User login
Switching gears at high speed
Michigan hospitalists prepare for COVID-19 care
When March began, Valerie Vaughn, MD, split her time between caring for general inpatients at the University of Michigan’s hospitals in Ann Arbor and doing research on how to reduce overuse of antibiotics in hospitals nationwide.
By the time the month was over, she had helped create a new kind of hospital team focused on caring for patients with COVID-19, learned how to provide an intensive level of care for the sickest among them, trained hundreds of physicians in how to do the same, and created free online learning tools for physicians nationwide.
Call it switching gears while driving a race car. Changing horses in the middle of a raging river. Or going to medical boot camp. Whatever the metaphor, Dr. Vaughn and her colleagues did it.
And now they’re hoping that sharing what they learned will help others if their hospitals go through the same thing.
Near the epicenter
Michigan Medicine, the University of Michigan’s academic medical center, is a few dozen miles west of the Detroit hospitals that have become a national epicenter for COVID-19 cases. It’s gotten plenty of direct and transferred COVID-19 patients since mid-March.
When Dr. Vaughn’s boss, division of hospital medicine chief Vineet Chopra, MD, was tapped to lead the creation of an all-COVID unit, he asked Dr. Vaughn to work with him and the team of hospitalists, nurse practitioners, physician assistants, nurses, respiratory therapists, and other staff that had volunteered for the team.
They had 3 days to prepare.
The “SWAT team”, as Dr. Vaughn calls it, opened the RICU, or Regional Infectious Containment Unit, on March 16. They doubled the number of beds 2 weeks later.
By the end of March, the team had handed over the reins to a team of experienced intensive care professionals so the unit could focus on the sickest patients. And the RICU team had moved on to transforming other areas of the hospital, and training their staff, in the same way.
By early April, more than 200 beds across the University of Michigan’s hospitals were devoted to COVID-19 care. General medicine physicians who hadn’t practiced inside a hospital since their residency days – thanks to the ability to hand off to hospitalists – were being pulled into inpatient duty. Hospitalists were being pulled into caring for patients who would normally have been in the care of an intensive care team.
“What’s amazed me most is how much people have stepped up to the challenge,” says Dr. Vaughn. “As hard and uncomfortable as it is to do something you’re not typically doing, it can also be therapeutic to say how can I help, let me do something. Yes, they’re anxious, but they want to know how they can be as prepared as they can be, to be as helpful as possible to these patients.”
Dr. Chopra agrees. “The silver lining in all of this is that I have personally seen the best in us come to the surface. Nurses, physicians, pharmacists, and therapists have come together and have shown selflessness, kindness, empathy and resilience in profound ways.”
Making the leap
Even though they didn’t choose hospital medicine, or ICU medicine, as their specialty, physicians may greatly underestimate how useful they can be with a little just-in-time training and the help of residents, fellows, advanced practice providers, and experienced nurses and respiratory therapists.
That training is now available for free through Michigan Medicine’s new online COVID-19 CME portal. The session in “Inpatient Management of COVID-19 patients” provides an important overview for those who have never cared for a case, especially if they haven’t been on inpatient duty in a while. The ICU Bootcamp is for those who will be caring for sicker COVID-19 patients but haven’t practiced in an ICU for a while.
One of the most important roles of a COVID-19 inpatient physician, Dr. Vaughn notes, doesn’t involve new skills. Rather, it draws on the doctoring skills that general medicine and hospital medicine physicians have already honed: the ability to assess and treat the entire patient, to talk with families who can’t be with their loved ones, to humanize the experience for patients and their loved ones as much as possible, and to bring messages of love from the family back to the bedside.
By pairing a general medicine physician newly placed on inpatient duty with a resident, nurse practitioner, or physician assistant who can handle inpatient charting duties, the team can make the most of each kind of provider’s time. Administrators, too, can reduce the burden on the entire team by simplifying processes for what must be charted and recorded in the EMR.
“Hospitals facing a COVID-19 crunch need to make it easier for teams to focus on the medicine and the human connection” and to shorten the learning curve for those shifting into unfamiliar duties, she advises.
Other lessons learned
Placing COVID-19 patients on the same unit, and keeping non–COVID-19 patients in another area of the hospital, isn’t just a good idea for protecting uninfected patients, Dr. Vaughn notes. It’s also good for providers who are getting used to treating COVID-19 because they don’t have to shift between the needs of different types of patients as they go from room to room.
“The learning curve is steep, but after a couple of days taking care of these patients, you have a good feeling about how to care for them and a great sense of camaraderie with the rest of the team involved in caring for them,” she says. “Everyone jumps in to help because they know we’re in this as a team and that it’s OK for respiratory therapists to step up to help a physician who doesn’t know as much about ventilator care or for nurses to suggest medications based on what other physicians have used.”
The flattening of professional hierarchies long ingrained in hospitals may be a side effect of the tremendous and urgent sense of mission that has developed around responding to COVID-19, Dr. Vaughn notes.
Those stepping into new roles should invite their colleagues to alert them when they see them about to slip up on protective practices that might be new to them. Similarly, they should help each other resist the urge to rush into a COVID-19 patient’s room unprotected in order to help with an urgent situation. The safety of providers – to preserve their ability to care for the many more patients who will need them – must be paramount.
“To handle this pandemic, we need to all be all-in and working toward a common goal, without competing priorities,” she says. “We need to use everyone’s skill sets to the fullest, without creating burnout. We’re going to be different when all this is done.”
Avoiding provider burnout is harder than ever because team members caring for COVID-19 must stay apart from family at home and avoid in-person visits with loved ones and friends. Those who are switching to inpatient or ICU-level care should make a point of focusing on exercise, sleep, virtual connections with loved ones, and healthy eating in between shifts.
“You’re no good to anyone else if you’re not healthy,” Dr. Vaughn says. “Your mental and physical health have to come first because they enable you to help others.”
Paying attention to the appreciation that the community is showing health care workers can also brighten the day of a stressed COVID-19 inpatient clinician, she notes.
“All the little signs of love from the community – the thank you signs, sidewalk chalk drawings, hearts in people’s windows – really do help.”
This article is published courtesy of the University of Michigan Health Lab, where it appeared originally.
Michigan hospitalists prepare for COVID-19 care
Michigan hospitalists prepare for COVID-19 care
When March began, Valerie Vaughn, MD, split her time between caring for general inpatients at the University of Michigan’s hospitals in Ann Arbor and doing research on how to reduce overuse of antibiotics in hospitals nationwide.
By the time the month was over, she had helped create a new kind of hospital team focused on caring for patients with COVID-19, learned how to provide an intensive level of care for the sickest among them, trained hundreds of physicians in how to do the same, and created free online learning tools for physicians nationwide.
Call it switching gears while driving a race car. Changing horses in the middle of a raging river. Or going to medical boot camp. Whatever the metaphor, Dr. Vaughn and her colleagues did it.
And now they’re hoping that sharing what they learned will help others if their hospitals go through the same thing.
Near the epicenter
Michigan Medicine, the University of Michigan’s academic medical center, is a few dozen miles west of the Detroit hospitals that have become a national epicenter for COVID-19 cases. It’s gotten plenty of direct and transferred COVID-19 patients since mid-March.
When Dr. Vaughn’s boss, division of hospital medicine chief Vineet Chopra, MD, was tapped to lead the creation of an all-COVID unit, he asked Dr. Vaughn to work with him and the team of hospitalists, nurse practitioners, physician assistants, nurses, respiratory therapists, and other staff that had volunteered for the team.
They had 3 days to prepare.
The “SWAT team”, as Dr. Vaughn calls it, opened the RICU, or Regional Infectious Containment Unit, on March 16. They doubled the number of beds 2 weeks later.
By the end of March, the team had handed over the reins to a team of experienced intensive care professionals so the unit could focus on the sickest patients. And the RICU team had moved on to transforming other areas of the hospital, and training their staff, in the same way.
By early April, more than 200 beds across the University of Michigan’s hospitals were devoted to COVID-19 care. General medicine physicians who hadn’t practiced inside a hospital since their residency days – thanks to the ability to hand off to hospitalists – were being pulled into inpatient duty. Hospitalists were being pulled into caring for patients who would normally have been in the care of an intensive care team.
“What’s amazed me most is how much people have stepped up to the challenge,” says Dr. Vaughn. “As hard and uncomfortable as it is to do something you’re not typically doing, it can also be therapeutic to say how can I help, let me do something. Yes, they’re anxious, but they want to know how they can be as prepared as they can be, to be as helpful as possible to these patients.”
Dr. Chopra agrees. “The silver lining in all of this is that I have personally seen the best in us come to the surface. Nurses, physicians, pharmacists, and therapists have come together and have shown selflessness, kindness, empathy and resilience in profound ways.”
Making the leap
Even though they didn’t choose hospital medicine, or ICU medicine, as their specialty, physicians may greatly underestimate how useful they can be with a little just-in-time training and the help of residents, fellows, advanced practice providers, and experienced nurses and respiratory therapists.
That training is now available for free through Michigan Medicine’s new online COVID-19 CME portal. The session in “Inpatient Management of COVID-19 patients” provides an important overview for those who have never cared for a case, especially if they haven’t been on inpatient duty in a while. The ICU Bootcamp is for those who will be caring for sicker COVID-19 patients but haven’t practiced in an ICU for a while.
One of the most important roles of a COVID-19 inpatient physician, Dr. Vaughn notes, doesn’t involve new skills. Rather, it draws on the doctoring skills that general medicine and hospital medicine physicians have already honed: the ability to assess and treat the entire patient, to talk with families who can’t be with their loved ones, to humanize the experience for patients and their loved ones as much as possible, and to bring messages of love from the family back to the bedside.
By pairing a general medicine physician newly placed on inpatient duty with a resident, nurse practitioner, or physician assistant who can handle inpatient charting duties, the team can make the most of each kind of provider’s time. Administrators, too, can reduce the burden on the entire team by simplifying processes for what must be charted and recorded in the EMR.
“Hospitals facing a COVID-19 crunch need to make it easier for teams to focus on the medicine and the human connection” and to shorten the learning curve for those shifting into unfamiliar duties, she advises.
Other lessons learned
Placing COVID-19 patients on the same unit, and keeping non–COVID-19 patients in another area of the hospital, isn’t just a good idea for protecting uninfected patients, Dr. Vaughn notes. It’s also good for providers who are getting used to treating COVID-19 because they don’t have to shift between the needs of different types of patients as they go from room to room.
“The learning curve is steep, but after a couple of days taking care of these patients, you have a good feeling about how to care for them and a great sense of camaraderie with the rest of the team involved in caring for them,” she says. “Everyone jumps in to help because they know we’re in this as a team and that it’s OK for respiratory therapists to step up to help a physician who doesn’t know as much about ventilator care or for nurses to suggest medications based on what other physicians have used.”
The flattening of professional hierarchies long ingrained in hospitals may be a side effect of the tremendous and urgent sense of mission that has developed around responding to COVID-19, Dr. Vaughn notes.
Those stepping into new roles should invite their colleagues to alert them when they see them about to slip up on protective practices that might be new to them. Similarly, they should help each other resist the urge to rush into a COVID-19 patient’s room unprotected in order to help with an urgent situation. The safety of providers – to preserve their ability to care for the many more patients who will need them – must be paramount.
“To handle this pandemic, we need to all be all-in and working toward a common goal, without competing priorities,” she says. “We need to use everyone’s skill sets to the fullest, without creating burnout. We’re going to be different when all this is done.”
Avoiding provider burnout is harder than ever because team members caring for COVID-19 must stay apart from family at home and avoid in-person visits with loved ones and friends. Those who are switching to inpatient or ICU-level care should make a point of focusing on exercise, sleep, virtual connections with loved ones, and healthy eating in between shifts.
“You’re no good to anyone else if you’re not healthy,” Dr. Vaughn says. “Your mental and physical health have to come first because they enable you to help others.”
Paying attention to the appreciation that the community is showing health care workers can also brighten the day of a stressed COVID-19 inpatient clinician, she notes.
“All the little signs of love from the community – the thank you signs, sidewalk chalk drawings, hearts in people’s windows – really do help.”
This article is published courtesy of the University of Michigan Health Lab, where it appeared originally.
When March began, Valerie Vaughn, MD, split her time between caring for general inpatients at the University of Michigan’s hospitals in Ann Arbor and doing research on how to reduce overuse of antibiotics in hospitals nationwide.
By the time the month was over, she had helped create a new kind of hospital team focused on caring for patients with COVID-19, learned how to provide an intensive level of care for the sickest among them, trained hundreds of physicians in how to do the same, and created free online learning tools for physicians nationwide.
Call it switching gears while driving a race car. Changing horses in the middle of a raging river. Or going to medical boot camp. Whatever the metaphor, Dr. Vaughn and her colleagues did it.
And now they’re hoping that sharing what they learned will help others if their hospitals go through the same thing.
Near the epicenter
Michigan Medicine, the University of Michigan’s academic medical center, is a few dozen miles west of the Detroit hospitals that have become a national epicenter for COVID-19 cases. It’s gotten plenty of direct and transferred COVID-19 patients since mid-March.
When Dr. Vaughn’s boss, division of hospital medicine chief Vineet Chopra, MD, was tapped to lead the creation of an all-COVID unit, he asked Dr. Vaughn to work with him and the team of hospitalists, nurse practitioners, physician assistants, nurses, respiratory therapists, and other staff that had volunteered for the team.
They had 3 days to prepare.
The “SWAT team”, as Dr. Vaughn calls it, opened the RICU, or Regional Infectious Containment Unit, on March 16. They doubled the number of beds 2 weeks later.
By the end of March, the team had handed over the reins to a team of experienced intensive care professionals so the unit could focus on the sickest patients. And the RICU team had moved on to transforming other areas of the hospital, and training their staff, in the same way.
By early April, more than 200 beds across the University of Michigan’s hospitals were devoted to COVID-19 care. General medicine physicians who hadn’t practiced inside a hospital since their residency days – thanks to the ability to hand off to hospitalists – were being pulled into inpatient duty. Hospitalists were being pulled into caring for patients who would normally have been in the care of an intensive care team.
“What’s amazed me most is how much people have stepped up to the challenge,” says Dr. Vaughn. “As hard and uncomfortable as it is to do something you’re not typically doing, it can also be therapeutic to say how can I help, let me do something. Yes, they’re anxious, but they want to know how they can be as prepared as they can be, to be as helpful as possible to these patients.”
Dr. Chopra agrees. “The silver lining in all of this is that I have personally seen the best in us come to the surface. Nurses, physicians, pharmacists, and therapists have come together and have shown selflessness, kindness, empathy and resilience in profound ways.”
Making the leap
Even though they didn’t choose hospital medicine, or ICU medicine, as their specialty, physicians may greatly underestimate how useful they can be with a little just-in-time training and the help of residents, fellows, advanced practice providers, and experienced nurses and respiratory therapists.
That training is now available for free through Michigan Medicine’s new online COVID-19 CME portal. The session in “Inpatient Management of COVID-19 patients” provides an important overview for those who have never cared for a case, especially if they haven’t been on inpatient duty in a while. The ICU Bootcamp is for those who will be caring for sicker COVID-19 patients but haven’t practiced in an ICU for a while.
One of the most important roles of a COVID-19 inpatient physician, Dr. Vaughn notes, doesn’t involve new skills. Rather, it draws on the doctoring skills that general medicine and hospital medicine physicians have already honed: the ability to assess and treat the entire patient, to talk with families who can’t be with their loved ones, to humanize the experience for patients and their loved ones as much as possible, and to bring messages of love from the family back to the bedside.
By pairing a general medicine physician newly placed on inpatient duty with a resident, nurse practitioner, or physician assistant who can handle inpatient charting duties, the team can make the most of each kind of provider’s time. Administrators, too, can reduce the burden on the entire team by simplifying processes for what must be charted and recorded in the EMR.
“Hospitals facing a COVID-19 crunch need to make it easier for teams to focus on the medicine and the human connection” and to shorten the learning curve for those shifting into unfamiliar duties, she advises.
Other lessons learned
Placing COVID-19 patients on the same unit, and keeping non–COVID-19 patients in another area of the hospital, isn’t just a good idea for protecting uninfected patients, Dr. Vaughn notes. It’s also good for providers who are getting used to treating COVID-19 because they don’t have to shift between the needs of different types of patients as they go from room to room.
“The learning curve is steep, but after a couple of days taking care of these patients, you have a good feeling about how to care for them and a great sense of camaraderie with the rest of the team involved in caring for them,” she says. “Everyone jumps in to help because they know we’re in this as a team and that it’s OK for respiratory therapists to step up to help a physician who doesn’t know as much about ventilator care or for nurses to suggest medications based on what other physicians have used.”
