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extacy
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A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.
A surge in PTSD may be the ‘new normal’
The prolonged and unique stresses imparted by the COVID-19 pandemic has many predicting a significant rise in mental health issues in the weeks, months, and years ahead.
To understand how health care workers can best get ahead of this emerging crisis within a crisis, Medscape Psychiatry editorial director Bret Stetka, MD, spoke with Sheila Rauch, PhD, who’s with the Department of Psychiatry and Behavioral Sciences at the Emory University, Atlanta. The director of Mental Health Research and Program Evaluation at the Atlanta VA Medical Center, Dr. Rauch has studied the effects of and best treatments for posttraumatic stress disorder (PTSD) and anxiety disorders over the past 20 years.
Are we going to see a PTSD or anxiety epidemic as a result of the pandemic?
First, I think it’s really important that we prepare for the worst but hope for the best. But I would expect that, given the high levels of stress, the impact on resources, and other factors, we are going to see a pretty significant mental health impact over time. This could be the new normal for a while. Some of that will be PTSD, but there will also be other things. I would suspect that the resulting increase in rates of depression, traumatic grief, and loss is probably going to be a significant issue for years to come.
What will the anxiety we see as a result of COVID-19 look like compared with that seen in past disasters, like 9/11?
Most disasters in recent history, like 9/11, are single incidents. Something horrible happened, it impacted people at different levels, and we were able to start putting the pieces back together right away. The prolonged nature of this pandemic makes it even more variable given that the impact is going to be extended over time.
We’re also going to see a lot more people with compound impact – people who’ve lost their jobs, loved ones, maybe even their homes. All of those financial and resource losses put people in a higher risk category for negative mental health outcomes.
Is this analogous to the prolonged trauma that can occur with military service during war?
There is some similarity there. Combat is kind of an overarching context in which people experience trauma and, much like this pandemic, may or may not have traumatic exposures during it.
We’re asking health care workers to actually be in a role similar to what we ask of our military: going into danger, sometimes even without proper protective equipment, in order to save the lives of others. That’s also something we need to be factoring in as we plan to support those people and their families.
This is an ongoing incident, but is there a time window we need to be particularly worried about for seeing spikes in anxiety and PTSD?
I think we’re going to see variability on that. PTSD is a disorder that’s related to a specific incident or a couple of incidents that are similar. It’s a memory that’s haunting you.
For instance, typically if you have a combat veteran who has PTSD, they’ve been exposed to the overarching context of combat but then they have specific memories that are stuck. If they don’t have PTSD about 3-6 months after those incidents happen, then we would expect that they will not develop it, or it’s much less common that they would.
Depression has a very different course. It’s more prolonged and tends to grow with time.
Are you already seeing increased symptoms in your patients?
This is pretty similar to what we see in combat veterans. They’ll often be unhappy with the leadership decisions that were made as they were being deployed.
We’re also seeing lots more anger, sadness, and isolation now. Especially over the past couple of weeks, we’ve seen a rise in things like people reaching out for help in our intakes because we’re still open and doing phone assessments and telehealth with veterans and the veterans program.
In terms of interventions for this, what should psychiatrists, psychologists, and other clinicians be thinking about?
Right now, the best thing that we can do as mental health providers for people affected by the trauma is provide crisis intervention for those saying they are a danger to themselves and others. That means providing coping strategies and support. It also means making sure people are taking breaks and taking care of themselves, taking that little bit of time off so that they can go back, fully recharged, to their jobs and really stay there.
As we move forward, it will be clearer whether people are going to naturally recover, which most people will. For those who are going to have ongoing problems with time, we need to be getting ready as a system and as a country for those long-term mental health issues that are going to be coming up. And when I say long-term, it means the next 1-3 months. We want to be providing preventive interventions, versions of prolonged exposure, and other things that have shown some help in preventing PTSD. Psychological first aid is helpful.
There’s also an app called COVID Coach that the National Center for PTSD has created. That features a lot of positive coping resources together in one source.
