
“The Europeans recommend a minimum goal of 140/90 mm Hg, and if there are no issues, then press on to get to under 130/80 mm Hg. That’s kind of a two-step process,” he said. “In the U.S., we’ve gone for a more direct approach of just recommending less than 130/80 mm Hg.
“My fear with the European approach is that by saying, get to 140/90 mm Hg first, then move on to 130/80 mm Hg, is that you’re likely to lose people. And doctors could feel that 140/90 is fine.”
More effort needed on implementation
Dr. Whelton says that where all hypertension guidelines are lacking is in the implementation of the recommendations.
“We are all falling down on implementation,” he said. “We have a huge burden of illness, and it is a very cost-effective area for management, but still, rates of blood pressure control are very bad. Generally speaking, even with a very conservative target of 140/90, the best countries only have control rates of around 30%, and this can be as low as 8% in some low/middle-income countries.”
Dr. Whelton believes the approach to blood pressure management needs to change.
“We know that the current traditional model of care, where blood pressure is managed by your local doctor, is not working. It is hopeless,” he said. “That is not an indictment of these doctors. It’s just that they have more pressing issues to deal with, so we need to look at other models.”
He suggests that the way forward is through convenient, community-based care delivered by a team in which nonphysicians assist in much of the management and in which reliable, affordable medications are given at the point of care, with patients tracked with electronic health records so as to identify those who are not adhering to their medication regimens.
“We know that using simple protocols will work for the vast majority of people. We don’t need to individualize or complicate this too much. That tends to lose people in the process.”
Dr. Whelton makes the point that it is well known how to diagnose and treat hypertension, yet this is not being done well.
“We are doing these things really badly. In routine care, blood pressure is measured horribly. Nobody would accept a pilot of a plane saying he should be doing all these procedures but he’s too busy and it’s probably okay, but that’s the way blood pressure is often measured in clinical practice,” he added. “And we can’t really do a good job if were not measuring the key variable properly that the diagnosis is based on.”
Dr. Whelton also points out that the medical profession is not making enough effort to have patients reach target levels.
“If you’re in a country where very few people are being treated and very high pressures are common, then of course you have to focus on that group first. But in most of the Western world, we are long past that, so we can move on down the chain. We then get to a lot more people with moderately high blood pressure getting exposed to increases in risk, and while this is not quite as dramatic as those with very high pressures at the individual risk level, because there are so many of them, that’s where a lot of events are occurring,” he says.
“If we get everyone to 140/90 mm Hg, we can probably prevent 60% of blood pressure–related events. But if we can get them all down to 130 mm Hg systolic, then we can prevent 75%-80% of events. It’s often quite easy to get to that target, but patients need help and encouragement.”
Going forward, he concluded, guidelines should pivot to focus more on implementation.
“We all try to make the guidelines as approachable as possible, but they are encyclopedic, and many doctors just continue doing what they are doing. That is our big challenge.”
A version of this article first appeared on Medscape.com.
The guidelines, which are endorsed by the European Renal Association and the International Society of Hypertension, were presented during the annual European Meeting on Hypertension and Cardiovascular Protection Meeting in Milan, Italy.
The guidelines consensus document was also published online in the Journal of Hypertension. Giuseppe Mancia, MD, professor emeritus of medicine, University Milano-Bicocca, Italy, and Reinhold Kreutz, MD, PhD, Charité–University Medicine Berlin, were cochairs of the task force that created the document.
“We have tried to provide a simplified message to key topics with these new guidelines,” Dr. Kreutz said in an interview.
“We have confirmed the definition of hypertension and provide clear guidance for blood pressure monitoring and a simplified general strategy targeting similar blood pressure goals for most patients, although the treatment algorithms of how you get there may be different for different patient groups.”
Dr. Kreutz added: “Because hypertension is so prevalent and many patients have comorbidities, it is not easy to have one approach for all, but we have tried to simplify the key messages as much as possible, with a target that is more general to the whole population.”
While there are no major surprises in the guidelines, there are multiple advances and added-value changes, including clear advice on how to measure blood pressure, an upgrade for beta-blockers in the treatment algorithms, and a new definition and treatment recommendations for “true resistant hypertension.”
Definition remains unchanged
The definition of hypertension remains unchanged from the previous guidelines – repeated office systolic blood pressure values of ≥ 140 mm Hg and/or diastolic blood pressure values of ≥ 90 mm Hg.