The flattening of professional hierarchies long ingrained in hospitals may be a side effect of the tremendous and urgent sense of mission that has developed around responding to COVID-19, Dr. Vaughn notes.
Those stepping into new roles should invite their colleagues to alert them when they see them about to slip up on protective practices that might be new to them. Similarly, they should help each other resist the urge to rush into a COVID-19 patient’s room unprotected in order to help with an urgent situation. The safety of providers – to preserve their ability to care for the many more patients who will need them – must be paramount.
“To handle this pandemic, we need to all be all-in and working toward a common goal, without competing priorities,” she says. “We need to use everyone’s skill sets to the fullest, without creating burnout. We’re going to be different when all this is done.”
Avoiding provider burnout is harder than ever because team members caring for COVID-19 must stay apart from family at home and avoid in-person visits with loved ones and friends. Those who are switching to inpatient or ICU-level care should make a point of focusing on exercise, sleep, virtual connections with loved ones, and healthy eating in between shifts.
“You’re no good to anyone else if you’re not healthy,” Dr. Vaughn says. “Your mental and physical health have to come first because they enable you to help others.”
Paying attention to the appreciation that the community is showing health care workers can also brighten the day of a stressed COVID-19 inpatient clinician, she notes.
“All the little signs of love from the community – the thank you signs, sidewalk chalk drawings, hearts in people’s windows – really do help.”
This article is published courtesy of the University of Michigan Health Lab, where it appeared originally.
2019-2020 flu season ends with ‘very high’ activity in New Jersey
The 2019-2020 flu season is ending, but not without a revised map to reflect the COVID-induced new world order.
For the week ending April 11, those additions encompass only New Jersey at level 13 and New York City at level 12, the CDC reported April 17.
Eight states, plus the District of Columbia and Puerto Rico, were in the “high” range of flu activity, which runs from level 8 to level 10, for the same week. Those eight states included Connecticut, Georgia, Louisiana, Maryland, Massachusetts, New York, South Carolina, and Wisconsin.
The CDC’s influenza division included this note with its latest FluView report: “The COVID-19 pandemic is affecting healthcare seeking behavior. The number of persons and their reasons for seeking care in the outpatient and ED settings is changing. These changes impact data from ILINet [Outpatient Influenza-like Illness Surveillance Network] in ways that are difficult to differentiate from changes in illness levels, therefore ILINet data should be interpreted with caution.”
Outpatient visits for influenza-like illness made up 2.9% of all visits to health care providers for the week ending April 11, which is the 23rd consecutive week that it’s been at or above the national baseline level of 2.4%. Twenty-three weeks is longer than this has occurred during any flu season since the CDC started setting a baseline in 2007, according to ILINet data.
Mortality from pneumonia and influenza, at 11.7%, was well above the epidemic threshold of 7.0%, although, again, pneumonia mortality “is being driven primarily by an increase in non-influenza pneumonia deaths due to COVID-19,” the CDC wrote.
The total number of influenza-related deaths in children, with reports of two more added this week, is 168 for the season – higher than two of the last three seasons: 144 in 2018-2019, 188 in 2017-2018, and 110 in 2016-2017, according to the CDC.
The 2019-2020 flu season is ending, but not without a revised map to reflect the COVID-induced new world order.
For the week ending April 11, those additions encompass only New Jersey at level 13 and New York City at level 12, the CDC reported April 17.
Eight states, plus the District of Columbia and Puerto Rico, were in the “high” range of flu activity, which runs from level 8 to level 10, for the same week. Those eight states included Connecticut, Georgia, Louisiana, Maryland, Massachusetts, New York, South Carolina, and Wisconsin.
The CDC’s influenza division included this note with its latest FluView report: “The COVID-19 pandemic is affecting healthcare seeking behavior. The number of persons and their reasons for seeking care in the outpatient and ED settings is changing. These changes impact data from ILINet [Outpatient Influenza-like Illness Surveillance Network] in ways that are difficult to differentiate from changes in illness levels, therefore ILINet data should be interpreted with caution.”
Outpatient visits for influenza-like illness made up 2.9% of all visits to health care providers for the week ending April 11, which is the 23rd consecutive week that it’s been at or above the national baseline level of 2.4%. Twenty-three weeks is longer than this has occurred during any flu season since the CDC started setting a baseline in 2007, according to ILINet data.
Mortality from pneumonia and influenza, at 11.7%, was well above the epidemic threshold of 7.0%, although, again, pneumonia mortality “is being driven primarily by an increase in non-influenza pneumonia deaths due to COVID-19,” the CDC wrote.
The total number of influenza-related deaths in children, with reports of two more added this week, is 168 for the season – higher than two of the last three seasons: 144 in 2018-2019, 188 in 2017-2018, and 110 in 2016-2017, according to the CDC.
The 2019-2020 flu season is ending, but not without a revised map to reflect the COVID-induced new world order.
For the week ending April 11, those additions encompass only New Jersey at level 13 and New York City at level 12, the CDC reported April 17.
Eight states, plus the District of Columbia and Puerto Rico, were in the “high” range of flu activity, which runs from level 8 to level 10, for the same week. Those eight states included Connecticut, Georgia, Louisiana, Maryland, Massachusetts, New York, South Carolina, and Wisconsin.
The CDC’s influenza division included this note with its latest FluView report: “The COVID-19 pandemic is affecting healthcare seeking behavior. The number of persons and their reasons for seeking care in the outpatient and ED settings is changing. These changes impact data from ILINet [Outpatient Influenza-like Illness Surveillance Network] in ways that are difficult to differentiate from changes in illness levels, therefore ILINet data should be interpreted with caution.”
Outpatient visits for influenza-like illness made up 2.9% of all visits to health care providers for the week ending April 11, which is the 23rd consecutive week that it’s been at or above the national baseline level of 2.4%. Twenty-three weeks is longer than this has occurred during any flu season since the CDC started setting a baseline in 2007, according to ILINet data.
Mortality from pneumonia and influenza, at 11.7%, was well above the epidemic threshold of 7.0%, although, again, pneumonia mortality “is being driven primarily by an increase in non-influenza pneumonia deaths due to COVID-19,” the CDC wrote.
The total number of influenza-related deaths in children, with reports of two more added this week, is 168 for the season – higher than two of the last three seasons: 144 in 2018-2019, 188 in 2017-2018, and 110 in 2016-2017, according to the CDC.
COVID-19 mythconceptions
Let’s start with a case:
A 37-year-old woman is seen in clinic for a 5-day history of cough, fever, chest tightness, and onset of dyspnea on the day of her office visit.
An exam reveals her blood pressure is 100/60 mm Hg, her pulse is 100 beats per minute, her temperature is 38.7° C, her oxygen saturation is 93%, and her respiratory rate is 20 breaths per minute.
Auscultation of the chest revealed bilateral wheezing and rhonchi. A nasopharyngeal swab is sent for COVID-19 and is negative; she also tests negative for influenza.
Her hemoglobin level is 13 g/dL, hematocrit was 39%, platelet count was 155,000 per mcL of blood, and D-dimer level was 8.4 mcg/mL (normal is less than 0.4 mcg/mL.) Her white blood cell count was 6,000 per mcL of blood (neutrophils, 4,900; lymphocytes, 800; basophils, 200). Her chest x-ray showed bilateral lower lobe infiltrates.
What do you recommend?
A. Begin azithromycin plus ceftriaxone
B. Begin azithromycin
C. Begin oseltamivir
D. Obtain chest CT
E. Repeat COVID-19 test
With the massive amount of information coming out every day on COVID-19, it is hard to keep up with all of it, and sort out accurate, reviewed studies. We are in a position where we need to take in what we can and assess the best data available.
In the case above, I think choices D or E would make sense. This patient very likely has COVID-19 based on clinical symptoms and lab parameters. The negative COVID-19 test gives us pause, but several studies show that false negative tests are not uncommon.
Long et al. reported on 36 patients who had received both chest CT and real-time reverse transcription polymerase chain reaction (rRT-PCR) for COVID-19.1 All were eventually diagnosed with COVID-19 pneumonia. The CT scan had a very high sensitivity (35/36) of 97.2%, whereas the rRT-PCR had a lower sensitivity (30/36) of 83%. All six of the patients with a negative COVID-19 test initially were positive on repeat testing (three on the second test, three on the third test).
There are concerns about what the sensitivity of the rRT-PCR tests being run in the United States are. At this point, I think that, when the pretest probability of COVID-19 infection is very high based on local epidemiology and clinical symptoms, a negative COVID rRT-PCR does not eliminate the diagnosis. In many cases, COVID-19 may still be the most likely diagnosis.
Early in the pandemic, the symptoms that were emphasized were fever, cough, and dyspnea. Those were all crucial symptoms for a disease that causes pneumonia. GI symptoms were initially deemphasized. In an early study released from Wuhan, China, only about 5% of COVID-19 patients had nausea or diarrhea.2 In a study of 305 patients focused on gastrointestinal symptoms, half of the patients had diarrhea, half had anorexia and 30% had nausea.3 In a small series of nine patients who presented with only GI symptoms, four of these patients never developed fever or pulmonary symptoms.3
On March 14, the French health minister, Olivier Véran, tweeted that “taking anti-inflammatory drugs (ibuprofen, cortisone ...) could be an aggravating factor for the infection. If you have a fever, take paracetamol.” This was picked up by many news services, and soon became standard recommendations, despite no data.
There is reason for concern for NSAIDs, as regular NSAID use has been tied to more complications in patients with respiratory tract infections.4 I have never been a proponent of regular NSAID use in patients who are infected, because the likelihood of toxicity is elevated in patients who are volume depleted or under physiologic stress. But at this time, there is no evidence on problems with episodic NSAID use in patients with COVID-19.
Another widely disseminated decree was that patients with COVID-19 should not use ACE inhibitors and angiotensin II receptor blockers (ARBs). COVID-19 binds to their target cells through ACE2, which is expressed by epithelial cells of the lung, intestine and kidney. Patients who are treated with ACE inhibitors and ARBs have been shown to have more ACE2 expression.
In a letter to the editor by Fang et al. published in Lancet Respiratory Medicine, the authors raised the question of whether patients might be better served to be switched from ACE inhibitors and ARBs to calcium-channel blockers for the treatment of hypertension.5 A small study by Meng et al. looked at outcomes of patients on these drugs who had COVID-19 infection.6 They looked at 417 patients admitted to a hospital in China with COVID-19 infection. A total of 42 patients were on medications for hypertension. Group 1 were patients on ACE inhibitors/ARBs (17 patients) and group 2 were patients on other antihypertensives (25 patients). During hospitalization 12 patients (48%) in group 2 were categorized as having severe disease and 1 patient died. In group 1 (the ACE inhibitor/ARB–treated patients) only four (23%) were categorized as having severe disease, and no patients in this group died.
Vaduganathan et al. published a special report in the New England Journal of Medicine strongly arguing the point that “[u]ntil further data are available, we think that [renin-angiotensin-aldosterone system] inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with COVID-19”.7 This position is supported by the American Heart Association, the American College of Cardiology, the American College of Physicians, and 11 other medical organizations.
Take-home messages
- Testing isn’t perfect – if you have strong suspicion for COVID-19 disease, retest.
- GI symptoms appear to be common, and rarely may be the only symptoms initially.
- NSAIDs are always risky in really sick patients, but data specific to COVID-19 is lacking.
- ACE inhibitors/ARBs should not be avoided in patients with COVID-19.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact Dr. Paauw at imnews@mdedge.com.
References
1. Long C et al. Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? Eur J Radiol. 2020 Mar 25;126:108961.
2. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
3. Tian Y et al. Review article: Gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020;00:1–9.
4. Voiriot G et al. Risks related to the use of nonsteroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients. J Clin Med. 2019;8:E786.
5. Fang L et al. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Mar 11. doi:10.1016/S2213-2600(20)30116-8.
6. Meng J et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020 Dec;9(1):757-60.
7. Vaduganathan M et al. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med. 2020 Mar 30. doi: 10.1056/NEJMsr2005760.
Let’s start with a case:
A 37-year-old woman is seen in clinic for a 5-day history of cough, fever, chest tightness, and onset of dyspnea on the day of her office visit.
An exam reveals her blood pressure is 100/60 mm Hg, her pulse is 100 beats per minute, her temperature is 38.7° C, her oxygen saturation is 93%, and her respiratory rate is 20 breaths per minute.
Auscultation of the chest revealed bilateral wheezing and rhonchi. A nasopharyngeal swab is sent for COVID-19 and is negative; she also tests negative for influenza.
Her hemoglobin level is 13 g/dL, hematocrit was 39%, platelet count was 155,000 per mcL of blood, and D-dimer level was 8.4 mcg/mL (normal is less than 0.4 mcg/mL.) Her white blood cell count was 6,000 per mcL of blood (neutrophils, 4,900; lymphocytes, 800; basophils, 200). Her chest x-ray showed bilateral lower lobe infiltrates.
What do you recommend?
A. Begin azithromycin plus ceftriaxone
B. Begin azithromycin
C. Begin oseltamivir
D. Obtain chest CT
E. Repeat COVID-19 test
With the massive amount of information coming out every day on COVID-19, it is hard to keep up with all of it, and sort out accurate, reviewed studies. We are in a position where we need to take in what we can and assess the best data available.
In the case above, I think choices D or E would make sense. This patient very likely has COVID-19 based on clinical symptoms and lab parameters. The negative COVID-19 test gives us pause, but several studies show that false negative tests are not uncommon.
Long et al. reported on 36 patients who had received both chest CT and real-time reverse transcription polymerase chain reaction (rRT-PCR) for COVID-19.1 All were eventually diagnosed with COVID-19 pneumonia. The CT scan had a very high sensitivity (35/36) of 97.2%, whereas the rRT-PCR had a lower sensitivity (30/36) of 83%. All six of the patients with a negative COVID-19 test initially were positive on repeat testing (three on the second test, three on the third test).
There are concerns about what the sensitivity of the rRT-PCR tests being run in the United States are. At this point, I think that, when the pretest probability of COVID-19 infection is very high based on local epidemiology and clinical symptoms, a negative COVID rRT-PCR does not eliminate the diagnosis. In many cases, COVID-19 may still be the most likely diagnosis.
Early in the pandemic, the symptoms that were emphasized were fever, cough, and dyspnea. Those were all crucial symptoms for a disease that causes pneumonia. GI symptoms were initially deemphasized. In an early study released from Wuhan, China, only about 5% of COVID-19 patients had nausea or diarrhea.2 In a study of 305 patients focused on gastrointestinal symptoms, half of the patients had diarrhea, half had anorexia and 30% had nausea.3 In a small series of nine patients who presented with only GI symptoms, four of these patients never developed fever or pulmonary symptoms.3
On March 14, the French health minister, Olivier Véran, tweeted that “taking anti-inflammatory drugs (ibuprofen, cortisone ...) could be an aggravating factor for the infection. If you have a fever, take paracetamol.” This was picked up by many news services, and soon became standard recommendations, despite no data.
There is reason for concern for NSAIDs, as regular NSAID use has been tied to more complications in patients with respiratory tract infections.4 I have never been a proponent of regular NSAID use in patients who are infected, because the likelihood of toxicity is elevated in patients who are volume depleted or under physiologic stress. But at this time, there is no evidence on problems with episodic NSAID use in patients with COVID-19.
Another widely disseminated decree was that patients with COVID-19 should not use ACE inhibitors and angiotensin II receptor blockers (ARBs). COVID-19 binds to their target cells through ACE2, which is expressed by epithelial cells of the lung, intestine and kidney. Patients who are treated with ACE inhibitors and ARBs have been shown to have more ACE2 expression.
In a letter to the editor by Fang et al. published in Lancet Respiratory Medicine, the authors raised the question of whether patients might be better served to be switched from ACE inhibitors and ARBs to calcium-channel blockers for the treatment of hypertension.5 A small study by Meng et al. looked at outcomes of patients on these drugs who had COVID-19 infection.6 They looked at 417 patients admitted to a hospital in China with COVID-19 infection. A total of 42 patients were on medications for hypertension. Group 1 were patients on ACE inhibitors/ARBs (17 patients) and group 2 were patients on other antihypertensives (25 patients). During hospitalization 12 patients (48%) in group 2 were categorized as having severe disease and 1 patient died. In group 1 (the ACE inhibitor/ARB–treated patients) only four (23%) were categorized as having severe disease, and no patients in this group died.
Vaduganathan et al. published a special report in the New England Journal of Medicine strongly arguing the point that “[u]ntil further data are available, we think that [renin-angiotensin-aldosterone system] inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with COVID-19”.7 This position is supported by the American Heart Association, the American College of Cardiology, the American College of Physicians, and 11 other medical organizations.