Then when we get to the middle of that point and beyond it, we need to be ready to provide those evidence-based interventions for PTSD, depression, panic disorder, and other issues that are going to come out of this current situation.
But we were already short-staffed as far as mental health resources in general across the country, and especially in rural areas. So that means finding ways to efficiently use what we have through potentially briefer versions of interventions, through primary care, mental health, and other staff.
In what ways can primary care providers help?
There are versions of prolonged exposure therapy for primary care. That’s one of my big areas of research – increasing access. That would be something that we need to be building, by training and embedding mental health providers in primary care settings so that they can help to accommodate the increased need for access that’s going to be showing up for the next, I would suspect, several years with the pandemic.
Is there evidence that a prior episode of PTSD or traumatic experience like combat influences a subsequent reaction to a trauma like this?
It depends on how they manage. Research suggests that veterans or other people who have experienced trauma and naturally recovered, or who have gotten good treatment and remitted from that issue, are probably at no higher risk. But people who have subsyndromal PTSD or depression, or who are still experiencing symptoms from a history of trauma exposure, are maybe at a higher risk of having problems over time.
Do you have any guidance for healthcare providers on how to approach the pandemic with their patients, and also on how they can look after their own mental health?
In talking to patients, make sure that they have what they need. Ask if they’ve thought through how they’re going to cope if things get harder for them.
For people who have preexisting mental health issues, I’m talking with them about whether things have gotten worse. If they’re at high risk for suicide, I’m checking in to make sure that they’ve got new plans and ways to connect with people to reduce isolation, keeping in mind the social distancing that we’re asked to engage in so that they can do that safely.
It’s important to check and see if they have had any losses, whether it’s a financial loss or a personal loss of people that they care about. Also have them think through ways to stay entertained, which tends to help manage their own anxiety.
Every coping strategy we outline for patients also applies to mental health professionals. However, you would add to it the real need to take time to recharge, to take breaks, time off. It can feel overwhelming and like you need to just keep going. But the more that you get stuck in that mode of overdoing it, the less effective you’re going to be in helping people and also the more likely that you’ll be at risk of perhaps being one of the people that needs help.
It’s also important to make sure you’re staying connected with family and friends virtually, in whatever ways you can safely do that with social distancing.
So take a break to watch some Netflix now and then?
Yes!
A version of this article originally appeared on Medscape.com.
The prolonged and unique stresses imparted by the COVID-19 pandemic has many predicting a significant rise in mental health issues in the weeks, months, and years ahead.
To understand how health care workers can best get ahead of this emerging crisis within a crisis, Medscape Psychiatry editorial director Bret Stetka, MD, spoke with Sheila Rauch, PhD, who’s with the Department of Psychiatry and Behavioral Sciences at the Emory University, Atlanta. The director of Mental Health Research and Program Evaluation at the Atlanta VA Medical Center, Dr. Rauch has studied the effects of and best treatments for posttraumatic stress disorder (PTSD) and anxiety disorders over the past 20 years.
Are we going to see a PTSD or anxiety epidemic as a result of the pandemic?
First, I think it’s really important that we prepare for the worst but hope for the best. But I would expect that, given the high levels of stress, the impact on resources, and other factors, we are going to see a pretty significant mental health impact over time. This could be the new normal for a while. Some of that will be PTSD, but there will also be other things. I would suspect that the resulting increase in rates of depression, traumatic grief, and loss is probably going to be a significant issue for years to come.
What will the anxiety we see as a result of COVID-19 look like compared with that seen in past disasters, like 9/11?
Most disasters in recent history, like 9/11, are single incidents. Something horrible happened, it impacted people at different levels, and we were able to start putting the pieces back together right away. The prolonged nature of this pandemic makes it even more variable given that the impact is going to be extended over time.
We’re also going to see a lot more people with compound impact – people who’ve lost their jobs, loved ones, maybe even their homes. All of those financial and resource losses put people in a higher risk category for negative mental health outcomes.
Is this analogous to the prolonged trauma that can occur with military service during war?
There is some similarity there. Combat is kind of an overarching context in which people experience trauma and, much like this pandemic, may or may not have traumatic exposures during it.