“The definition and classification of hypertension has not changed in these new guidelines,” Dr. Kreutz said. “While there have been suggestions that the definition/target should be changed again, particularly about blood pressure lowering being beneficial at the very low pressure range, after reviewing all the evidence we do not agree with this, and we are standing with the definition of hypertension when intervention is beneficial rather than doing nothing or causing harm.”
Clear guidance on measurement
Dr. Kreutz points out that the correct measurement of blood pressure is of key importance, and the new guidelines include a detailed algorithm on how to measure blood pressure. The preferred method is automated cuff-based blood pressure measurement.
“There are still many variations in blood pressure measurement in clinical practice, so we now have clear guidance on how to measure blood pressure in the office but also at home,” he commented.
They have upgraded the use of out-of-office blood pressure measurement, particularly home measurement, as useful in long-term management. “In future, there should be more emphasis on follow-up using technology with remote control and virtual care.”
Thresholds for starting treatment
On thresholds for initiating antihypertensive therapy, the guidelines recommend that treatment be initiated for most patients when systolic blood pressure is ≥ 140 mm Hg or diastolic blood pressure is ≥ 90 mm Hg.
The same recommendation is given for patients with grade 1 hypertension (systolic, 140-159 mm Hg; and/or diastolic, 90-99 mm Hg) irrespective of cardiovascular risk, although they add that for patients in the lower blood pressure range who have no hypertension-mediated organ damage and who are at low cardiovascular risk, consideration may be given to starting treatment with lifestyle changes only. If, however, blood pressure control is not achieved within a few months of a lifestyle-based approach alone, drug treatment is necessary.
For older patients (aged 80 or older), the task force recommends initiation of drug treatment at 160 mm Hg systolic, although a lower systolic threshold of 140-160 mm Hg may be considered. The authors note that thresholds for the initiation of drug treatment for very frail patients should be individualized.
Blood pressure targets
In the new guidelines, the blood pressure target is the same as in the previous guidelines for the general population of patients with hypertension. The goal is < 140/80 mm Hg for most patients. This accounts for the major portion of the protective effect of blood pressure lowering.
However, the consensus document notes that despite the smaller incremental benefit, an effort should be made to reach a range of 120-129/70-79 mm Hg, but only if treatment is well tolerated to avoid the risk of treatment discontinuation because of adverse events, which might offset, in part or completely, the incremental reduction in cardiovascular outcomes.
Elaborating on this, Dr. Kreutz said, “We should aim for the systolic blood pressure to be within the range of below 140 mm Hg down to 120 mm Hg, with a specific target of around 130 mm Hg for most patients and lower in patients in whom drug treatments are well tolerated and who are at high risk.
“The problem is, if we go for a target of lower that 130 mm Hg, the evidence gets weaker, the benefits diminish, and we risk losing patients because of adverse effects from using so many drugs,” he added. “But in younger and fitter patients, we would recommend the lower the better, but not below 120 mm Hg.”
Dr. Kreutz noted that the new guidelines have tried to simplify recommendations on target pressures. “We have tried to simplify guidance to focus on a target of around 130 for almost all patients. Before, it wasn’t so clear. There were different targets for different groups of patients with various comorbidities or older patients. But now we are saying the range of 120 to 139 is suitable for the vast majority of patients.”
The guidelines do allow slightly higher targets for older and very frail patients.
Drug treatments
The guidelines advise that blood pressure lowering be prioritized over the selection of specific antihypertensive drug classes. The use of any of the five major drug classes – angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium blockers, and thiazide/thiazidelike diuretics – and their combinations are recommended as the basis of antihypertensive treatment strategies.
They advise starting with a two-drug combination for most patients. The preferred combinations including a renin-angiotensin blocker (either an ACE inhibitor or an ARB) with a calcium blocker or a thiazide/thiazidelike diuretic, preferably in a single-pill combination to reduce pill burden and improve adherence and outcome.
If blood pressure is not controlled with the initial two-drug combination at the maximum recommended and tolerated dose of the respective components, treatment should be increased to a three-drug combination.
“We can control 60% of patients in the general hypertensive population with dual therapy, and up to 90% with triple therapy,” Dr. Kreutz said. “Only a small percentage need a fourth drug.”
A new feature of the guidelines is the upgrading of beta-blockers in the treatment algorithms.
“Beta-blockers may not have previously been considered as a first choice of antihypertensive medication, but we see that in clinical practice, many patients are actually treated with these drugs because there are so many conditions in which beta-blockers have a compelling evidence-based indication or are believed to be favorable,” he said. “So, we are now positioning beta-blockers as drugs that can be used at any step of the treatment algorithm if there is a guideline directed indication or other conditions for which they are thought to be beneficial.”