Take-home messages
- Testing isn’t perfect – if you have strong suspicion for COVID-19 disease, retest.
- GI symptoms appear to be common, and rarely may be the only symptoms initially.
- NSAIDs are always risky in really sick patients, but data specific to COVID-19 is lacking.
- ACE inhibitors/ARBs should not be avoided in patients with COVID-19.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact Dr. Paauw at imnews@mdedge.com.
References
1. Long C et al. Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? Eur J Radiol. 2020 Mar 25;126:108961.
2. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
3. Tian Y et al. Review article: Gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020;00:1–9.
4. Voiriot G et al. Risks related to the use of nonsteroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients. J Clin Med. 2019;8:E786.
5. Fang L et al. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Mar 11. doi:10.1016/S2213-2600(20)30116-8.
6. Meng J et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020 Dec;9(1):757-60.
7. Vaduganathan M et al. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med. 2020 Mar 30. doi: 10.1056/NEJMsr2005760.
Let’s start with a case:
A 37-year-old woman is seen in clinic for a 5-day history of cough, fever, chest tightness, and onset of dyspnea on the day of her office visit.
An exam reveals her blood pressure is 100/60 mm Hg, her pulse is 100 beats per minute, her temperature is 38.7° C, her oxygen saturation is 93%, and her respiratory rate is 20 breaths per minute.
Auscultation of the chest revealed bilateral wheezing and rhonchi. A nasopharyngeal swab is sent for COVID-19 and is negative; she also tests negative for influenza.
Her hemoglobin level is 13 g/dL, hematocrit was 39%, platelet count was 155,000 per mcL of blood, and D-dimer level was 8.4 mcg/mL (normal is less than 0.4 mcg/mL.) Her white blood cell count was 6,000 per mcL of blood (neutrophils, 4,900; lymphocytes, 800; basophils, 200). Her chest x-ray showed bilateral lower lobe infiltrates.
What do you recommend?
A. Begin azithromycin plus ceftriaxone
B. Begin azithromycin
C. Begin oseltamivir
D. Obtain chest CT
E. Repeat COVID-19 test
With the massive amount of information coming out every day on COVID-19, it is hard to keep up with all of it, and sort out accurate, reviewed studies. We are in a position where we need to take in what we can and assess the best data available.
In the case above, I think choices D or E would make sense. This patient very likely has COVID-19 based on clinical symptoms and lab parameters. The negative COVID-19 test gives us pause, but several studies show that false negative tests are not uncommon.
Long et al. reported on 36 patients who had received both chest CT and real-time reverse transcription polymerase chain reaction (rRT-PCR) for COVID-19.1 All were eventually diagnosed with COVID-19 pneumonia. The CT scan had a very high sensitivity (35/36) of 97.2%, whereas the rRT-PCR had a lower sensitivity (30/36) of 83%. All six of the patients with a negative COVID-19 test initially were positive on repeat testing (three on the second test, three on the third test).
There are concerns about what the sensitivity of the rRT-PCR tests being run in the United States are. At this point, I think that, when the pretest probability of COVID-19 infection is very high based on local epidemiology and clinical symptoms, a negative COVID rRT-PCR does not eliminate the diagnosis. In many cases, COVID-19 may still be the most likely diagnosis.
Early in the pandemic, the symptoms that were emphasized were fever, cough, and dyspnea. Those were all crucial symptoms for a disease that causes pneumonia. GI symptoms were initially deemphasized. In an early study released from Wuhan, China, only about 5% of COVID-19 patients had nausea or diarrhea.2 In a study of 305 patients focused on gastrointestinal symptoms, half of the patients had diarrhea, half had anorexia and 30% had nausea.3 In a small series of nine patients who presented with only GI symptoms, four of these patients never developed fever or pulmonary symptoms.3
On March 14, the French health minister, Olivier Véran, tweeted that “taking anti-inflammatory drugs (ibuprofen, cortisone ...) could be an aggravating factor for the infection. If you have a fever, take paracetamol.” This was picked up by many news services, and soon became standard recommendations, despite no data.
There is reason for concern for NSAIDs, as regular NSAID use has been tied to more complications in patients with respiratory tract infections.4 I have never been a proponent of regular NSAID use in patients who are infected, because the likelihood of toxicity is elevated in patients who are volume depleted or under physiologic stress. But at this time, there is no evidence on problems with episodic NSAID use in patients with COVID-19.
Another widely disseminated decree was that patients with COVID-19 should not use ACE inhibitors and angiotensin II receptor blockers (ARBs). COVID-19 binds to their target cells through ACE2, which is expressed by epithelial cells of the lung, intestine and kidney. Patients who are treated with ACE inhibitors and ARBs have been shown to have more ACE2 expression.
In a letter to the editor by Fang et al. published in Lancet Respiratory Medicine, the authors raised the question of whether patients might be better served to be switched from ACE inhibitors and ARBs to calcium-channel blockers for the treatment of hypertension.5 A small study by Meng et al. looked at outcomes of patients on these drugs who had COVID-19 infection.6 They looked at 417 patients admitted to a hospital in China with COVID-19 infection. A total of 42 patients were on medications for hypertension. Group 1 were patients on ACE inhibitors/ARBs (17 patients) and group 2 were patients on other antihypertensives (25 patients). During hospitalization 12 patients (48%) in group 2 were categorized as having severe disease and 1 patient died. In group 1 (the ACE inhibitor/ARB–treated patients) only four (23%) were categorized as having severe disease, and no patients in this group died.
Vaduganathan et al. published a special report in the New England Journal of Medicine strongly arguing the point that “[u]ntil further data are available, we think that [renin-angiotensin-aldosterone system] inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with COVID-19”.7 This position is supported by the American Heart Association, the American College of Cardiology, the American College of Physicians, and 11 other medical organizations.
Take-home messages
- Testing isn’t perfect – if you have strong suspicion for COVID-19 disease, retest.
- GI symptoms appear to be common, and rarely may be the only symptoms initially.
- NSAIDs are always risky in really sick patients, but data specific to COVID-19 is lacking.
- ACE inhibitors/ARBs should not be avoided in patients with COVID-19.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact Dr. Paauw at imnews@mdedge.com.
References
1. Long C et al. Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? Eur J Radiol. 2020 Mar 25;126:108961.
2. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
3. Tian Y et al. Review article: Gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020;00:1–9.
4. Voiriot G et al. Risks related to the use of nonsteroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients. J Clin Med. 2019;8:E786.
5. Fang L et al. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Mar 11. doi:10.1016/S2213-2600(20)30116-8.
6. Meng J et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020 Dec;9(1):757-60.
7. Vaduganathan M et al. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med. 2020 Mar 30. doi: 10.1056/NEJMsr2005760.
Should ART for HIV be initiated prior to tuberculosis testing results?
Tuberculosis symptoms as defined by the World Health Organization were effective in identifying patients with TB for the purposes of same-day antiretroviral therapy (ART) initiation in patients diagnosed with HIV, according to a pooled study of patients in two clinical trials. Guidelines suggest that patients with one or more TB symptoms be investigated for active TB before initiation of ART.
However, more than 80% of patients with TB symptoms did not have the disease and faced a delay of ART initiation, despite the many benefits of same-day ART initiation, according to the study presented online at the Conference on Retroviruses & Opportunistic Infections. This year CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
In her presentation, Alana T. Brennan, PhD, of the Boston University School of Public Health discussed the pooled results of 834 patients in the SLATE (Simple Algorithm for Treatment Eligibility) I and SLATE II trials. These two trials, conducted in South Africa and Kenya, respectively, assessed two variations of a simplified algorithm for eligibility for same-day ART initiation.
A total of 834 patients at baseline reported any self-described symptoms of TB using the WHO four-symptom TB screen (cough, fever, weight loss, night sweats). Those patients with any TB symptoms were assessed by sputum samples. The outcomes were prevalence of TB symptoms, TB diagnosis, and treatment.
Among the 834 patients, 493 (60%) reported no symptoms; 215 (26%) reported one to two symptoms, and 120 (14%) reported three to four symptoms. Only 66% of the patients with one to two symptoms were tested for TB; 78% of the patients with three to four symptoms were tested. Of these, only 1% of the patients with one to two symptoms tested positive for TB, and only 2% of the patients with three to four symptoms tested positive, according to Dr. Brennan.
“More than 80% of patients with TB symptoms did not have TB, but faced delay in ART initiation. No same-day [ART] initiators reported adverse events, so we hope that there would be some reconsideration of the requirement of TB testing prior to ART initiation due to any symptom of TB. … A potential consideration of the severity of the symptoms a patient has is necessary,” Dr. Brennan concluded.
Dr. Brennan reported that there were no disclosures.
SOURCE: Brennan AT et al. CROI 2020, Abstract 720.
Tuberculosis symptoms as defined by the World Health Organization were effective in identifying patients with TB for the purposes of same-day antiretroviral therapy (ART) initiation in patients diagnosed with HIV, according to a pooled study of patients in two clinical trials. Guidelines suggest that patients with one or more TB symptoms be investigated for active TB before initiation of ART.
However, more than 80% of patients with TB symptoms did not have the disease and faced a delay of ART initiation, despite the many benefits of same-day ART initiation, according to the study presented online at the Conference on Retroviruses & Opportunistic Infections. This year CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
In her presentation, Alana T. Brennan, PhD, of the Boston University School of Public Health discussed the pooled results of 834 patients in the SLATE (Simple Algorithm for Treatment Eligibility) I and SLATE II trials. These two trials, conducted in South Africa and Kenya, respectively, assessed two variations of a simplified algorithm for eligibility for same-day ART initiation.
A total of 834 patients at baseline reported any self-described symptoms of TB using the WHO four-symptom TB screen (cough, fever, weight loss, night sweats). Those patients with any TB symptoms were assessed by sputum samples. The outcomes were prevalence of TB symptoms, TB diagnosis, and treatment.
Among the 834 patients, 493 (60%) reported no symptoms; 215 (26%) reported one to two symptoms, and 120 (14%) reported three to four symptoms. Only 66% of the patients with one to two symptoms were tested for TB; 78% of the patients with three to four symptoms were tested. Of these, only 1% of the patients with one to two symptoms tested positive for TB, and only 2% of the patients with three to four symptoms tested positive, according to Dr. Brennan.
“More than 80% of patients with TB symptoms did not have TB, but faced delay in ART initiation. No same-day [ART] initiators reported adverse events, so we hope that there would be some reconsideration of the requirement of TB testing prior to ART initiation due to any symptom of TB. … A potential consideration of the severity of the symptoms a patient has is necessary,” Dr. Brennan concluded.
Dr. Brennan reported that there were no disclosures.
SOURCE: Brennan AT et al. CROI 2020, Abstract 720.
Tuberculosis symptoms as defined by the World Health Organization were effective in identifying patients with TB for the purposes of same-day antiretroviral therapy (ART) initiation in patients diagnosed with HIV, according to a pooled study of patients in two clinical trials. Guidelines suggest that patients with one or more TB symptoms be investigated for active TB before initiation of ART.
However, more than 80% of patients with TB symptoms did not have the disease and faced a delay of ART initiation, despite the many benefits of same-day ART initiation, according to the study presented online at the Conference on Retroviruses & Opportunistic Infections. This year CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
In her presentation, Alana T. Brennan, PhD, of the Boston University School of Public Health discussed the pooled results of 834 patients in the SLATE (Simple Algorithm for Treatment Eligibility) I and SLATE II trials. These two trials, conducted in South Africa and Kenya, respectively, assessed two variations of a simplified algorithm for eligibility for same-day ART initiation.
A total of 834 patients at baseline reported any self-described symptoms of TB using the WHO four-symptom TB screen (cough, fever, weight loss, night sweats). Those patients with any TB symptoms were assessed by sputum samples. The outcomes were prevalence of TB symptoms, TB diagnosis, and treatment.
Among the 834 patients, 493 (60%) reported no symptoms; 215 (26%) reported one to two symptoms, and 120 (14%) reported three to four symptoms. Only 66% of the patients with one to two symptoms were tested for TB; 78% of the patients with three to four symptoms were tested. Of these, only 1% of the patients with one to two symptoms tested positive for TB, and only 2% of the patients with three to four symptoms tested positive, according to Dr. Brennan.
“More than 80% of patients with TB symptoms did not have TB, but faced delay in ART initiation. No same-day [ART] initiators reported adverse events, so we hope that there would be some reconsideration of the requirement of TB testing prior to ART initiation due to any symptom of TB. … A potential consideration of the severity of the symptoms a patient has is necessary,” Dr. Brennan concluded.
Dr. Brennan reported that there were no disclosures.
SOURCE: Brennan AT et al. CROI 2020, Abstract 720.
FROM CROI 2020
OSA increases odds of hospital readmission after COPD exacerbation
more than threefold, according to results from a single-center study published in CHEST.
Mario Naranjo, MD, and colleagues retrospectively examined data from Albert Einstein Medical Center in Philadelphia to assess the impact of OSA on hospital readmission within 30 days of discharge after treatment for a COPD exacerbation. Dr. Naranjo is affiliated with Johns Hopkins Medicine, Baltimore.
The researchers analyzed data from 238 patients admitted for COPD exacerbation between May 2017 and July 2018 who were screened for previously unrecognized and untreated OSA and underwent a high-resolution pulse-oximetry or portable sleep monitoring study. In all, 111 (46.6%) had OSA; 28.6% had mild OSA, 9.7% had moderate OSA, and 8.4% had severe OSA.
Most baseline characteristics were similar among patients with and without OSA, but patients with OSA had a greater mean body mass index (33.9 vs. 30.3 kg/m2) and were more likely to have comorbid heart failure (19.8% vs. 7.1%), compared with patients without OSA. In addition, the proportion of male patients was greater in the cohort with OSA (60.4% vs. 49.6%).
For patients with mild OSA (oxygen desaturation index [ODI] ≥ 5 and < 15/hour), the odds of 30-day readmission were 2.05 times higher, compared with patients without OSA (32.4% vs. 18.9%). With moderate OSA (ODI ≥ 15 and < 30/hour), the odds of 30-day readmission were 6.68 times higher (60.9% vs. 18.9%). For severe OSA (ODI ≥ 30/hour), the odds were 10.01 times higher (70.0% vs. 18.9%). “For combined OSA severity categories, the odds of 30-day readmission were 3.5 times higher,” said Dr. Naranjo and colleagues. In addition, 90- and 180-day readmission rates and 6-month mortality rates were higher among patients with OSA.
“These findings have important implications for the evaluation and care of patients admitted to the hospital for COPD exacerbations,” Dr. Naranjo and colleagues said. “Although the combination of COPD and OSA (also known as the “overlap syndrome”) in ambulatory settings has been shown to have worse outcomes in terms of COPD exacerbations and mortality, these findings have not been reported previously for hospitalized COPD patients.”
Greater degrees of nocturnal hypoxemia and hypercapnia, worse functional status, and daytime sleepiness and fatigue may contribute to the relationship between OSA and the likelihood of hospital readmission, according to the authors. A multicenter study is warranted to confirm the results, they said.
Dr. Naranjo had no conflicts of interest. Coauthors have received grants from ResMed, Dayzz, and the National Institutes of Health and consulted for Jazz Pharmaceuticals, Best Doctors, and ResMed. One author is a committee chair for the American Academy of Sleep Medicine.
SOURCE: Naranjo M et al. Chest. 2020 Apr 2. doi: 10.1016/j.chest.2020.03.036.
more than threefold, according to results from a single-center study published in CHEST.
Mario Naranjo, MD, and colleagues retrospectively examined data from Albert Einstein Medical Center in Philadelphia to assess the impact of OSA on hospital readmission within 30 days of discharge after treatment for a COPD exacerbation. Dr. Naranjo is affiliated with Johns Hopkins Medicine, Baltimore.
The researchers analyzed data from 238 patients admitted for COPD exacerbation between May 2017 and July 2018 who were screened for previously unrecognized and untreated OSA and underwent a high-resolution pulse-oximetry or portable sleep monitoring study. In all, 111 (46.6%) had OSA; 28.6% had mild OSA, 9.7% had moderate OSA, and 8.4% had severe OSA.
Most baseline characteristics were similar among patients with and without OSA, but patients with OSA had a greater mean body mass index (33.9 vs. 30.3 kg/m2) and were more likely to have comorbid heart failure (19.8% vs. 7.1%), compared with patients without OSA. In addition, the proportion of male patients was greater in the cohort with OSA (60.4% vs. 49.6%).