We’re asking health care workers to actually be in a role similar to what we ask of our military: going into danger, sometimes even without proper protective equipment, in order to save the lives of others. That’s also something we need to be factoring in as we plan to support those people and their families.
This is an ongoing incident, but is there a time window we need to be particularly worried about for seeing spikes in anxiety and PTSD?
I think we’re going to see variability on that. PTSD is a disorder that’s related to a specific incident or a couple of incidents that are similar. It’s a memory that’s haunting you.
For instance, typically if you have a combat veteran who has PTSD, they’ve been exposed to the overarching context of combat but then they have specific memories that are stuck. If they don’t have PTSD about 3-6 months after those incidents happen, then we would expect that they will not develop it, or it’s much less common that they would.
Depression has a very different course. It’s more prolonged and tends to grow with time.
Are you already seeing increased symptoms in your patients?
This is pretty similar to what we see in combat veterans. They’ll often be unhappy with the leadership decisions that were made as they were being deployed.
We’re also seeing lots more anger, sadness, and isolation now. Especially over the past couple of weeks, we’ve seen a rise in things like people reaching out for help in our intakes because we’re still open and doing phone assessments and telehealth with veterans and the veterans program.
In terms of interventions for this, what should psychiatrists, psychologists, and other clinicians be thinking about?
Right now, the best thing that we can do as mental health providers for people affected by the trauma is provide crisis intervention for those saying they are a danger to themselves and others. That means providing coping strategies and support. It also means making sure people are taking breaks and taking care of themselves, taking that little bit of time off so that they can go back, fully recharged, to their jobs and really stay there.
As we move forward, it will be clearer whether people are going to naturally recover, which most people will. For those who are going to have ongoing problems with time, we need to be getting ready as a system and as a country for those long-term mental health issues that are going to be coming up. And when I say long-term, it means the next 1-3 months. We want to be providing preventive interventions, versions of prolonged exposure, and other things that have shown some help in preventing PTSD. Psychological first aid is helpful.
There’s also an app called COVID Coach that the National Center for PTSD has created. That features a lot of positive coping resources together in one source.
Then when we get to the middle of that point and beyond it, we need to be ready to provide those evidence-based interventions for PTSD, depression, panic disorder, and other issues that are going to come out of this current situation.
But we were already short-staffed as far as mental health resources in general across the country, and especially in rural areas. So that means finding ways to efficiently use what we have through potentially briefer versions of interventions, through primary care, mental health, and other staff.
In what ways can primary care providers help?
There are versions of prolonged exposure therapy for primary care. That’s one of my big areas of research – increasing access. That would be something that we need to be building, by training and embedding mental health providers in primary care settings so that they can help to accommodate the increased need for access that’s going to be showing up for the next, I would suspect, several years with the pandemic.
Is there evidence that a prior episode of PTSD or traumatic experience like combat influences a subsequent reaction to a trauma like this?
It depends on how they manage. Research suggests that veterans or other people who have experienced trauma and naturally recovered, or who have gotten good treatment and remitted from that issue, are probably at no higher risk. But people who have subsyndromal PTSD or depression, or who are still experiencing symptoms from a history of trauma exposure, are maybe at a higher risk of having problems over time.
Do you have any guidance for healthcare providers on how to approach the pandemic with their patients, and also on how they can look after their own mental health?
In talking to patients, make sure that they have what they need. Ask if they’ve thought through how they’re going to cope if things get harder for them.
For people who have preexisting mental health issues, I’m talking with them about whether things have gotten worse. If they’re at high risk for suicide, I’m checking in to make sure that they’ve got new plans and ways to connect with people to reduce isolation, keeping in mind the social distancing that we’re asked to engage in so that they can do that safely.
It’s important to check and see if they have had any losses, whether it’s a financial loss or a personal loss of people that they care about. Also have them think through ways to stay entertained, which tends to help manage their own anxiety.