The guidelines also recommend that all drugs be given as once-daily preparations and that they be taken preferably in the morning.
“The new TIME study has established that there is no difference in outcome with morning or evening dosing, but we know that adherence is often better when drugs are taken in the morning, and it is not advisable to take diuretics in the evening,” Dr. Kreutz said.
‘True resistant hypertension’
The guidelines have introduced a new term, “true resistant hypertension,” defined as systolic blood pressure of ≥ 140 mm Hg or diastolic blood pressure of ≥ 90 mm Hg in the presence of the following conditions: the maximum recommended and tolerated doses of a three-drug combination comprising a renin-angiotensin system blocker (either an ACE inhibitor or an ARB), a calcium blocker, and a thiazide/thiazidelike diuretic were used; inadequate blood pressure control has been confirmed by ambulatory (preferable) or home blood pressure measurement; and various causes of pseudo-resistant hypertension (especially poor medication adherence) and secondary hypertension have been excluded.
“There are many patients who may appear to have resistant hypertension, but we need to screen them carefully to ensure they are adherent to treatment, and then most of these patients are found not to be truly resistant,” Dr. Kreutz explained. “We estimate that only about 5% of patients have true resistant hypertension.”
For these patients with true resistant hypertension, two treatment approaches are recommended.
For those who do not have advanced kidney disease (glomerular filtration rate > 40 mL/min), renal denervation can be considered. This is a new II B recommendation.
Dr. Kreutz noted that studies of renal denervation excluded patients with advanced kidney disease, so there are no data for this group. For these patients, the guidelines suggest that a combination diuretic approach (chlorthalidone with a loop diuretic) could be considered in light of the results of the recent CLICK study.
Differences from U.S. guidelines?
Commenting on the new European guidelines for this news organization, Paul Whelton, MD, chair of the most recent American College of Cardiology/American Heart Association hypertension guidelines committee, said: “Publication of these guidelines is important. I congratulate the European task force. It is an enormous amount of time and effort.”
Dr. Whelton, who is Show Chwan Chair in Global Public Health at Tulane University, New Orleans, and president of the World Hypertension League, added: “I would say the changes are incremental rather than major, but that is probably appropriate.”
He welcomed the greater emphasis on out-of-office blood pressure measurement, saying, “That’s where we should be headed.”
Asked how the European guidelines differ from the U.S. guidelines, Dr. Whelton commented: “There are differences, but they are not huge. The major hypertension guidelines across the world are much more alike than they are different.”
He pointed out that both the U.S. and European guidelines aim for a target blood pressure of 130/80 mm Hg for most patients but have different ways of issuing that advice.
“The Europeans recommend a minimum goal of 140/90 mm Hg, and if there are no issues, then press on to get to under 130/80 mm Hg. That’s kind of a two-step process,” he said. “In the U.S., we’ve gone for a more direct approach of just recommending less than 130/80 mm Hg.
“My fear with the European approach is that by saying, get to 140/90 mm Hg first, then move on to 130/80 mm Hg, is that you’re likely to lose people. And doctors could feel that 140/90 is fine.”
More effort needed on implementation
Dr. Whelton says that where all hypertension guidelines are lacking is in the implementation of the recommendations.
“We are all falling down on implementation,” he said. “We have a huge burden of illness, and it is a very cost-effective area for management, but still, rates of blood pressure control are very bad. Generally speaking, even with a very conservative target of 140/90, the best countries only have control rates of around 30%, and this can be as low as 8% in some low/middle-income countries.”
Dr. Whelton believes the approach to blood pressure management needs to change.
“We know that the current traditional model of care, where blood pressure is managed by your local doctor, is not working. It is hopeless,” he said. “That is not an indictment of these doctors. It’s just that they have more pressing issues to deal with, so we need to look at other models.”
He suggests that the way forward is through convenient, community-based care delivered by a team in which nonphysicians assist in much of the management and in which reliable, affordable medications are given at the point of care, with patients tracked with electronic health records so as to identify those who are not adhering to their medication regimens.
“We know that using simple protocols will work for the vast majority of people. We don’t need to individualize or complicate this too much. That tends to lose people in the process.”
Dr. Whelton makes the point that it is well known how to diagnose and treat hypertension, yet this is not being done well.