For patients with mild OSA (oxygen desaturation index [ODI] ≥ 5 and < 15/hour), the odds of 30-day readmission were 2.05 times higher, compared with patients without OSA (32.4% vs. 18.9%). With moderate OSA (ODI ≥ 15 and < 30/hour), the odds of 30-day readmission were 6.68 times higher (60.9% vs. 18.9%). For severe OSA (ODI ≥ 30/hour), the odds were 10.01 times higher (70.0% vs. 18.9%). “For combined OSA severity categories, the odds of 30-day readmission were 3.5 times higher,” said Dr. Naranjo and colleagues. In addition, 90- and 180-day readmission rates and 6-month mortality rates were higher among patients with OSA.
“These findings have important implications for the evaluation and care of patients admitted to the hospital for COPD exacerbations,” Dr. Naranjo and colleagues said. “Although the combination of COPD and OSA (also known as the “overlap syndrome”) in ambulatory settings has been shown to have worse outcomes in terms of COPD exacerbations and mortality, these findings have not been reported previously for hospitalized COPD patients.”
Greater degrees of nocturnal hypoxemia and hypercapnia, worse functional status, and daytime sleepiness and fatigue may contribute to the relationship between OSA and the likelihood of hospital readmission, according to the authors. A multicenter study is warranted to confirm the results, they said.
Dr. Naranjo had no conflicts of interest. Coauthors have received grants from ResMed, Dayzz, and the National Institutes of Health and consulted for Jazz Pharmaceuticals, Best Doctors, and ResMed. One author is a committee chair for the American Academy of Sleep Medicine.
SOURCE: Naranjo M et al. Chest. 2020 Apr 2. doi: 10.1016/j.chest.2020.03.036.
more than threefold, according to results from a single-center study published in CHEST.
Mario Naranjo, MD, and colleagues retrospectively examined data from Albert Einstein Medical Center in Philadelphia to assess the impact of OSA on hospital readmission within 30 days of discharge after treatment for a COPD exacerbation. Dr. Naranjo is affiliated with Johns Hopkins Medicine, Baltimore.
The researchers analyzed data from 238 patients admitted for COPD exacerbation between May 2017 and July 2018 who were screened for previously unrecognized and untreated OSA and underwent a high-resolution pulse-oximetry or portable sleep monitoring study. In all, 111 (46.6%) had OSA; 28.6% had mild OSA, 9.7% had moderate OSA, and 8.4% had severe OSA.
Most baseline characteristics were similar among patients with and without OSA, but patients with OSA had a greater mean body mass index (33.9 vs. 30.3 kg/m2) and were more likely to have comorbid heart failure (19.8% vs. 7.1%), compared with patients without OSA. In addition, the proportion of male patients was greater in the cohort with OSA (60.4% vs. 49.6%).
For patients with mild OSA (oxygen desaturation index [ODI] ≥ 5 and < 15/hour), the odds of 30-day readmission were 2.05 times higher, compared with patients without OSA (32.4% vs. 18.9%). With moderate OSA (ODI ≥ 15 and < 30/hour), the odds of 30-day readmission were 6.68 times higher (60.9% vs. 18.9%). For severe OSA (ODI ≥ 30/hour), the odds were 10.01 times higher (70.0% vs. 18.9%). “For combined OSA severity categories, the odds of 30-day readmission were 3.5 times higher,” said Dr. Naranjo and colleagues. In addition, 90- and 180-day readmission rates and 6-month mortality rates were higher among patients with OSA.
“These findings have important implications for the evaluation and care of patients admitted to the hospital for COPD exacerbations,” Dr. Naranjo and colleagues said. “Although the combination of COPD and OSA (also known as the “overlap syndrome”) in ambulatory settings has been shown to have worse outcomes in terms of COPD exacerbations and mortality, these findings have not been reported previously for hospitalized COPD patients.”
Greater degrees of nocturnal hypoxemia and hypercapnia, worse functional status, and daytime sleepiness and fatigue may contribute to the relationship between OSA and the likelihood of hospital readmission, according to the authors. A multicenter study is warranted to confirm the results, they said.
Dr. Naranjo had no conflicts of interest. Coauthors have received grants from ResMed, Dayzz, and the National Institutes of Health and consulted for Jazz Pharmaceuticals, Best Doctors, and ResMed. One author is a committee chair for the American Academy of Sleep Medicine.
SOURCE: Naranjo M et al. Chest. 2020 Apr 2. doi: 10.1016/j.chest.2020.03.036.
FROM CHEST
First protocol on how to use lung ultrasound to triage COVID-19
The first protocol for the use of lung ultrasound to quantitatively and reproducibly assess the degree of lung involvement in patients suspected of having COVID-19 infection has been published by a team of Italian experts with experience using the technology on the front line.
Particularly in Spain and Italy — where the pandemic has struck hardest in Europe — hard-pressed clinicians seeking to quickly understand whether patients with seemingly mild disease could be harboring more serious lung involvement have increasingly relied upon lung ultrasound in the emergency room.
Now Libertario Demi, PhD, head of the ultrasound laboratory, University of Trento, Italy, and colleagues have developed a protocol, published online March 30 in the Journal of Ultrasound Medicine, to standardize practice.
Their research, which builds on previous work by the team, offers broad agreement with industry-led algorithms and emphasizes the use of wireless, handheld ultrasound devices, ideally consisting of a separate probe and tablet, to make sterilization easy.
Firms such as the Butterfly Network, Phillips, Clarius, GE Healthcare, and Siemens are among numerous companies that produce one or more such devices, including some that are completely integrated.
Not Universally Accepted
However, lung ultrasound is not yet universally accepted as a tool for diagnosing pneumonia in the context of COVID-19 and triaging patients.
The National Health Service in England does not even mention lung ultrasound in its radiology decision tool for suspected COVID-19, specifying instead chest X-ray as the first-line diagnostic imaging tool, with CT scanning in equivocal cases.
But Giovanni Volpicelli, MD, University Hospital San Luigi Gonzaga, Turin, Italy, who has previously described his experience to Medscape Medical News, says many patients with COVID-19 in his hospital presented with a negative chest X-ray but were found to have interstitial pneumonia on lung ultrasound.
Moreover, while CT scan remains the gold standard, the risk of nosocomial infection is more easily controlled if patients do not have to be transported to the radiology department but remain in the emergency room and instead undergo lung ultrasound there, he stressed.
Experts Share Experience of Lung Ultrasound in COVID-19
In developing and publishing their protocol, Demi, senior author of the article, and other colleagues from the heavily affected cities of Northern Italy, say their aim is “to share our experience and to propose a standardization with respect to the use of lung ultrasound in the management of COVID-19 patients.”
They reviewed an anonymized database of around 60,000 ultrasound images of confirmed COVID-19 cases and reviewers were blinded to patients’ clinical backgrounds.
For image acquisition, the authors recommend scanning 14 areas in each patient for 10 seconds, making the scans intercostal to cover the widest possible surface area.
They advise the use of a single focal point on the pleural line, which they write, optimizes the beam shape for observing the lung surface.
The authors also urge that the mechanical index (MI) be kept low because high MIs sustained for long periods “may result in damaging the lung.”
They also stress that cosmetic filters and modalities such as harmonic imaging, contrast, doppler, and compounding should be avoided, alongside saturation phenomena.
What Constitutes Intermediate Disease?
Once the images have been taken, they are scored on a 0-3 scale for each of the 14 areas, with no weighting on any individual area.
A score of 0 is given when the pleural line is continuous and regular, with the presence of A-lines, denoting that the lungs are unaffected.
An area is given a score of 3 when the scan shows dense and largely extended white lung tissue, with or without consolidations, indicating severe disease.
At both ends of this spectrum, there is agreement between the Italian protocol and an algorithm developed by the Butterfly Network.
However, the two differ when it comes to scoring intermediate cases. On the Butterfly algorithm, the suggestion is to look for B-lines, caused by fluid and cellular infiltration into the interstitium, and to weigh that against the need for supplementary oxygen.
The Italian team, in contrast, says a score of 1 is given when the pleural line is indented, with vertical areas of white visible below.
A score of 2 is given when the pleural line is broken, with small to large areas of consolidation and associated areas of white below.
Demi told Medscape Medical News that they did not refer to B-lines in their protocol as their visibility depends entirely on the imaging frequency and the probe used.
“This means that scoring on B-lines, people with different machines would give completely different scores for the same patient.”
He continued: “We prefer to refer to horizontal and vertical artifacts, and provide an analysis of the patterns, which is related to the physics of the interactions between the ultrasound waves and lung surface.”
In response, Mike Stone, MD, Legacy Emanuel Medical Center, Portland, Oregon, and director of education at Butterfly, said there appears to be wide variation in lung findings that “may or may not correlate with the severity of symptoms.”
He told Medscape Medical News it is “hard to know exactly if someone with pure B-lines will progress to serious illness or if someone with some subpleural consolidations will do well.”
A Negative Ultrasound Is the Most Useful
Volpicelli believes that, in any case, any patient with an intermediate pattern will require further diagnosis, such as other imaging modalities and blood exams, and the real role of lung ultrasound is in assessing patients at either end of the spectrum.
“In other words, there are situations where lung ultrasound can be considered definitive,” he told Medscape Medical News. “For instance, if I see a patient with mild signs of the disease, just fever, and I perform lung ultrasound and see nothing, lung ultrasound rules out pneumonia.”
“This patient may have COVID-19 of course, but they do not have pneumonia, and they can be treated at home, awaiting the result of the swab test. And this is useful because you can reduce the burden in the emergency department.”
Volpicelli continued: “On the other hand, there are patients with acute respiratory failure in respiratory distress. If the lung ultrasound is normal, you can rule out COVID-19 and you need to use other diagnostic procedures to understand the problem.”
“This is also very important for us because it’s crucial to be able to remove the patient from the isolation area and perform CT scan, chest radiography, and all the other diagnostic tools that we need.”
Are Wireless Machines Needed? Not Necessarily
With regard to the use of wireless technology, the Italian team says that “in the setting of COVID-19, wireless probes and tablets represent the most appropriate ultrasound equipment” because they can “easily be wrapped in single-use plastic covers, reducing the risk of contamination,” and making sterilization easy.
Stone suggests that integrated portable devices, however, are no more likely to cause cross-contamination than separate probes and tablets, as they can fit within a sterile sheath as a single unit.
Volpicelli, for his part, doesn’t like what he sees as undue focus on wireless devices for lung ultrasound in the COVID-19 protocols.
He is concerned that recommending them as the best approach may be sending out the wrong message, which could be very “dangerous” as people may then think they cannot perform this screening with standard ultrasound machines.
For him, the issue of cross contamination with standard lung ultrasound machines is “nonexistent. Cleaning the machine is quite easy and I do it hundreds of times per week.”
He does acknowledge, however, that if the lung ultrasound is performed under certain circumstances, for example when a patient is using a continuous positive airway pressure (CPAP) machine, “the risk of having the machine contaminated is a little bit higher.”
“In these situations...we have a more intensive cleaning procedure to avoid cross-contamination.”
He stressed: “Not all centers have wireless machines, whereas a normal machine is usually in all hospitals.”
“The advantages of using lung ultrasound [in COVID-19] are too great to be limited by something that is not important in my opinion,” he concluded.
Stone is director of education at the Butterfly Network. No other conflicts of interest were declared.
This article first appeared on Medscape.com.
The first protocol for the use of lung ultrasound to quantitatively and reproducibly assess the degree of lung involvement in patients suspected of having COVID-19 infection has been published by a team of Italian experts with experience using the technology on the front line.
Particularly in Spain and Italy — where the pandemic has struck hardest in Europe — hard-pressed clinicians seeking to quickly understand whether patients with seemingly mild disease could be harboring more serious lung involvement have increasingly relied upon lung ultrasound in the emergency room.
Now Libertario Demi, PhD, head of the ultrasound laboratory, University of Trento, Italy, and colleagues have developed a protocol, published online March 30 in the Journal of Ultrasound Medicine, to standardize practice.
Their research, which builds on previous work by the team, offers broad agreement with industry-led algorithms and emphasizes the use of wireless, handheld ultrasound devices, ideally consisting of a separate probe and tablet, to make sterilization easy.
Firms such as the Butterfly Network, Phillips, Clarius, GE Healthcare, and Siemens are among numerous companies that produce one or more such devices, including some that are completely integrated.
Not Universally Accepted
However, lung ultrasound is not yet universally accepted as a tool for diagnosing pneumonia in the context of COVID-19 and triaging patients.
The National Health Service in England does not even mention lung ultrasound in its radiology decision tool for suspected COVID-19, specifying instead chest X-ray as the first-line diagnostic imaging tool, with CT scanning in equivocal cases.
But Giovanni Volpicelli, MD, University Hospital San Luigi Gonzaga, Turin, Italy, who has previously described his experience to Medscape Medical News, says many patients with COVID-19 in his hospital presented with a negative chest X-ray but were found to have interstitial pneumonia on lung ultrasound.
Moreover, while CT scan remains the gold standard, the risk of nosocomial infection is more easily controlled if patients do not have to be transported to the radiology department but remain in the emergency room and instead undergo lung ultrasound there, he stressed.
Experts Share Experience of Lung Ultrasound in COVID-19
In developing and publishing their protocol, Demi, senior author of the article, and other colleagues from the heavily affected cities of Northern Italy, say their aim is “to share our experience and to propose a standardization with respect to the use of lung ultrasound in the management of COVID-19 patients.”
They reviewed an anonymized database of around 60,000 ultrasound images of confirmed COVID-19 cases and reviewers were blinded to patients’ clinical backgrounds.
For image acquisition, the authors recommend scanning 14 areas in each patient for 10 seconds, making the scans intercostal to cover the widest possible surface area.
They advise the use of a single focal point on the pleural line, which they write, optimizes the beam shape for observing the lung surface.
The authors also urge that the mechanical index (MI) be kept low because high MIs sustained for long periods “may result in damaging the lung.”
They also stress that cosmetic filters and modalities such as harmonic imaging, contrast, doppler, and compounding should be avoided, alongside saturation phenomena.
What Constitutes Intermediate Disease?
Once the images have been taken, they are scored on a 0-3 scale for each of the 14 areas, with no weighting on any individual area.
A score of 0 is given when the pleural line is continuous and regular, with the presence of A-lines, denoting that the lungs are unaffected.
An area is given a score of 3 when the scan shows dense and largely extended white lung tissue, with or without consolidations, indicating severe disease.
At both ends of this spectrum, there is agreement between the Italian protocol and an algorithm developed by the Butterfly Network.
However, the two differ when it comes to scoring intermediate cases. On the Butterfly algorithm, the suggestion is to look for B-lines, caused by fluid and cellular infiltration into the interstitium, and to weigh that against the need for supplementary oxygen.
The Italian team, in contrast, says a score of 1 is given when the pleural line is indented, with vertical areas of white visible below.
A score of 2 is given when the pleural line is broken, with small to large areas of consolidation and associated areas of white below.
Demi told Medscape Medical News that they did not refer to B-lines in their protocol as their visibility depends entirely on the imaging frequency and the probe used.
“This means that scoring on B-lines, people with different machines would give completely different scores for the same patient.”
He continued: “We prefer to refer to horizontal and vertical artifacts, and provide an analysis of the patterns, which is related to the physics of the interactions between the ultrasound waves and lung surface.”
In response, Mike Stone, MD, Legacy Emanuel Medical Center, Portland, Oregon, and director of education at Butterfly, said there appears to be wide variation in lung findings that “may or may not correlate with the severity of symptoms.”
He told Medscape Medical News it is “hard to know exactly if someone with pure B-lines will progress to serious illness or if someone with some subpleural consolidations will do well.”
A Negative Ultrasound Is the Most Useful
Volpicelli believes that, in any case, any patient with an intermediate pattern will require further diagnosis, such as other imaging modalities and blood exams, and the real role of lung ultrasound is in assessing patients at either end of the spectrum.
“In other words, there are situations where lung ultrasound can be considered definitive,” he told Medscape Medical News. “For instance, if I see a patient with mild signs of the disease, just fever, and I perform lung ultrasound and see nothing, lung ultrasound rules out pneumonia.”
“This patient may have COVID-19 of course, but they do not have pneumonia, and they can be treated at home, awaiting the result of the swab test. And this is useful because you can reduce the burden in the emergency department.”
Volpicelli continued: “On the other hand, there are patients with acute respiratory failure in respiratory distress. If the lung ultrasound is normal, you can rule out COVID-19 and you need to use other diagnostic procedures to understand the problem.”
“This is also very important for us because it’s crucial to be able to remove the patient from the isolation area and perform CT scan, chest radiography, and all the other diagnostic tools that we need.”
Are Wireless Machines Needed? Not Necessarily
With regard to the use of wireless technology, the Italian team says that “in the setting of COVID-19, wireless probes and tablets represent the most appropriate ultrasound equipment” because they can “easily be wrapped in single-use plastic covers, reducing the risk of contamination,” and making sterilization easy.