Every coping strategy we outline for patients also applies to mental health professionals. However, you would add to it the real need to take time to recharge, to take breaks, time off. It can feel overwhelming and like you need to just keep going. But the more that you get stuck in that mode of overdoing it, the less effective you’re going to be in helping people and also the more likely that you’ll be at risk of perhaps being one of the people that needs help.
It’s also important to make sure you’re staying connected with family and friends virtually, in whatever ways you can safely do that with social distancing.
So take a break to watch some Netflix now and then?
Yes!
A version of this article originally appeared on Medscape.com.
The prolonged and unique stresses imparted by the COVID-19 pandemic has many predicting a significant rise in mental health issues in the weeks, months, and years ahead.
To understand how health care workers can best get ahead of this emerging crisis within a crisis, Medscape Psychiatry editorial director Bret Stetka, MD, spoke with Sheila Rauch, PhD, who’s with the Department of Psychiatry and Behavioral Sciences at the Emory University, Atlanta. The director of Mental Health Research and Program Evaluation at the Atlanta VA Medical Center, Dr. Rauch has studied the effects of and best treatments for posttraumatic stress disorder (PTSD) and anxiety disorders over the past 20 years.
Are we going to see a PTSD or anxiety epidemic as a result of the pandemic?
First, I think it’s really important that we prepare for the worst but hope for the best. But I would expect that, given the high levels of stress, the impact on resources, and other factors, we are going to see a pretty significant mental health impact over time. This could be the new normal for a while. Some of that will be PTSD, but there will also be other things. I would suspect that the resulting increase in rates of depression, traumatic grief, and loss is probably going to be a significant issue for years to come.
What will the anxiety we see as a result of COVID-19 look like compared with that seen in past disasters, like 9/11?
Most disasters in recent history, like 9/11, are single incidents. Something horrible happened, it impacted people at different levels, and we were able to start putting the pieces back together right away. The prolonged nature of this pandemic makes it even more variable given that the impact is going to be extended over time.
We’re also going to see a lot more people with compound impact – people who’ve lost their jobs, loved ones, maybe even their homes. All of those financial and resource losses put people in a higher risk category for negative mental health outcomes.
Is this analogous to the prolonged trauma that can occur with military service during war?
There is some similarity there. Combat is kind of an overarching context in which people experience trauma and, much like this pandemic, may or may not have traumatic exposures during it.
We’re asking health care workers to actually be in a role similar to what we ask of our military: going into danger, sometimes even without proper protective equipment, in order to save the lives of others. That’s also something we need to be factoring in as we plan to support those people and their families.
This is an ongoing incident, but is there a time window we need to be particularly worried about for seeing spikes in anxiety and PTSD?
I think we’re going to see variability on that. PTSD is a disorder that’s related to a specific incident or a couple of incidents that are similar. It’s a memory that’s haunting you.
For instance, typically if you have a combat veteran who has PTSD, they’ve been exposed to the overarching context of combat but then they have specific memories that are stuck. If they don’t have PTSD about 3-6 months after those incidents happen, then we would expect that they will not develop it, or it’s much less common that they would.
Depression has a very different course. It’s more prolonged and tends to grow with time.
Are you already seeing increased symptoms in your patients?
This is pretty similar to what we see in combat veterans. They’ll often be unhappy with the leadership decisions that were made as they were being deployed.
We’re also seeing lots more anger, sadness, and isolation now. Especially over the past couple of weeks, we’ve seen a rise in things like people reaching out for help in our intakes because we’re still open and doing phone assessments and telehealth with veterans and the veterans program.
In terms of interventions for this, what should psychiatrists, psychologists, and other clinicians be thinking about?
Right now, the best thing that we can do as mental health providers for people affected by the trauma is provide crisis intervention for those saying they are a danger to themselves and others. That means providing coping strategies and support. It also means making sure people are taking breaks and taking care of themselves, taking that little bit of time off so that they can go back, fully recharged, to their jobs and really stay there.
As we move forward, it will be clearer whether people are going to naturally recover, which most people will. For those who are going to have ongoing problems with time, we need to be getting ready as a system and as a country for those long-term mental health issues that are going to be coming up. And when I say long-term, it means the next 1-3 months. We want to be providing preventive interventions, versions of prolonged exposure, and other things that have shown some help in preventing PTSD. Psychological first aid is helpful.