“We are doing these things really badly. In routine care, blood pressure is measured horribly. Nobody would accept a pilot of a plane saying he should be doing all these procedures but he’s too busy and it’s probably okay, but that’s the way blood pressure is often measured in clinical practice,” he added. “And we can’t really do a good job if were not measuring the key variable properly that the diagnosis is based on.”
Dr. Whelton also points out that the medical profession is not making enough effort to have patients reach target levels.
“If you’re in a country where very few people are being treated and very high pressures are common, then of course you have to focus on that group first. But in most of the Western world, we are long past that, so we can move on down the chain. We then get to a lot more people with moderately high blood pressure getting exposed to increases in risk, and while this is not quite as dramatic as those with very high pressures at the individual risk level, because there are so many of them, that’s where a lot of events are occurring,” he says.
“If we get everyone to 140/90 mm Hg, we can probably prevent 60% of blood pressure–related events. But if we can get them all down to 130 mm Hg systolic, then we can prevent 75%-80% of events. It’s often quite easy to get to that target, but patients need help and encouragement.”
Going forward, he concluded, guidelines should pivot to focus more on implementation.
“We all try to make the guidelines as approachable as possible, but they are encyclopedic, and many doctors just continue doing what they are doing. That is our big challenge.”
A version of this article first appeared on Medscape.com.
Diabetes may short circuit pembrolizumab benefits in NSCLC
TOPLINE:
METHODOLOGY:
- Investigators reviewed the medical records of 203 consecutive patients with metastatic NSCLC who received first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center in Israel.
- Overall, 1 in 4 patients (n = 51) had diabetes mellitus; most (n = 42) were being treated with oral hypoglycemic agents, frequently metformin, and 7 were taking insulin.
- Rates of tumors with PD‐L1 expression above 50% were not significantly different among patients with diabetes and those without.
TAKEAWAY:
- Overall, among patients with diabetes, median progression-free survival (PFS) was significantly shorter than among patients without diabetes (5.9 vs. 7.1 months), as was overall survival (12 vs. 21 months).
- Shorter overall survival was more pronounced among those with diabetes who received pembrolizumab alone (12 vs. 27 months) in comparison with patients who received pembrolizumab plus chemotherapy (14.3 vs. 19.4 months).
- After adjusting for potential confounders, multivariate analysis confirmed that diabetes was an independent risk factor for shorter PFS (hazard ratio, 1.67) and shorter overall survival (HR, 1.73) for patients with NSCLC.
- In a validation cohort of 452 patients with metastatic NSCLC, only 19.6% of those with diabetes continued to take pembrolizumab at 12 months versus 31.7% of those without diabetes.
IN PRACTICE:
“As NSCLC patients with [diabetes] constitute a significant subgroup, there is an urgent need to validate our findings and explore whether outcomes in these patients can be improved by better glycemic control,” the authors said, adding that “chemotherapy may offset some of the deleterious effects” of diabetes.
SOURCE:
The study was led by Yasmin Leshem, MD, PhD, of the Tel Aviv Sourasky Medical Center, and was published in Cancer.
LIMITATIONS:
- Without access to blood test results outside the hospital, the researchers could not determine whether better glycemic control might have improved outcomes.
- The incidence of type 1 or 2 diabetes was not well documented.
DISCLOSURES:
- No funding source was reported.
- Two investigators reported receiving consulting and/or other fees from Bristol-Myers Squibb, Roche, Merck, Novartis, and Merck Sharp and Dohme.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators reviewed the medical records of 203 consecutive patients with metastatic NSCLC who received first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center in Israel.
- Overall, 1 in 4 patients (n = 51) had diabetes mellitus; most (n = 42) were being treated with oral hypoglycemic agents, frequently metformin, and 7 were taking insulin.
- Rates of tumors with PD‐L1 expression above 50% were not significantly different among patients with diabetes and those without.
TAKEAWAY:
- Overall, among patients with diabetes, median progression-free survival (PFS) was significantly shorter than among patients without diabetes (5.9 vs. 7.1 months), as was overall survival (12 vs. 21 months).
- Shorter overall survival was more pronounced among those with diabetes who received pembrolizumab alone (12 vs. 27 months) in comparison with patients who received pembrolizumab plus chemotherapy (14.3 vs. 19.4 months).
- After adjusting for potential confounders, multivariate analysis confirmed that diabetes was an independent risk factor for shorter PFS (hazard ratio, 1.67) and shorter overall survival (HR, 1.73) for patients with NSCLC.