Stone suggests that integrated portable devices, however, are no more likely to cause cross-contamination than separate probes and tablets, as they can fit within a sterile sheath as a single unit.
Volpicelli, for his part, doesn’t like what he sees as undue focus on wireless devices for lung ultrasound in the COVID-19 protocols.
He is concerned that recommending them as the best approach may be sending out the wrong message, which could be very “dangerous” as people may then think they cannot perform this screening with standard ultrasound machines.
For him, the issue of cross contamination with standard lung ultrasound machines is “nonexistent. Cleaning the machine is quite easy and I do it hundreds of times per week.”
He does acknowledge, however, that if the lung ultrasound is performed under certain circumstances, for example when a patient is using a continuous positive airway pressure (CPAP) machine, “the risk of having the machine contaminated is a little bit higher.”
“In these situations...we have a more intensive cleaning procedure to avoid cross-contamination.”
He stressed: “Not all centers have wireless machines, whereas a normal machine is usually in all hospitals.”
“The advantages of using lung ultrasound [in COVID-19] are too great to be limited by something that is not important in my opinion,” he concluded.
Stone is director of education at the Butterfly Network. No other conflicts of interest were declared.
This article first appeared on Medscape.com.
The first protocol for the use of lung ultrasound to quantitatively and reproducibly assess the degree of lung involvement in patients suspected of having COVID-19 infection has been published by a team of Italian experts with experience using the technology on the front line.
Particularly in Spain and Italy — where the pandemic has struck hardest in Europe — hard-pressed clinicians seeking to quickly understand whether patients with seemingly mild disease could be harboring more serious lung involvement have increasingly relied upon lung ultrasound in the emergency room.
Now Libertario Demi, PhD, head of the ultrasound laboratory, University of Trento, Italy, and colleagues have developed a protocol, published online March 30 in the Journal of Ultrasound Medicine, to standardize practice.
Their research, which builds on previous work by the team, offers broad agreement with industry-led algorithms and emphasizes the use of wireless, handheld ultrasound devices, ideally consisting of a separate probe and tablet, to make sterilization easy.
Firms such as the Butterfly Network, Phillips, Clarius, GE Healthcare, and Siemens are among numerous companies that produce one or more such devices, including some that are completely integrated.
Not Universally Accepted
However, lung ultrasound is not yet universally accepted as a tool for diagnosing pneumonia in the context of COVID-19 and triaging patients.
The National Health Service in England does not even mention lung ultrasound in its radiology decision tool for suspected COVID-19, specifying instead chest X-ray as the first-line diagnostic imaging tool, with CT scanning in equivocal cases.
But Giovanni Volpicelli, MD, University Hospital San Luigi Gonzaga, Turin, Italy, who has previously described his experience to Medscape Medical News, says many patients with COVID-19 in his hospital presented with a negative chest X-ray but were found to have interstitial pneumonia on lung ultrasound.
Moreover, while CT scan remains the gold standard, the risk of nosocomial infection is more easily controlled if patients do not have to be transported to the radiology department but remain in the emergency room and instead undergo lung ultrasound there, he stressed.
Experts Share Experience of Lung Ultrasound in COVID-19
In developing and publishing their protocol, Demi, senior author of the article, and other colleagues from the heavily affected cities of Northern Italy, say their aim is “to share our experience and to propose a standardization with respect to the use of lung ultrasound in the management of COVID-19 patients.”
They reviewed an anonymized database of around 60,000 ultrasound images of confirmed COVID-19 cases and reviewers were blinded to patients’ clinical backgrounds.
For image acquisition, the authors recommend scanning 14 areas in each patient for 10 seconds, making the scans intercostal to cover the widest possible surface area.
They advise the use of a single focal point on the pleural line, which they write, optimizes the beam shape for observing the lung surface.
The authors also urge that the mechanical index (MI) be kept low because high MIs sustained for long periods “may result in damaging the lung.”
They also stress that cosmetic filters and modalities such as harmonic imaging, contrast, doppler, and compounding should be avoided, alongside saturation phenomena.
What Constitutes Intermediate Disease?
Once the images have been taken, they are scored on a 0-3 scale for each of the 14 areas, with no weighting on any individual area.
A score of 0 is given when the pleural line is continuous and regular, with the presence of A-lines, denoting that the lungs are unaffected.
An area is given a score of 3 when the scan shows dense and largely extended white lung tissue, with or without consolidations, indicating severe disease.
At both ends of this spectrum, there is agreement between the Italian protocol and an algorithm developed by the Butterfly Network.
However, the two differ when it comes to scoring intermediate cases. On the Butterfly algorithm, the suggestion is to look for B-lines, caused by fluid and cellular infiltration into the interstitium, and to weigh that against the need for supplementary oxygen.
The Italian team, in contrast, says a score of 1 is given when the pleural line is indented, with vertical areas of white visible below.
A score of 2 is given when the pleural line is broken, with small to large areas of consolidation and associated areas of white below.
Demi told Medscape Medical News that they did not refer to B-lines in their protocol as their visibility depends entirely on the imaging frequency and the probe used.
“This means that scoring on B-lines, people with different machines would give completely different scores for the same patient.”
He continued: “We prefer to refer to horizontal and vertical artifacts, and provide an analysis of the patterns, which is related to the physics of the interactions between the ultrasound waves and lung surface.”
In response, Mike Stone, MD, Legacy Emanuel Medical Center, Portland, Oregon, and director of education at Butterfly, said there appears to be wide variation in lung findings that “may or may not correlate with the severity of symptoms.”
He told Medscape Medical News it is “hard to know exactly if someone with pure B-lines will progress to serious illness or if someone with some subpleural consolidations will do well.”
A Negative Ultrasound Is the Most Useful
Volpicelli believes that, in any case, any patient with an intermediate pattern will require further diagnosis, such as other imaging modalities and blood exams, and the real role of lung ultrasound is in assessing patients at either end of the spectrum.
“In other words, there are situations where lung ultrasound can be considered definitive,” he told Medscape Medical News. “For instance, if I see a patient with mild signs of the disease, just fever, and I perform lung ultrasound and see nothing, lung ultrasound rules out pneumonia.”
“This patient may have COVID-19 of course, but they do not have pneumonia, and they can be treated at home, awaiting the result of the swab test. And this is useful because you can reduce the burden in the emergency department.”
Volpicelli continued: “On the other hand, there are patients with acute respiratory failure in respiratory distress. If the lung ultrasound is normal, you can rule out COVID-19 and you need to use other diagnostic procedures to understand the problem.”
“This is also very important for us because it’s crucial to be able to remove the patient from the isolation area and perform CT scan, chest radiography, and all the other diagnostic tools that we need.”
Are Wireless Machines Needed? Not Necessarily
With regard to the use of wireless technology, the Italian team says that “in the setting of COVID-19, wireless probes and tablets represent the most appropriate ultrasound equipment” because they can “easily be wrapped in single-use plastic covers, reducing the risk of contamination,” and making sterilization easy.
Stone suggests that integrated portable devices, however, are no more likely to cause cross-contamination than separate probes and tablets, as they can fit within a sterile sheath as a single unit.
Volpicelli, for his part, doesn’t like what he sees as undue focus on wireless devices for lung ultrasound in the COVID-19 protocols.
He is concerned that recommending them as the best approach may be sending out the wrong message, which could be very “dangerous” as people may then think they cannot perform this screening with standard ultrasound machines.
For him, the issue of cross contamination with standard lung ultrasound machines is “nonexistent. Cleaning the machine is quite easy and I do it hundreds of times per week.”
He does acknowledge, however, that if the lung ultrasound is performed under certain circumstances, for example when a patient is using a continuous positive airway pressure (CPAP) machine, “the risk of having the machine contaminated is a little bit higher.”
“In these situations...we have a more intensive cleaning procedure to avoid cross-contamination.”
He stressed: “Not all centers have wireless machines, whereas a normal machine is usually in all hospitals.”
“The advantages of using lung ultrasound [in COVID-19] are too great to be limited by something that is not important in my opinion,” he concluded.
Stone is director of education at the Butterfly Network. No other conflicts of interest were declared.
This article first appeared on Medscape.com.
FDA approves first generic albuterol inhaler
The Food and Drug Administration has approved the first generic of Proventil HFA (albuterol sulfate) metered-dose inhaler, 90 mcg/inhalation, according to a release from the agency. This inhaler is indicated for prevention of bronchospasm in patients aged 4 years and older. Specifically, these are patients with reversible obstructive airway disease or exercise-induced bronchospasm.
“The FDA recognizes the increased demand for albuterol products during the novel coronavirus pandemic,” said FDA Commissioner Stephen M. Hahn, MD.
The most common side effects include upper respiratory tract infection, rhinitis, nausea, vomiting, rapid heart rate, tremor, and nervousness.
This approval comes as part of FDA’s efforts to guide industry through the development process of generic products, according to the release. Complex combination products – such as this inhaler, which comprises both medication and a delivery system – can be more challenging to develop than solid oral dosage forms, such as tablets.
The FDA released a draft guidance in March 2020 specific to proposed generic albuterol sulfate metered-dose inhalers, including drug products referencing Proventil HFA. As with other similar guidances, it details the steps companies need to take in developing generics in order to submit complete applications for those products. The full news release regarding this approval is available on the FDA website.
This article was updated 4/8/20.
The Food and Drug Administration has approved the first generic of Proventil HFA (albuterol sulfate) metered-dose inhaler, 90 mcg/inhalation, according to a release from the agency. This inhaler is indicated for prevention of bronchospasm in patients aged 4 years and older. Specifically, these are patients with reversible obstructive airway disease or exercise-induced bronchospasm.
“The FDA recognizes the increased demand for albuterol products during the novel coronavirus pandemic,” said FDA Commissioner Stephen M. Hahn, MD.
The most common side effects include upper respiratory tract infection, rhinitis, nausea, vomiting, rapid heart rate, tremor, and nervousness.
This approval comes as part of FDA’s efforts to guide industry through the development process of generic products, according to the release. Complex combination products – such as this inhaler, which comprises both medication and a delivery system – can be more challenging to develop than solid oral dosage forms, such as tablets.
The FDA released a draft guidance in March 2020 specific to proposed generic albuterol sulfate metered-dose inhalers, including drug products referencing Proventil HFA. As with other similar guidances, it details the steps companies need to take in developing generics in order to submit complete applications for those products. The full news release regarding this approval is available on the FDA website.
This article was updated 4/8/20.
The Food and Drug Administration has approved the first generic of Proventil HFA (albuterol sulfate) metered-dose inhaler, 90 mcg/inhalation, according to a release from the agency. This inhaler is indicated for prevention of bronchospasm in patients aged 4 years and older. Specifically, these are patients with reversible obstructive airway disease or exercise-induced bronchospasm.
“The FDA recognizes the increased demand for albuterol products during the novel coronavirus pandemic,” said FDA Commissioner Stephen M. Hahn, MD.
The most common side effects include upper respiratory tract infection, rhinitis, nausea, vomiting, rapid heart rate, tremor, and nervousness.
This approval comes as part of FDA’s efforts to guide industry through the development process of generic products, according to the release. Complex combination products – such as this inhaler, which comprises both medication and a delivery system – can be more challenging to develop than solid oral dosage forms, such as tablets.
The FDA released a draft guidance in March 2020 specific to proposed generic albuterol sulfate metered-dose inhalers, including drug products referencing Proventil HFA. As with other similar guidances, it details the steps companies need to take in developing generics in order to submit complete applications for those products. The full news release regarding this approval is available on the FDA website.
This article was updated 4/8/20.
Comorbidities the rule in New York’s COVID-19 deaths
In New York state, just over 86% of reported COVID-19 deaths involved at least one comorbidity, according to the state’s department of health.
As of midnight on April 6, there had been 5,489 fatalities caused by COVID-19 in the state, of which 86.2% (4,732) had at least one underlying condition, the New York State Department of Health reported April 7 on its COVID-19 tracker.
The leading comorbidity, seen in 55.4% of all deaths, was hypertension. In comparison, a recent estimate from the U.S. Department of Health & Human Services put the prevalence of high blood pressure at about 45% in the overall adult population.
In New York, the rest of the 10 most common comorbidities in COVID-19 fatalities were diabetes (37.3%), hyperlipidemia (18.5%), coronary artery disease (12.4%), renal disease (11.0%), dementia (9.1%), chronic obstructive pulmonary disease (8.3%), cancer (8.1%), atrial fibrillation (7.1%), and heart failure (7.1%), the NYSDOH said.
Other data on the tracker site show that 63% of all deaths involved a patient who was aged 70 years or older and that 61% of COVID-19 patients who have died in New York were male and 38.8% were female (sex unknown for 0.2%). Among all individuals who have tested positive, 54.8% were male and 44.6% were female (sex unknown for 0.6%).
As of the end of day on April 6, a total of 340,058 persons had been tested in the state and 40.8% (138,863) were positive for the SARS-CoV-2 virus. By county, the highest positive rates are in New York City: Queens at 57.4%, Brooklyn at 52.4%, and the Bronx at 52.3%, according to the NYSDOH.
In New York state, just over 86% of reported COVID-19 deaths involved at least one comorbidity, according to the state’s department of health.
As of midnight on April 6, there had been 5,489 fatalities caused by COVID-19 in the state, of which 86.2% (4,732) had at least one underlying condition, the New York State Department of Health reported April 7 on its COVID-19 tracker.
The leading comorbidity, seen in 55.4% of all deaths, was hypertension. In comparison, a recent estimate from the U.S. Department of Health & Human Services put the prevalence of high blood pressure at about 45% in the overall adult population.
In New York, the rest of the 10 most common comorbidities in COVID-19 fatalities were diabetes (37.3%), hyperlipidemia (18.5%), coronary artery disease (12.4%), renal disease (11.0%), dementia (9.1%), chronic obstructive pulmonary disease (8.3%), cancer (8.1%), atrial fibrillation (7.1%), and heart failure (7.1%), the NYSDOH said.
Other data on the tracker site show that 63% of all deaths involved a patient who was aged 70 years or older and that 61% of COVID-19 patients who have died in New York were male and 38.8% were female (sex unknown for 0.2%). Among all individuals who have tested positive, 54.8% were male and 44.6% were female (sex unknown for 0.6%).
As of the end of day on April 6, a total of 340,058 persons had been tested in the state and 40.8% (138,863) were positive for the SARS-CoV-2 virus. By county, the highest positive rates are in New York City: Queens at 57.4%, Brooklyn at 52.4%, and the Bronx at 52.3%, according to the NYSDOH.
In New York state, just over 86% of reported COVID-19 deaths involved at least one comorbidity, according to the state’s department of health.
As of midnight on April 6, there had been 5,489 fatalities caused by COVID-19 in the state, of which 86.2% (4,732) had at least one underlying condition, the New York State Department of Health reported April 7 on its COVID-19 tracker.
The leading comorbidity, seen in 55.4% of all deaths, was hypertension. In comparison, a recent estimate from the U.S. Department of Health & Human Services put the prevalence of high blood pressure at about 45% in the overall adult population.
In New York, the rest of the 10 most common comorbidities in COVID-19 fatalities were diabetes (37.3%), hyperlipidemia (18.5%), coronary artery disease (12.4%), renal disease (11.0%), dementia (9.1%), chronic obstructive pulmonary disease (8.3%), cancer (8.1%), atrial fibrillation (7.1%), and heart failure (7.1%), the NYSDOH said.
Other data on the tracker site show that 63% of all deaths involved a patient who was aged 70 years or older and that 61% of COVID-19 patients who have died in New York were male and 38.8% were female (sex unknown for 0.2%). Among all individuals who have tested positive, 54.8% were male and 44.6% were female (sex unknown for 0.6%).
As of the end of day on April 6, a total of 340,058 persons had been tested in the state and 40.8% (138,863) were positive for the SARS-CoV-2 virus. By county, the highest positive rates are in New York City: Queens at 57.4%, Brooklyn at 52.4%, and the Bronx at 52.3%, according to the NYSDOH.
Superior turbinate eosinophilia predicts olfactory decline in patients with CRS
Olfactory decline in patients with chronic rhinosinusitis (CRS) after endoscopic sinus surgery is linked to superior turbinate eosinophilia, according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.
“,” Dawei Wu, MD, of Beijing Anzhen Hospital, Capital Medical University in Beijing, China, said in an interview.
There has been some research in the literature pointing to the link between CRS-associated olfactory dysfunction and superior turbinate eosinophilia. In a 2017 study, Lavin et al. found eosinophil markers in the superior turbinate tissue were elevated in patients with CRS with nasal polyps. One of the gene expressions of the eosinophil marker Charcot Leyden crystal protein (CLC) was inversely associated with olfactory threshold, which led the researchers to believe there was a link between olfactory decline and superior turbinate eosinophilia in these patients (Laryngoscope. 2017 Oct;127[10]:2210-2218).