There’s also an app called COVID Coach that the National Center for PTSD has created. That features a lot of positive coping resources together in one source.
Then when we get to the middle of that point and beyond it, we need to be ready to provide those evidence-based interventions for PTSD, depression, panic disorder, and other issues that are going to come out of this current situation.
But we were already short-staffed as far as mental health resources in general across the country, and especially in rural areas. So that means finding ways to efficiently use what we have through potentially briefer versions of interventions, through primary care, mental health, and other staff.
In what ways can primary care providers help?
There are versions of prolonged exposure therapy for primary care. That’s one of my big areas of research – increasing access. That would be something that we need to be building, by training and embedding mental health providers in primary care settings so that they can help to accommodate the increased need for access that’s going to be showing up for the next, I would suspect, several years with the pandemic.
Is there evidence that a prior episode of PTSD or traumatic experience like combat influences a subsequent reaction to a trauma like this?
It depends on how they manage. Research suggests that veterans or other people who have experienced trauma and naturally recovered, or who have gotten good treatment and remitted from that issue, are probably at no higher risk. But people who have subsyndromal PTSD or depression, or who are still experiencing symptoms from a history of trauma exposure, are maybe at a higher risk of having problems over time.
Do you have any guidance for healthcare providers on how to approach the pandemic with their patients, and also on how they can look after their own mental health?
In talking to patients, make sure that they have what they need. Ask if they’ve thought through how they’re going to cope if things get harder for them.
For people who have preexisting mental health issues, I’m talking with them about whether things have gotten worse. If they’re at high risk for suicide, I’m checking in to make sure that they’ve got new plans and ways to connect with people to reduce isolation, keeping in mind the social distancing that we’re asked to engage in so that they can do that safely.
It’s important to check and see if they have had any losses, whether it’s a financial loss or a personal loss of people that they care about. Also have them think through ways to stay entertained, which tends to help manage their own anxiety.
Every coping strategy we outline for patients also applies to mental health professionals. However, you would add to it the real need to take time to recharge, to take breaks, time off. It can feel overwhelming and like you need to just keep going. But the more that you get stuck in that mode of overdoing it, the less effective you’re going to be in helping people and also the more likely that you’ll be at risk of perhaps being one of the people that needs help.
It’s also important to make sure you’re staying connected with family and friends virtually, in whatever ways you can safely do that with social distancing.
So take a break to watch some Netflix now and then?
Yes!
A version of this article originally appeared on Medscape.com.
Modify risk factors to manage ICU delirium in patients with COVID-19
, and a bedside risk management strategy based on modifiable risk factors can help prevent lingering effects on cognition, according to an article published in Critical Care.
Several factors can contribute to an increased risk of ICU delirium in COVID-19 patients, wrote Katarzyna Kotfis, MD, of Pomeranian Medical University, Szczecin, Poland, and colleagues.
“In patients with COVID-19, delirium may be a manifestation of direct central nervous system invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failure, an effect of sedative strategies, prolonged mechanical ventilation time, or environmental factors, including social isolation,” they said.
Delirium in the context of COVID-19 can mean an early sign of infection, so patients should be screened using dedicated psychometric tools, the researchers wrote. Also, COVID-19 has been shown to cause pneumonia in elderly patients, who are at high risk for severe pulmonary disease related to COVID-19 and for ICU delirium generally, they said.
In addition, don’t underestimate the impact of social isolation created by quarantines, the researchers said.
“What is needed now, is not only high-quality ICU care, concentrated on providing adequate respiratory support to critically ill patients, but an identification of the source and degree of mental and spiritual suffering of patients as well as their families to provide the most ethical and person-centered care during this humanitarian crisis,” they emphasized. However, they acknowledged that nonpharmacologic interventions such as mobility outside the ICU room and interactions with family members are limited by the COVID-19 situation.
The researchers noted several mechanisms by which the COVID-19 virus may cause brain damage, including through the dysfunction of the renin-angiotensin system.