- In a validation cohort of 452 patients with metastatic NSCLC, only 19.6% of those with diabetes continued to take pembrolizumab at 12 months versus 31.7% of those without diabetes.
IN PRACTICE:
“As NSCLC patients with [diabetes] constitute a significant subgroup, there is an urgent need to validate our findings and explore whether outcomes in these patients can be improved by better glycemic control,” the authors said, adding that “chemotherapy may offset some of the deleterious effects” of diabetes.
SOURCE:
The study was led by Yasmin Leshem, MD, PhD, of the Tel Aviv Sourasky Medical Center, and was published in Cancer.
LIMITATIONS:
- Without access to blood test results outside the hospital, the researchers could not determine whether better glycemic control might have improved outcomes.
- The incidence of type 1 or 2 diabetes was not well documented.
DISCLOSURES:
- No funding source was reported.
- Two investigators reported receiving consulting and/or other fees from Bristol-Myers Squibb, Roche, Merck, Novartis, and Merck Sharp and Dohme.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Investigators reviewed the medical records of 203 consecutive patients with metastatic NSCLC who received first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center in Israel.
- Overall, 1 in 4 patients (n = 51) had diabetes mellitus; most (n = 42) were being treated with oral hypoglycemic agents, frequently metformin, and 7 were taking insulin.
- Rates of tumors with PD‐L1 expression above 50% were not significantly different among patients with diabetes and those without.
TAKEAWAY:
- Overall, among patients with diabetes, median progression-free survival (PFS) was significantly shorter than among patients without diabetes (5.9 vs. 7.1 months), as was overall survival (12 vs. 21 months).
- Shorter overall survival was more pronounced among those with diabetes who received pembrolizumab alone (12 vs. 27 months) in comparison with patients who received pembrolizumab plus chemotherapy (14.3 vs. 19.4 months).
- After adjusting for potential confounders, multivariate analysis confirmed that diabetes was an independent risk factor for shorter PFS (hazard ratio, 1.67) and shorter overall survival (HR, 1.73) for patients with NSCLC.
- In a validation cohort of 452 patients with metastatic NSCLC, only 19.6% of those with diabetes continued to take pembrolizumab at 12 months versus 31.7% of those without diabetes.
IN PRACTICE:
“As NSCLC patients with [diabetes] constitute a significant subgroup, there is an urgent need to validate our findings and explore whether outcomes in these patients can be improved by better glycemic control,” the authors said, adding that “chemotherapy may offset some of the deleterious effects” of diabetes.
SOURCE:
The study was led by Yasmin Leshem, MD, PhD, of the Tel Aviv Sourasky Medical Center, and was published in Cancer.
LIMITATIONS:
- Without access to blood test results outside the hospital, the researchers could not determine whether better glycemic control might have improved outcomes.
- The incidence of type 1 or 2 diabetes was not well documented.
DISCLOSURES:
- No funding source was reported.
- Two investigators reported receiving consulting and/or other fees from Bristol-Myers Squibb, Roche, Merck, Novartis, and Merck Sharp and Dohme.
A version of this article first appeared on Medscape.com.
Cannabis for cancer symptoms: Perceived or real benefit?
TOPLINE:
METHODOLOGY:
- Participants included 267 adults (mean age, 58 years; 70% women; 88% White) undergoing treatment for cancer, most commonly breast (47%) and ovarian (29%).
- Participants completed online surveys to characterize cannabis use, reasons for using it, perceived benefits and harms, and physical/psychological symptoms.
- Participants who had used cannabis for more than 1 day during the previous 30 days were compared with those who had not.
TAKEAWAY:
- Overall, 26% of respondents reported cannabis use in the past 30 days, most often edibles (65%) or smoked cannabis (51%).
- Cannabis users were more likely to be younger, male, Black, to have lower income, worse physical/psychological symptoms, and to be disabled or unable to work in comparison with nonusers.
- Cannabis was used to treat pain, cancer, sleep problems, anxiety, nausea, and poor appetite; perceived benefits were greatest with respect to sleep, nausea, pain, muscle spasms, and anxiety.
- Despite perceived benefits, cannabis users reported worse overall distress, anxiety, sleep disturbances, appetite, nausea, fatigue, and pain.
IN PRACTICE:
“The study findings indicate that patients with cancer perceived benefits to using cannabis for many symptoms” but also revealed that “those who used cannabis in the past 30 days had significantly worse symptom profiles overall than those who did not use cannabis,” the authors wrote.