Olfactory decline associated with CRS is the most common reason for loss of smell in ear, nose, and throat clinics, Dr. Wu said, but predicting this olfactory decline after endoscopic sinus surgery can be clinically challenging.
“The distinct feature of this smell disorder is the fluctuation in olfactory dysfunction which is mainly due to the recurrence of inflammation within the olfactory cleft. Notably, the level of eosinophils within the olfactory cleft significantly and positively correlated with the degree of olfactory dysfunction in patients with CRS both pre- and postoperatively,” he said.
Dr. Wu and colleagues conducted a prospective study to determine whether there was a link in CRS patients between preoperative superior turbinate eosinophilia and olfactory dysfunction after endoscopic sinus surgery. “We aimed to explore potential predictors of postoperative olfactory decline,” Dr. Wu said.
Overall, the investigators enrolled 78 patients with CRS in the study, where they received an olfactory assessment prior to and 3 months after endoscopic sinus surgery. The investigators used Sniffin’ Sticks (Burghardt; Wedel, Germany), a 12-item psychophysical smell test that uses everyday odors to conduct the olfactory assessment. If patients had a decrease in their threshold-discrimination-identification (TDI) score after surgery, they were determined to have olfactory deterioration. Prior to surgery, investigators measured olfactory cleft opacification using CT, with the olfactory cleft endoscopy scale used after surgery. The investigators also sampled patients’ superior turbinates at the time of surgery.
The results showed 23 of 78 patients (29.49%) had olfactory decline at 3 months after endoscopic sinus surgery. Those patients with olfactory decline had significantly higher tissue, blood eosinophil levels, and TDI scores before surgery, compared with patients with CRS who did not have any loss of smell. Patients with olfactory decline also had olfactory cleft opacification and olfactory cleft endoscopy scale scores, compared with patients who had no loss of smell after surgery.
One factor that predicted olfactory decline in these patients was an absolute count of 23.5 eosinophils per high-power field in the superior turbinate, researchers said (area under the ROC curve, 0.901). “Continuous elimination of the eosinophilic inflammation within the olfactory cleft in CRS patients with olfactory dysfunction may prevent the olfactory fluctuation after endoscopic sinus surgery,” Dr. Wu said.
Dr. Wu reports no relevant conflicts of interest.
SOURCE: Wu D et al. AAAAI. Abstract L7.
Olfactory decline in patients with chronic rhinosinusitis (CRS) after endoscopic sinus surgery is linked to superior turbinate eosinophilia, according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.
“,” Dawei Wu, MD, of Beijing Anzhen Hospital, Capital Medical University in Beijing, China, said in an interview.
There has been some research in the literature pointing to the link between CRS-associated olfactory dysfunction and superior turbinate eosinophilia. In a 2017 study, Lavin et al. found eosinophil markers in the superior turbinate tissue were elevated in patients with CRS with nasal polyps. One of the gene expressions of the eosinophil marker Charcot Leyden crystal protein (CLC) was inversely associated with olfactory threshold, which led the researchers to believe there was a link between olfactory decline and superior turbinate eosinophilia in these patients (Laryngoscope. 2017 Oct;127[10]:2210-2218).
Olfactory decline associated with CRS is the most common reason for loss of smell in ear, nose, and throat clinics, Dr. Wu said, but predicting this olfactory decline after endoscopic sinus surgery can be clinically challenging.
“The distinct feature of this smell disorder is the fluctuation in olfactory dysfunction which is mainly due to the recurrence of inflammation within the olfactory cleft. Notably, the level of eosinophils within the olfactory cleft significantly and positively correlated with the degree of olfactory dysfunction in patients with CRS both pre- and postoperatively,” he said.
Dr. Wu and colleagues conducted a prospective study to determine whether there was a link in CRS patients between preoperative superior turbinate eosinophilia and olfactory dysfunction after endoscopic sinus surgery. “We aimed to explore potential predictors of postoperative olfactory decline,” Dr. Wu said.
Overall, the investigators enrolled 78 patients with CRS in the study, where they received an olfactory assessment prior to and 3 months after endoscopic sinus surgery. The investigators used Sniffin’ Sticks (Burghardt; Wedel, Germany), a 12-item psychophysical smell test that uses everyday odors to conduct the olfactory assessment. If patients had a decrease in their threshold-discrimination-identification (TDI) score after surgery, they were determined to have olfactory deterioration. Prior to surgery, investigators measured olfactory cleft opacification using CT, with the olfactory cleft endoscopy scale used after surgery. The investigators also sampled patients’ superior turbinates at the time of surgery.
The results showed 23 of 78 patients (29.49%) had olfactory decline at 3 months after endoscopic sinus surgery. Those patients with olfactory decline had significantly higher tissue, blood eosinophil levels, and TDI scores before surgery, compared with patients with CRS who did not have any loss of smell. Patients with olfactory decline also had olfactory cleft opacification and olfactory cleft endoscopy scale scores, compared with patients who had no loss of smell after surgery.
One factor that predicted olfactory decline in these patients was an absolute count of 23.5 eosinophils per high-power field in the superior turbinate, researchers said (area under the ROC curve, 0.901). “Continuous elimination of the eosinophilic inflammation within the olfactory cleft in CRS patients with olfactory dysfunction may prevent the olfactory fluctuation after endoscopic sinus surgery,” Dr. Wu said.
Dr. Wu reports no relevant conflicts of interest.
SOURCE: Wu D et al. AAAAI. Abstract L7.
Olfactory decline in patients with chronic rhinosinusitis (CRS) after endoscopic sinus surgery is linked to superior turbinate eosinophilia, according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.
“,” Dawei Wu, MD, of Beijing Anzhen Hospital, Capital Medical University in Beijing, China, said in an interview.
There has been some research in the literature pointing to the link between CRS-associated olfactory dysfunction and superior turbinate eosinophilia. In a 2017 study, Lavin et al. found eosinophil markers in the superior turbinate tissue were elevated in patients with CRS with nasal polyps. One of the gene expressions of the eosinophil marker Charcot Leyden crystal protein (CLC) was inversely associated with olfactory threshold, which led the researchers to believe there was a link between olfactory decline and superior turbinate eosinophilia in these patients (Laryngoscope. 2017 Oct;127[10]:2210-2218).
Olfactory decline associated with CRS is the most common reason for loss of smell in ear, nose, and throat clinics, Dr. Wu said, but predicting this olfactory decline after endoscopic sinus surgery can be clinically challenging.
“The distinct feature of this smell disorder is the fluctuation in olfactory dysfunction which is mainly due to the recurrence of inflammation within the olfactory cleft. Notably, the level of eosinophils within the olfactory cleft significantly and positively correlated with the degree of olfactory dysfunction in patients with CRS both pre- and postoperatively,” he said.
Dr. Wu and colleagues conducted a prospective study to determine whether there was a link in CRS patients between preoperative superior turbinate eosinophilia and olfactory dysfunction after endoscopic sinus surgery. “We aimed to explore potential predictors of postoperative olfactory decline,” Dr. Wu said.
Overall, the investigators enrolled 78 patients with CRS in the study, where they received an olfactory assessment prior to and 3 months after endoscopic sinus surgery. The investigators used Sniffin’ Sticks (Burghardt; Wedel, Germany), a 12-item psychophysical smell test that uses everyday odors to conduct the olfactory assessment. If patients had a decrease in their threshold-discrimination-identification (TDI) score after surgery, they were determined to have olfactory deterioration. Prior to surgery, investigators measured olfactory cleft opacification using CT, with the olfactory cleft endoscopy scale used after surgery. The investigators also sampled patients’ superior turbinates at the time of surgery.
The results showed 23 of 78 patients (29.49%) had olfactory decline at 3 months after endoscopic sinus surgery. Those patients with olfactory decline had significantly higher tissue, blood eosinophil levels, and TDI scores before surgery, compared with patients with CRS who did not have any loss of smell. Patients with olfactory decline also had olfactory cleft opacification and olfactory cleft endoscopy scale scores, compared with patients who had no loss of smell after surgery.
One factor that predicted olfactory decline in these patients was an absolute count of 23.5 eosinophils per high-power field in the superior turbinate, researchers said (area under the ROC curve, 0.901). “Continuous elimination of the eosinophilic inflammation within the olfactory cleft in CRS patients with olfactory dysfunction may prevent the olfactory fluctuation after endoscopic sinus surgery,” Dr. Wu said.
Dr. Wu reports no relevant conflicts of interest.
SOURCE: Wu D et al. AAAAI. Abstract L7.
FROM AAAAI
A Veteran Presenting With Altered Mental Status and Clonus
►Zachary Reese, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC):Dr. Weller, the differential diagnosis for altered mental status is quite broad. How does the presence of clonus change or focus your approach to altered mental status?
►Jason Weller, MD, Instructor of Neurology, Boston Medical Center (BMC) and VABHS:The presence of clonus does not significantly narrow the differential. It does, however, suggest a central component to the patient’s altered mental status. Specifically, it implies that the underlying process, whether systemic or neurologic, interferes with central nervous system (CNS) control of the neuromuscular system.1 The differential is still quite broad and includes metabolic derangements (eg, uremia, electrolyte disturbances, hypercarbia, and thyroid dysfunction), medication toxicity from olanzapine or duloxetine, and vascular processes (eg, CNS vasculitis). Infectious etiologies, both within the CNS and systemically, can cause encephalopathy, as can autoimmune processes, such as immune-mediated encephalitis. Finally, primary neurologic conditions such as myoclonic epilepsy can be considered. Given the patient’s medical history, serotonin syndrome must be considered.
►Dr. Reese: Given the concern for serotonin syndrome, the admitting medical team discontinued the patient’s duloxetine. Dr. Weller, what is the pathophysiology of serotonin syndrome, and how is it diagnosed?
►Dr. Weller: Serotonin is ubiquitous throughout the body and brain. Serotonin syndrome is caused by excess endogenous or exogenous serotonin, and this is usually caused by a variety of medications. The symptoms range from tachycardia, agitation, and diaphoresis to sustained clonus, hyperthermia, and shock.2,3 The extent of serotonin syndrome is typically thought to reflect the degree of serotonergic activity.4
Serotonin syndrome is a clinical diagnosis. While there are no tests that can confirm the diagnosis, the Hunter criteria can be used to assist with making the diagnosis.5 Per the Hunter criteria, a patient can be diagnosed with serotonin syndrome if they have taken a serotonergic agent and have at least 1 of the following: spontaneous clonus, inducible or ocular clonus with agitation or diaphoresis, tremor and hyperreflexia, or hypertonia with fever and clonus. This patient had taken duloxetine and had inducible clonus and diaphoresis, thus suggesting a diagnosis of serotonin syndrome.
►Dr. Reese: Aside from selective serotonin reuptake inhibitors (SSRIs), are there other medications that we typically prescribe that can cause serotonin syndrome?
►Dr. Weller: In addition to SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs), other commonly prescribed medications that can cause serotonin syndrome are 5-HT3 antagonists (eg, ondansetron), 5-HT agonists (eg, triptans), and opioids (eg, fentanyl and tramadol). There are also case reports of atypical antipsychotics (eg, olanzapine) causing serotonin syndrome because of their antagonism of the 5-HT2 and 5-HT3 receptors.2 Additionally, linezolid is commonly overlooked as a cause of serotonin syndrome given its action as a monoamine oxidase inhibitor.4 In this patient, it would be prudent to discontinue olanzapine and duloxetine.
►Dr. Reese: Duloxetine, olanzapine, and buprenorphine/naloxone were discontinuedgiven concern for serotonin syndrome. Although there are not strong data that buprenorphine/ naloxone can cause serotonin syndrome, the team discontinued the medication in case it might be contributing to the patient’s encephalopathy, while closely monitoring the patient for withdrawal. There was a rapid improvement in the patient’s symptoms over the 24 hours after discontinuation of the 3 medications.
As part of the initial workup, the patient received a computed tomography (CT) scan of his chest to follow up pulmonary nodules identified 16 months prior. The CT scan showed interval growth of the pulmonary nodules in the right lower lobe to 2 cm with extension into the major fissure, which was concerning for malignancy. Plans were made for an outpatient positron emission tomography (PET) scan after hospital discharge.
Dr. Schlechter and Dr. Rangachari, what factors can help us determine whether or not further workup of a malignancy should occur before discharge or can be deferred to the outpatient setting?
►Benjamin Schlechter, MD, Instructor in Medicine, BIDMC; and Deepa Rangachari, MD, Assistant Professor of Medicine, BIDMC: Key considerations in this domain include rapidity of growth and any threat to critical end-organ function (ie, brain, heart, lungs, kidney, and liver). If the malignancy is bulky and/or rapidly progressing to the point that the patient has significant symptoms burden and/or end-organ dysfunction, then initiating the evaluation as an inpatient may be necessary. For suspected intrathoracic malignancies, considering whether this may be a high-grade process (ie, small cell lung cancer) is often a vital branch point. Key considerations in this regard are the following: Is it a bulky central tumor? Is there evidence of widespread metastatic disease, an obstructing mass, and/or tumor lysis? One final and critical aspect to consider is whether there are any patient- specific barriers to timely and reliable outpatient follow-up. If there is no evidence of rapid progression, bulky disease with threatened end-organ involvement, and/or issues with timely and reliable follow-up, then outpatient evaluation is often the best approach to ensure a comprehensive and well-coordinated effort on the patient’s behalf.
►Dr. Reese: Buprenorphine/naloxone was restarted without return of the symptoms. The patient was discharged home with an outpatient PET scan scheduled the following week. Unfortunately, the patient was unable to keep this appointment. Three weeks after hospital discharge, the patient presented again to the emergency department with gradually worsening altered mental status, confusion, visual hallucinations, and myoclonic jerking of the arms and legs. Medication adherence was confirmed by the patient’s wife, resulting in a low concern for serotonin syndrome. Physical examination revealed confusion, dysarthria, diffuse, arrhythmic, myoclonic jerking in all extremities, asterixis in the upper extremities, and hyperreflexia.
A CT scan of the brain did not reveal an intracranial process. A spot electroencephalograph (EEG) and magnetic resonance image (MRI) of the brain were obtained. Dr. Weller, what is the utility of spot EEG vs 24-hour EEG? When might we choose one over the other?
►Dr. Weller: If a patient is persistently altered, then a spot EEG would be sufficient to capture a seizure if that is what is causing the patient’s altered mental status. However, if the patient’s mental status is waxing and waning, then that may warrant a 24-hour EEG because the patient may need to be monitored for longer periods to capture an event that is causing intermittent alterations in mental status.6 Additionally, patients who are acutely ill may require long-term monitoring for the purpose of treatment and outcome management.
►Dr. Reese: The spot EEG showed nearly continuous generalized slowing indicative of a diffuse encephalopathy. The MRI of the brain showed scattered, nonspecific periventricular T2 hyperintense foci, suggestive of advanced chronic microvascular ischemic changes.
A PET CT was obtained and revealed mildly fluorodeoxyglucose (FDG)-avid, enlarging nodules within the right lower lobe, which was suspicious for malignancy. There were no other areas of FDG avidity on the PET scan. Valproic acid was initiated for treatment of myoclonus with transition to clonazepam when no improvement was seen. After starting clonazepam, the patient’s condition stabilized.
Dr. Weller, given the additional history, how has your differential diagnosis changed?
►Dr. Weller: Given the patient’s laboratory findings, we can be quite sure that there is not a contributing metabolic process. The findings suggestive of metastatic cancer, along with the profound neurologic changes, are most concerning for a paraneoplastic syndrome. I would suggest biopsy and consideration of a lumbar puncture. One can also send serum markers, including a paraneoplastic antibody panel.
►Dr. Reese: Biopsy of the mass in his right lower lobe revealed squamous cell lung cancer. Dr. Schlechter and Dr. Rangachari, do you have a framework for the different forms of lung cancer?
►Dr. Schlechter/Dr. Rangachari: The 2 broad categories of lung cancer are small cell and non-small cell (NSCLC). Small cell lung cancer has a tight association with tobacco exposure and is often clinically defined by rapid, bulky progression (ie, weeks to months).7,8 NSCLCs are also commonly seen in those with tobacco exposure, though not always. The main subgroups in this category are adenocarcinoma and squamous cell carcinoma. These cancers often evolve at a slower pace (ie, months to years).8 While small cell lung cancers are highgrade tumors and exquisitely sensitive to chemotherapy and radiation, NSCLCs tend to be less responsive to such therapies. The staging evaluation for either entity is the same and consists of defining localized vs metastatic disease.
►Dr. Reese: Because this patient had an MRI and PET scan that were both negative for metastatic disease, can we assume that this patient had stage I NSCLC?