SOURCE:
The study, led by Desiree R. Azizoddin, PsyD, University of Oklahoma Health Science Center, Oklahoma City, was published online in Cancer.
LIMITATIONS:
It’s not known whether adults who used cannabis had significantly worse symptoms at the outset, which may have prompted cannabis use, or whether cannabis use may have exacerbated their symptoms.
DISCLOSURES:
Funding for the study was provided by grants from the National Cancer Institute and the Oklahoma Tobacco Settlement Endowment Trust. Nine of the 10 authors have disclosed no relevant conflicts of interest. One author has relationships with various pharmaceutical companies involved in oncology.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Participants included 267 adults (mean age, 58 years; 70% women; 88% White) undergoing treatment for cancer, most commonly breast (47%) and ovarian (29%).
- Participants completed online surveys to characterize cannabis use, reasons for using it, perceived benefits and harms, and physical/psychological symptoms.
- Participants who had used cannabis for more than 1 day during the previous 30 days were compared with those who had not.
TAKEAWAY:
- Overall, 26% of respondents reported cannabis use in the past 30 days, most often edibles (65%) or smoked cannabis (51%).
- Cannabis users were more likely to be younger, male, Black, to have lower income, worse physical/psychological symptoms, and to be disabled or unable to work in comparison with nonusers.
- Cannabis was used to treat pain, cancer, sleep problems, anxiety, nausea, and poor appetite; perceived benefits were greatest with respect to sleep, nausea, pain, muscle spasms, and anxiety.
- Despite perceived benefits, cannabis users reported worse overall distress, anxiety, sleep disturbances, appetite, nausea, fatigue, and pain.
IN PRACTICE:
“The study findings indicate that patients with cancer perceived benefits to using cannabis for many symptoms” but also revealed that “those who used cannabis in the past 30 days had significantly worse symptom profiles overall than those who did not use cannabis,” the authors wrote.
SOURCE:
The study, led by Desiree R. Azizoddin, PsyD, University of Oklahoma Health Science Center, Oklahoma City, was published online in Cancer.
LIMITATIONS:
It’s not known whether adults who used cannabis had significantly worse symptoms at the outset, which may have prompted cannabis use, or whether cannabis use may have exacerbated their symptoms.
DISCLOSURES:
Funding for the study was provided by grants from the National Cancer Institute and the Oklahoma Tobacco Settlement Endowment Trust. Nine of the 10 authors have disclosed no relevant conflicts of interest. One author has relationships with various pharmaceutical companies involved in oncology.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Participants included 267 adults (mean age, 58 years; 70% women; 88% White) undergoing treatment for cancer, most commonly breast (47%) and ovarian (29%).
- Participants completed online surveys to characterize cannabis use, reasons for using it, perceived benefits and harms, and physical/psychological symptoms.
- Participants who had used cannabis for more than 1 day during the previous 30 days were compared with those who had not.
TAKEAWAY:
- Overall, 26% of respondents reported cannabis use in the past 30 days, most often edibles (65%) or smoked cannabis (51%).
- Cannabis users were more likely to be younger, male, Black, to have lower income, worse physical/psychological symptoms, and to be disabled or unable to work in comparison with nonusers.
- Cannabis was used to treat pain, cancer, sleep problems, anxiety, nausea, and poor appetite; perceived benefits were greatest with respect to sleep, nausea, pain, muscle spasms, and anxiety.
- Despite perceived benefits, cannabis users reported worse overall distress, anxiety, sleep disturbances, appetite, nausea, fatigue, and pain.
IN PRACTICE:
“The study findings indicate that patients with cancer perceived benefits to using cannabis for many symptoms” but also revealed that “those who used cannabis in the past 30 days had significantly worse symptom profiles overall than those who did not use cannabis,” the authors wrote.
SOURCE:
The study, led by Desiree R. Azizoddin, PsyD, University of Oklahoma Health Science Center, Oklahoma City, was published online in Cancer.
LIMITATIONS:
It’s not known whether adults who used cannabis had significantly worse symptoms at the outset, which may have prompted cannabis use, or whether cannabis use may have exacerbated their symptoms.
DISCLOSURES:
Funding for the study was provided by grants from the National Cancer Institute and the Oklahoma Tobacco Settlement Endowment Trust. Nine of the 10 authors have disclosed no relevant conflicts of interest. One author has relationships with various pharmaceutical companies involved in oncology.
A version of this article first appeared on Medscape.com.