►Dr. Schlechter/Dr. Rangachari: Not necessarily. While PET and MRI brain are exceptionally helpful in detecting distant metastases, they may over- or underestimate intrathoracic lymph node involvement by as much as 20%.9 As such, dedicated lymph node staging—either via bronchoscopy (endobronchial ultrasound) or surgically (mediastinoscopy) is indicated as lymph node involvement can significantly alter the stage, prognosis, and optimal therapeutic approach.10,11
►Dr. Reese: After this diagnosis was made, the teams caring for this patient attributed his altered mental status to a paraneoplastic syndrome. What is a paraneoplastic syndrome, and how does a paraneoplastic syndrome from malignancy present? Does its presence worsen a patient’s prognosis?
►Dr. Schlechter/Dr. Rangachari: A paraneoplastic syndrome is defined by an immunologic response to the cancer that ends up erroneously targeting self-antigens. Paraneoplastic syndromes are associated with a broad array of clinical findings—from endocrinopathy to encephalopathy—and certain neoplasms are more commonly associated with these syndromes than others (eg, small cell lung cancer and thymoma). Further, severity and onset of a paraneoplastic syndrome does not correlate with the burden of visible disease—and the syndrome may predate the cancer diagnosis by months to years.11 While treatment of the cancer affords the best hope of resolving the paraneoplastic syndrome, the cancer and the paraneoplastic process may have a discordant trajectory, with the paraneoplastic syndrome persisting even after the cancer is maximally treated. Although one might assume that paraneoplastic syndromes portend worse outcomes, in some cases, a presentation with the paraneoplastic syndrome may afford sooner detection of an otherwise occult/asymptomatic malignancy.
►Dr. Reese: The following week, the serum paraneoplastic antibody panel that tested for anti-Yo antibody, anti-Ri antibody,and anti-Hu antibody came back negative. Dr. Weller, what does this mean? Since we have yet to obtain a lumbar puncture, might his symptoms still be caused by a paraneoplastic syndrome?
►Dr. Weller: The negative serum test just means that he does not have antibodies to those 3 antibodies. There are now over 30 different paraneoplastic antibodies that have been discovered, and there are always more that are being discovered. So this negative test result does not exclude a paraneoplastic syndrome in the appropriate clinical context.12 Furthermore, the sensitivity and specificity for certain antibodies are different based upon source fluid, and cerebrospinal fluid testing would provide more diagnostic clarity. A negative test for paraneoplastic syndrome, by itself, would similarly not exclude a paraneoplastic syndrome. Often, empiric treatment is the best diagnostic option for paraneoplastic and autoimmune encephalopathies.
►Dr. Reese: The following week, the patient was discharged to rehabilitation with clonazepam for his symptoms and a scheduled follow-up. Given the patient’s frailty and medical comorbidities, thoracic surgery recommended consultation with radiation oncology. Dr. Schlechter and Dr. Rangachari, when do we decide to use radiation vs chemotherapy for someone with lung cancer?
►Dr. Schlechter/Dr. Rangachari: Patients with early stage, nonmetastatic NSCLC may not always be candidates for surgical resection on the basis of pulmonary function, other medical comorbidities (as in this case), anatomic considerations, and/or patient preference. In these cases, if there is lung-limited disease without lymph node involvement (ie, stage I/II NSCLC) and the patient is not felt to be an operative candidate, then alternatives to surgery include either radiation or ablation.13,14 As we care for an aging and comorbid population, evolving evidence suggests that well-selected patients with early stage disease undergoing these nonoperative approaches have roughly equivalent outcomes to those undergoing conventional surgical resection.13 In such cases, multidisciplinary consultation with a team having dedicated expertise in these various operative and nonoperative modalities is essential.
►Dr. Reese: The patient followed up with radiation oncology for consideration of radiation treatment, but his simulation CT scan showed some ground-glass opacity that were concerning for inflammation vs infection. The patient’s case was discussed at the multidisciplinary tumor board, and it was determined to treat him with antibiotics for a possible pneumonia before proceeding with radiation therapy. After he completed antibiotic treatment, he underwent 10 fractions of radiation treatment, which he tolerated well.
1. Kojovic M, Cordivari C, Bhatia K. Myoclonic disorders: a practical approach for diagnosis and treatment. Ther Adv Neurol Disord. 2011;4(1):47-62.
2. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013;13(4):533-540.
3. Arora B, Kannikeswaran N. The serotonin syndrome-the need for physician’s awareness. Int J Emerg Med. 2010;3(4):373-377.
4. Boyer EW, Shannon M. The serotonin syndrome [published correction appears in N Engl J Med. 2007;356(23):2437 and N Engl J Med. 2009;361(17):1714]. N Engl J Med.
2005;352(11):1112-1120.
5. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM.
2003;96(9):635-642.
6. Nordli DR Jr. Usefulness of video-EEG monitoring. Epilepsia. 2006;47(suppl 1):26-30.
7. Ettinger DS, Aisner J. Changing face of small-cell lung cancer: real and artifact. J Clin Oncol. 2006;24(28):4526-4527.
8. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243-1260.
9. Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of patients with NSCLC: a prospective trial. Ann Thorac Surg. 2005;80(4):1207-1214.
10. El-Osta H, Jani P, Mansour A, Rascoe P, Jafri S. Endobronchial ultrasound for nodal staging of patients with non-smallcell lung cancer with radiologically normal mediastinum. A meta-analysis. Ann Am Thorac Soc. 2018;15(7):864-874.
11. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(16):1543-1554.
12. McKeon A. Autoimmune Encephalopathies and Dementias. Continuum (Minneap Minn). 2016;22(2 Dementia): 538-558.
13. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Nonsmall cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584-594.
14. Ettinger DS, Aisner DL, Wood DE, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018. J Natl Compr Canc Netw. 2018;16(7):807-821.
►Zachary Reese, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC):Dr. Weller, the differential diagnosis for altered mental status is quite broad. How does the presence of clonus change or focus your approach to altered mental status?
►Jason Weller, MD, Instructor of Neurology, Boston Medical Center (BMC) and VABHS:The presence of clonus does not significantly narrow the differential. It does, however, suggest a central component to the patient’s altered mental status. Specifically, it implies that the underlying process, whether systemic or neurologic, interferes with central nervous system (CNS) control of the neuromuscular system.1 The differential is still quite broad and includes metabolic derangements (eg, uremia, electrolyte disturbances, hypercarbia, and thyroid dysfunction), medication toxicity from olanzapine or duloxetine, and vascular processes (eg, CNS vasculitis). Infectious etiologies, both within the CNS and systemically, can cause encephalopathy, as can autoimmune processes, such as immune-mediated encephalitis. Finally, primary neurologic conditions such as myoclonic epilepsy can be considered. Given the patient’s medical history, serotonin syndrome must be considered.
►Dr. Reese: Given the concern for serotonin syndrome, the admitting medical team discontinued the patient’s duloxetine. Dr. Weller, what is the pathophysiology of serotonin syndrome, and how is it diagnosed?
►Dr. Weller: Serotonin is ubiquitous throughout the body and brain. Serotonin syndrome is caused by excess endogenous or exogenous serotonin, and this is usually caused by a variety of medications. The symptoms range from tachycardia, agitation, and diaphoresis to sustained clonus, hyperthermia, and shock.2,3 The extent of serotonin syndrome is typically thought to reflect the degree of serotonergic activity.4
Serotonin syndrome is a clinical diagnosis. While there are no tests that can confirm the diagnosis, the Hunter criteria can be used to assist with making the diagnosis.5 Per the Hunter criteria, a patient can be diagnosed with serotonin syndrome if they have taken a serotonergic agent and have at least 1 of the following: spontaneous clonus, inducible or ocular clonus with agitation or diaphoresis, tremor and hyperreflexia, or hypertonia with fever and clonus. This patient had taken duloxetine and had inducible clonus and diaphoresis, thus suggesting a diagnosis of serotonin syndrome.
►Dr. Reese: Aside from selective serotonin reuptake inhibitors (SSRIs), are there other medications that we typically prescribe that can cause serotonin syndrome?
►Dr. Weller: In addition to SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs), other commonly prescribed medications that can cause serotonin syndrome are 5-HT3 antagonists (eg, ondansetron), 5-HT agonists (eg, triptans), and opioids (eg, fentanyl and tramadol). There are also case reports of atypical antipsychotics (eg, olanzapine) causing serotonin syndrome because of their antagonism of the 5-HT2 and 5-HT3 receptors.2 Additionally, linezolid is commonly overlooked as a cause of serotonin syndrome given its action as a monoamine oxidase inhibitor.4 In this patient, it would be prudent to discontinue olanzapine and duloxetine.
►Dr. Reese: Duloxetine, olanzapine, and buprenorphine/naloxone were discontinuedgiven concern for serotonin syndrome. Although there are not strong data that buprenorphine/ naloxone can cause serotonin syndrome, the team discontinued the medication in case it might be contributing to the patient’s encephalopathy, while closely monitoring the patient for withdrawal. There was a rapid improvement in the patient’s symptoms over the 24 hours after discontinuation of the 3 medications.
As part of the initial workup, the patient received a computed tomography (CT) scan of his chest to follow up pulmonary nodules identified 16 months prior. The CT scan showed interval growth of the pulmonary nodules in the right lower lobe to 2 cm with extension into the major fissure, which was concerning for malignancy. Plans were made for an outpatient positron emission tomography (PET) scan after hospital discharge.
Dr. Schlechter and Dr. Rangachari, what factors can help us determine whether or not further workup of a malignancy should occur before discharge or can be deferred to the outpatient setting?
►Benjamin Schlechter, MD, Instructor in Medicine, BIDMC; and Deepa Rangachari, MD, Assistant Professor of Medicine, BIDMC: Key considerations in this domain include rapidity of growth and any threat to critical end-organ function (ie, brain, heart, lungs, kidney, and liver). If the malignancy is bulky and/or rapidly progressing to the point that the patient has significant symptoms burden and/or end-organ dysfunction, then initiating the evaluation as an inpatient may be necessary. For suspected intrathoracic malignancies, considering whether this may be a high-grade process (ie, small cell lung cancer) is often a vital branch point. Key considerations in this regard are the following: Is it a bulky central tumor? Is there evidence of widespread metastatic disease, an obstructing mass, and/or tumor lysis? One final and critical aspect to consider is whether there are any patient- specific barriers to timely and reliable outpatient follow-up. If there is no evidence of rapid progression, bulky disease with threatened end-organ involvement, and/or issues with timely and reliable follow-up, then outpatient evaluation is often the best approach to ensure a comprehensive and well-coordinated effort on the patient’s behalf.
►Dr. Reese: Buprenorphine/naloxone was restarted without return of the symptoms. The patient was discharged home with an outpatient PET scan scheduled the following week. Unfortunately, the patient was unable to keep this appointment. Three weeks after hospital discharge, the patient presented again to the emergency department with gradually worsening altered mental status, confusion, visual hallucinations, and myoclonic jerking of the arms and legs. Medication adherence was confirmed by the patient’s wife, resulting in a low concern for serotonin syndrome. Physical examination revealed confusion, dysarthria, diffuse, arrhythmic, myoclonic jerking in all extremities, asterixis in the upper extremities, and hyperreflexia.
A CT scan of the brain did not reveal an intracranial process. A spot electroencephalograph (EEG) and magnetic resonance image (MRI) of the brain were obtained. Dr. Weller, what is the utility of spot EEG vs 24-hour EEG? When might we choose one over the other?
►Dr. Weller: If a patient is persistently altered, then a spot EEG would be sufficient to capture a seizure if that is what is causing the patient’s altered mental status. However, if the patient’s mental status is waxing and waning, then that may warrant a 24-hour EEG because the patient may need to be monitored for longer periods to capture an event that is causing intermittent alterations in mental status.6 Additionally, patients who are acutely ill may require long-term monitoring for the purpose of treatment and outcome management.
►Dr. Reese: The spot EEG showed nearly continuous generalized slowing indicative of a diffuse encephalopathy. The MRI of the brain showed scattered, nonspecific periventricular T2 hyperintense foci, suggestive of advanced chronic microvascular ischemic changes.
A PET CT was obtained and revealed mildly fluorodeoxyglucose (FDG)-avid, enlarging nodules within the right lower lobe, which was suspicious for malignancy. There were no other areas of FDG avidity on the PET scan. Valproic acid was initiated for treatment of myoclonus with transition to clonazepam when no improvement was seen. After starting clonazepam, the patient’s condition stabilized.
Dr. Weller, given the additional history, how has your differential diagnosis changed?
►Dr. Weller: Given the patient’s laboratory findings, we can be quite sure that there is not a contributing metabolic process. The findings suggestive of metastatic cancer, along with the profound neurologic changes, are most concerning for a paraneoplastic syndrome. I would suggest biopsy and consideration of a lumbar puncture. One can also send serum markers, including a paraneoplastic antibody panel.
►Dr. Reese: Biopsy of the mass in his right lower lobe revealed squamous cell lung cancer. Dr. Schlechter and Dr. Rangachari, do you have a framework for the different forms of lung cancer?
►Dr. Schlechter/Dr. Rangachari: The 2 broad categories of lung cancer are small cell and non-small cell (NSCLC). Small cell lung cancer has a tight association with tobacco exposure and is often clinically defined by rapid, bulky progression (ie, weeks to months).7,8 NSCLCs are also commonly seen in those with tobacco exposure, though not always. The main subgroups in this category are adenocarcinoma and squamous cell carcinoma. These cancers often evolve at a slower pace (ie, months to years).8 While small cell lung cancers are highgrade tumors and exquisitely sensitive to chemotherapy and radiation, NSCLCs tend to be less responsive to such therapies. The staging evaluation for either entity is the same and consists of defining localized vs metastatic disease.
►Dr. Reese: Because this patient had an MRI and PET scan that were both negative for metastatic disease, can we assume that this patient had stage I NSCLC?
►Dr. Schlechter/Dr. Rangachari: Not necessarily. While PET and MRI brain are exceptionally helpful in detecting distant metastases, they may over- or underestimate intrathoracic lymph node involvement by as much as 20%.9 As such, dedicated lymph node staging—either via bronchoscopy (endobronchial ultrasound) or surgically (mediastinoscopy) is indicated as lymph node involvement can significantly alter the stage, prognosis, and optimal therapeutic approach.10,11
►Dr. Reese: After this diagnosis was made, the teams caring for this patient attributed his altered mental status to a paraneoplastic syndrome. What is a paraneoplastic syndrome, and how does a paraneoplastic syndrome from malignancy present? Does its presence worsen a patient’s prognosis?
►Dr. Schlechter/Dr. Rangachari: A paraneoplastic syndrome is defined by an immunologic response to the cancer that ends up erroneously targeting self-antigens. Paraneoplastic syndromes are associated with a broad array of clinical findings—from endocrinopathy to encephalopathy—and certain neoplasms are more commonly associated with these syndromes than others (eg, small cell lung cancer and thymoma). Further, severity and onset of a paraneoplastic syndrome does not correlate with the burden of visible disease—and the syndrome may predate the cancer diagnosis by months to years.11 While treatment of the cancer affords the best hope of resolving the paraneoplastic syndrome, the cancer and the paraneoplastic process may have a discordant trajectory, with the paraneoplastic syndrome persisting even after the cancer is maximally treated. Although one might assume that paraneoplastic syndromes portend worse outcomes, in some cases, a presentation with the paraneoplastic syndrome may afford sooner detection of an otherwise occult/asymptomatic malignancy.
►Dr. Reese: The following week, the serum paraneoplastic antibody panel that tested for anti-Yo antibody, anti-Ri antibody,and anti-Hu antibody came back negative. Dr. Weller, what does this mean? Since we have yet to obtain a lumbar puncture, might his symptoms still be caused by a paraneoplastic syndrome?
►Dr. Weller: The negative serum test just means that he does not have antibodies to those 3 antibodies. There are now over 30 different paraneoplastic antibodies that have been discovered, and there are always more that are being discovered. So this negative test result does not exclude a paraneoplastic syndrome in the appropriate clinical context.12 Furthermore, the sensitivity and specificity for certain antibodies are different based upon source fluid, and cerebrospinal fluid testing would provide more diagnostic clarity. A negative test for paraneoplastic syndrome, by itself, would similarly not exclude a paraneoplastic syndrome. Often, empiric treatment is the best diagnostic option for paraneoplastic and autoimmune encephalopathies.
►Dr. Reese: The following week, the patient was discharged to rehabilitation with clonazepam for his symptoms and a scheduled follow-up. Given the patient’s frailty and medical comorbidities, thoracic surgery recommended consultation with radiation oncology. Dr. Schlechter and Dr. Rangachari, when do we decide to use radiation vs chemotherapy for someone with lung cancer?
►Dr. Schlechter/Dr. Rangachari: Patients with early stage, nonmetastatic NSCLC may not always be candidates for surgical resection on the basis of pulmonary function, other medical comorbidities (as in this case), anatomic considerations, and/or patient preference. In these cases, if there is lung-limited disease without lymph node involvement (ie, stage I/II NSCLC) and the patient is not felt to be an operative candidate, then alternatives to surgery include either radiation or ablation.13,14 As we care for an aging and comorbid population, evolving evidence suggests that well-selected patients with early stage disease undergoing these nonoperative approaches have roughly equivalent outcomes to those undergoing conventional surgical resection.13 In such cases, multidisciplinary consultation with a team having dedicated expertise in these various operative and nonoperative modalities is essential.
►Dr. Reese: The patient followed up with radiation oncology for consideration of radiation treatment, but his simulation CT scan showed some ground-glass opacity that were concerning for inflammation vs infection. The patient’s case was discussed at the multidisciplinary tumor board, and it was determined to treat him with antibiotics for a possible pneumonia before proceeding with radiation therapy. After he completed antibiotic treatment, he underwent 10 fractions of radiation treatment, which he tolerated well.
►Zachary Reese, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC):Dr. Weller, the differential diagnosis for altered mental status is quite broad. How does the presence of clonus change or focus your approach to altered mental status?
►Jason Weller, MD, Instructor of Neurology, Boston Medical Center (BMC) and VABHS:The presence of clonus does not significantly narrow the differential. It does, however, suggest a central component to the patient’s altered mental status. Specifically, it implies that the underlying process, whether systemic or neurologic, interferes with central nervous system (CNS) control of the neuromuscular system.1 The differential is still quite broad and includes metabolic derangements (eg, uremia, electrolyte disturbances, hypercarbia, and thyroid dysfunction), medication toxicity from olanzapine or duloxetine, and vascular processes (eg, CNS vasculitis). Infectious etiologies, both within the CNS and systemically, can cause encephalopathy, as can autoimmune processes, such as immune-mediated encephalitis. Finally, primary neurologic conditions such as myoclonic epilepsy can be considered. Given the patient’s medical history, serotonin syndrome must be considered.
►Dr. Reese: Given the concern for serotonin syndrome, the admitting medical team discontinued the patient’s duloxetine. Dr. Weller, what is the pathophysiology of serotonin syndrome, and how is it diagnosed?
►Dr. Weller: Serotonin is ubiquitous throughout the body and brain. Serotonin syndrome is caused by excess endogenous or exogenous serotonin, and this is usually caused by a variety of medications. The symptoms range from tachycardia, agitation, and diaphoresis to sustained clonus, hyperthermia, and shock.2,3 The extent of serotonin syndrome is typically thought to reflect the degree of serotonergic activity.4
Serotonin syndrome is a clinical diagnosis. While there are no tests that can confirm the diagnosis, the Hunter criteria can be used to assist with making the diagnosis.5 Per the Hunter criteria, a patient can be diagnosed with serotonin syndrome if they have taken a serotonergic agent and have at least 1 of the following: spontaneous clonus, inducible or ocular clonus with agitation or diaphoresis, tremor and hyperreflexia, or hypertonia with fever and clonus. This patient had taken duloxetine and had inducible clonus and diaphoresis, thus suggesting a diagnosis of serotonin syndrome.
►Dr. Reese: Aside from selective serotonin reuptake inhibitors (SSRIs), are there other medications that we typically prescribe that can cause serotonin syndrome?
►Dr. Weller: In addition to SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs), other commonly prescribed medications that can cause serotonin syndrome are 5-HT3 antagonists (eg, ondansetron), 5-HT agonists (eg, triptans), and opioids (eg, fentanyl and tramadol). There are also case reports of atypical antipsychotics (eg, olanzapine) causing serotonin syndrome because of their antagonism of the 5-HT2 and 5-HT3 receptors.2 Additionally, linezolid is commonly overlooked as a cause of serotonin syndrome given its action as a monoamine oxidase inhibitor.4 In this patient, it would be prudent to discontinue olanzapine and duloxetine.
►Dr. Reese: Duloxetine, olanzapine, and buprenorphine/naloxone were discontinuedgiven concern for serotonin syndrome. Although there are not strong data that buprenorphine/ naloxone can cause serotonin syndrome, the team discontinued the medication in case it might be contributing to the patient’s encephalopathy, while closely monitoring the patient for withdrawal. There was a rapid improvement in the patient’s symptoms over the 24 hours after discontinuation of the 3 medications.
As part of the initial workup, the patient received a computed tomography (CT) scan of his chest to follow up pulmonary nodules identified 16 months prior. The CT scan showed interval growth of the pulmonary nodules in the right lower lobe to 2 cm with extension into the major fissure, which was concerning for malignancy. Plans were made for an outpatient positron emission tomography (PET) scan after hospital discharge.
Dr. Schlechter and Dr. Rangachari, what factors can help us determine whether or not further workup of a malignancy should occur before discharge or can be deferred to the outpatient setting?
►Benjamin Schlechter, MD, Instructor in Medicine, BIDMC; and Deepa Rangachari, MD, Assistant Professor of Medicine, BIDMC: Key considerations in this domain include rapidity of growth and any threat to critical end-organ function (ie, brain, heart, lungs, kidney, and liver). If the malignancy is bulky and/or rapidly progressing to the point that the patient has significant symptoms burden and/or end-organ dysfunction, then initiating the evaluation as an inpatient may be necessary. For suspected intrathoracic malignancies, considering whether this may be a high-grade process (ie, small cell lung cancer) is often a vital branch point. Key considerations in this regard are the following: Is it a bulky central tumor? Is there evidence of widespread metastatic disease, an obstructing mass, and/or tumor lysis? One final and critical aspect to consider is whether there are any patient- specific barriers to timely and reliable outpatient follow-up. If there is no evidence of rapid progression, bulky disease with threatened end-organ involvement, and/or issues with timely and reliable follow-up, then outpatient evaluation is often the best approach to ensure a comprehensive and well-coordinated effort on the patient’s behalf.
►Dr. Reese: Buprenorphine/naloxone was restarted without return of the symptoms. The patient was discharged home with an outpatient PET scan scheduled the following week. Unfortunately, the patient was unable to keep this appointment. Three weeks after hospital discharge, the patient presented again to the emergency department with gradually worsening altered mental status, confusion, visual hallucinations, and myoclonic jerking of the arms and legs. Medication adherence was confirmed by the patient’s wife, resulting in a low concern for serotonin syndrome. Physical examination revealed confusion, dysarthria, diffuse, arrhythmic, myoclonic jerking in all extremities, asterixis in the upper extremities, and hyperreflexia.
A CT scan of the brain did not reveal an intracranial process. A spot electroencephalograph (EEG) and magnetic resonance image (MRI) of the brain were obtained. Dr. Weller, what is the utility of spot EEG vs 24-hour EEG? When might we choose one over the other?
►Dr. Weller: If a patient is persistently altered, then a spot EEG would be sufficient to capture a seizure if that is what is causing the patient’s altered mental status. However, if the patient’s mental status is waxing and waning, then that may warrant a 24-hour EEG because the patient may need to be monitored for longer periods to capture an event that is causing intermittent alterations in mental status.6 Additionally, patients who are acutely ill may require long-term monitoring for the purpose of treatment and outcome management.
►Dr. Reese: The spot EEG showed nearly continuous generalized slowing indicative of a diffuse encephalopathy. The MRI of the brain showed scattered, nonspecific periventricular T2 hyperintense foci, suggestive of advanced chronic microvascular ischemic changes.
A PET CT was obtained and revealed mildly fluorodeoxyglucose (FDG)-avid, enlarging nodules within the right lower lobe, which was suspicious for malignancy. There were no other areas of FDG avidity on the PET scan. Valproic acid was initiated for treatment of myoclonus with transition to clonazepam when no improvement was seen. After starting clonazepam, the patient’s condition stabilized.
Dr. Weller, given the additional history, how has your differential diagnosis changed?
►Dr. Weller: Given the patient’s laboratory findings, we can be quite sure that there is not a contributing metabolic process. The findings suggestive of metastatic cancer, along with the profound neurologic changes, are most concerning for a paraneoplastic syndrome. I would suggest biopsy and consideration of a lumbar puncture. One can also send serum markers, including a paraneoplastic antibody panel.
►Dr. Reese: Biopsy of the mass in his right lower lobe revealed squamous cell lung cancer. Dr. Schlechter and Dr. Rangachari, do you have a framework for the different forms of lung cancer?
►Dr. Schlechter/Dr. Rangachari: The 2 broad categories of lung cancer are small cell and non-small cell (NSCLC). Small cell lung cancer has a tight association with tobacco exposure and is often clinically defined by rapid, bulky progression (ie, weeks to months).7,8 NSCLCs are also commonly seen in those with tobacco exposure, though not always. The main subgroups in this category are adenocarcinoma and squamous cell carcinoma. These cancers often evolve at a slower pace (ie, months to years).8 While small cell lung cancers are highgrade tumors and exquisitely sensitive to chemotherapy and radiation, NSCLCs tend to be less responsive to such therapies. The staging evaluation for either entity is the same and consists of defining localized vs metastatic disease.
►Dr. Reese: Because this patient had an MRI and PET scan that were both negative for metastatic disease, can we assume that this patient had stage I NSCLC?
►Dr. Schlechter/Dr. Rangachari: Not necessarily. While PET and MRI brain are exceptionally helpful in detecting distant metastases, they may over- or underestimate intrathoracic lymph node involvement by as much as 20%.9 As such, dedicated lymph node staging—either via bronchoscopy (endobronchial ultrasound) or surgically (mediastinoscopy) is indicated as lymph node involvement can significantly alter the stage, prognosis, and optimal therapeutic approach.10,11
►Dr. Reese: After this diagnosis was made, the teams caring for this patient attributed his altered mental status to a paraneoplastic syndrome. What is a paraneoplastic syndrome, and how does a paraneoplastic syndrome from malignancy present? Does its presence worsen a patient’s prognosis?
►Dr. Schlechter/Dr. Rangachari: A paraneoplastic syndrome is defined by an immunologic response to the cancer that ends up erroneously targeting self-antigens. Paraneoplastic syndromes are associated with a broad array of clinical findings—from endocrinopathy to encephalopathy—and certain neoplasms are more commonly associated with these syndromes than others (eg, small cell lung cancer and thymoma). Further, severity and onset of a paraneoplastic syndrome does not correlate with the burden of visible disease—and the syndrome may predate the cancer diagnosis by months to years.11 While treatment of the cancer affords the best hope of resolving the paraneoplastic syndrome, the cancer and the paraneoplastic process may have a discordant trajectory, with the paraneoplastic syndrome persisting even after the cancer is maximally treated. Although one might assume that paraneoplastic syndromes portend worse outcomes, in some cases, a presentation with the paraneoplastic syndrome may afford sooner detection of an otherwise occult/asymptomatic malignancy.
►Dr. Reese: The following week, the serum paraneoplastic antibody panel that tested for anti-Yo antibody, anti-Ri antibody,and anti-Hu antibody came back negative. Dr. Weller, what does this mean? Since we have yet to obtain a lumbar puncture, might his symptoms still be caused by a paraneoplastic syndrome?
►Dr. Weller: The negative serum test just means that he does not have antibodies to those 3 antibodies. There are now over 30 different paraneoplastic antibodies that have been discovered, and there are always more that are being discovered. So this negative test result does not exclude a paraneoplastic syndrome in the appropriate clinical context.12 Furthermore, the sensitivity and specificity for certain antibodies are different based upon source fluid, and cerebrospinal fluid testing would provide more diagnostic clarity. A negative test for paraneoplastic syndrome, by itself, would similarly not exclude a paraneoplastic syndrome. Often, empiric treatment is the best diagnostic option for paraneoplastic and autoimmune encephalopathies.
►Dr. Reese: The following week, the patient was discharged to rehabilitation with clonazepam for his symptoms and a scheduled follow-up. Given the patient’s frailty and medical comorbidities, thoracic surgery recommended consultation with radiation oncology. Dr. Schlechter and Dr. Rangachari, when do we decide to use radiation vs chemotherapy for someone with lung cancer?
►Dr. Schlechter/Dr. Rangachari: Patients with early stage, nonmetastatic NSCLC may not always be candidates for surgical resection on the basis of pulmonary function, other medical comorbidities (as in this case), anatomic considerations, and/or patient preference. In these cases, if there is lung-limited disease without lymph node involvement (ie, stage I/II NSCLC) and the patient is not felt to be an operative candidate, then alternatives to surgery include either radiation or ablation.13,14 As we care for an aging and comorbid population, evolving evidence suggests that well-selected patients with early stage disease undergoing these nonoperative approaches have roughly equivalent outcomes to those undergoing conventional surgical resection.13 In such cases, multidisciplinary consultation with a team having dedicated expertise in these various operative and nonoperative modalities is essential.
►Dr. Reese: The patient followed up with radiation oncology for consideration of radiation treatment, but his simulation CT scan showed some ground-glass opacity that were concerning for inflammation vs infection. The patient’s case was discussed at the multidisciplinary tumor board, and it was determined to treat him with antibiotics for a possible pneumonia before proceeding with radiation therapy. After he completed antibiotic treatment, he underwent 10 fractions of radiation treatment, which he tolerated well.
1. Kojovic M, Cordivari C, Bhatia K. Myoclonic disorders: a practical approach for diagnosis and treatment. Ther Adv Neurol Disord. 2011;4(1):47-62.
2. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013;13(4):533-540.
3. Arora B, Kannikeswaran N. The serotonin syndrome-the need for physician’s awareness. Int J Emerg Med. 2010;3(4):373-377.
4. Boyer EW, Shannon M. The serotonin syndrome [published correction appears in N Engl J Med. 2007;356(23):2437 and N Engl J Med. 2009;361(17):1714]. N Engl J Med.
2005;352(11):1112-1120.
5. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM.
2003;96(9):635-642.
6. Nordli DR Jr. Usefulness of video-EEG monitoring. Epilepsia. 2006;47(suppl 1):26-30.
7. Ettinger DS, Aisner J. Changing face of small-cell lung cancer: real and artifact. J Clin Oncol. 2006;24(28):4526-4527.
8. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243-1260.
9. Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of patients with NSCLC: a prospective trial. Ann Thorac Surg. 2005;80(4):1207-1214.
10. El-Osta H, Jani P, Mansour A, Rascoe P, Jafri S. Endobronchial ultrasound for nodal staging of patients with non-smallcell lung cancer with radiologically normal mediastinum. A meta-analysis. Ann Am Thorac Soc. 2018;15(7):864-874.
11. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(16):1543-1554.
12. McKeon A. Autoimmune Encephalopathies and Dementias. Continuum (Minneap Minn). 2016;22(2 Dementia): 538-558.
13. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Nonsmall cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584-594.
14. Ettinger DS, Aisner DL, Wood DE, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018. J Natl Compr Canc Netw. 2018;16(7):807-821.
1. Kojovic M, Cordivari C, Bhatia K. Myoclonic disorders: a practical approach for diagnosis and treatment. Ther Adv Neurol Disord. 2011;4(1):47-62.
2. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013;13(4):533-540.
3. Arora B, Kannikeswaran N. The serotonin syndrome-the need for physician’s awareness. Int J Emerg Med. 2010;3(4):373-377.
4. Boyer EW, Shannon M. The serotonin syndrome [published correction appears in N Engl J Med. 2007;356(23):2437 and N Engl J Med. 2009;361(17):1714]. N Engl J Med.
2005;352(11):1112-1120.
5. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM.
2003;96(9):635-642.
6. Nordli DR Jr. Usefulness of video-EEG monitoring. Epilepsia. 2006;47(suppl 1):26-30.
7. Ettinger DS, Aisner J. Changing face of small-cell lung cancer: real and artifact. J Clin Oncol. 2006;24(28):4526-4527.
8. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243-1260.
9. Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of patients with NSCLC: a prospective trial. Ann Thorac Surg. 2005;80(4):1207-1214.
10. El-Osta H, Jani P, Mansour A, Rascoe P, Jafri S. Endobronchial ultrasound for nodal staging of patients with non-smallcell lung cancer with radiologically normal mediastinum. A meta-analysis. Ann Am Thorac Soc. 2018;15(7):864-874.
11. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003;349(16):1543-1554.
12. McKeon A. Autoimmune Encephalopathies and Dementias. Continuum (Minneap Minn). 2016;22(2 Dementia): 538-558.
13. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Nonsmall cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584-594.
14. Ettinger DS, Aisner DL, Wood DE, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018. J Natl Compr Canc Netw. 2018;16(7):807-821.