“Inflammatory response of the CNS to viral infection seems to be another important reason for poor neurological outcome and occurrence of delirium,” in COVID-19 patients, they said.
As for risk-reduction strategies, the researchers noted that “delirium in mechanically ventilated patients can be reduced dramatically to 50% using a culture of lighter sedation and mobilization via the implementation of the safety bundle called the ABCDEFs promoted by the Society of Critical Care Medicine in their ICU Liberation Collaborative,” although COVID-19 isolation is a barrier, they said.
The ABCDEF bundle consists of Assessment of pain, Both spontaneous awakening trials and spontaneous breathing trials, Choice of sedation, Delirium (hyperactive or hypoactive), Early mobility, and Family presence; all of which are challenging in the COVID-19 environment, the researchers said.
They advised implementing easy screening methods for delirium to reduce the burden on medical staff, and emphasized the importance of regular patient orientation, despite social separation from family and caregivers.
“No drugs can be recommended for the prevention or treatment of ICU delirium other than avoidance of overuse of potent psychoactive agents like sedatives and neuromuscular blockers (NMB) unless patients absolutely require such management,” they added.
“Delirium is so common and so hard to manage in the COVID-19 population,” Mangala Narasimhan, DO, of Northwell Health in New Hyde Park, N.Y., said in an interview. Delirium is impacted by many sources including a viral encephalopathy, the amount and duration of sedation medications, and prolonged intubation and hypoxemia, she said. “Managing the delirium allows you to wake the patient up successfully and without a lot of discoordination. This will help with weaning,” she noted. Barriers to delirium management for COVID-19 patients include the length of time on a ventilator, as well as amount of sedatives and paralytics, and the added issues of renal insufficiency, she noted. “How they can be addressed is thoughtful plans on the addition of long-term sedation for withdrawal symptoms, and anxiolytics for the profound anxiety associated with arousal from this type of sedation on ventilators, she said. The take-home message for clinicians is the need to perform weaning trials to manage delirium in the ICU. “We have to combat this delirium in order to be successful in taking these patients off of ventilators,” she said. Dr. Narasimhan added that more research is needed on areas including drug-to-drug interactions, duration of efficacy of various drugs, and how the virus affects the brain.
“Adherence to the ABCDEF bundle can reduce the incidence of delirium, from approximately 75% of mechanically ventilated patients to 50% or less,” David L. Bowton, MD, of Wake Forest Baptist Health in Winston-Salem, N.C., said in an interview.
“Importantly, in most studies, bundle adherence reduces mortality and ICU length of stay and lowers the total cost of care. However, isolation of patients and protection of staff, visitor restrictions, and potentially stressed staffing will likely alter how most institutions approach bundle compliance,” he said. “Gathering input from infection control clinicians and bedside providers from multiple disciplines that consider these factors to critically examine current bundle procedures and workflow will be essential to the creation and/or revision of bundle processes of care that maintain the integrity of the ABCDEF bundle yet preserve staff, patient, and family safety,” he said.
“We did not have strong evidence to suggest an optimal approach to treating delirium before the advent of the COVID-19 pandemic, so I do not believe we know what the best approach is in the current environment,” Dr. Bowton added. “Further, vigilance will be necessary to ensure that altered consciousness or cognition is ICU delirium and not attributable to another cause such as drug withdrawal, drug adverse effect, or primary central nervous system infection or immune response that mandates specific therapy,” he emphasized.
For clinicians, “this study reminds us of the importance of the ABCDEF bundle to improve outcomes of critical illness,” said Dr. Bowton. “It highlights the difficulties of providing frequent reassessment of pain, comfort, reassurance, and reorientation to critically ill patients. To me, it underscores the importance of each institution critically examining staffing needs and staffing roles to mitigate these difficulties and to explore novel methods of maintaining staff-patient and family-patient interactions to enhance compliance with all elements of the ABCDEF bundle while maintaining the safety of staff and families.”
Dr. Bowton added, “When necessary, explicit modifications to existing ABCDEF bundles should be developed and disseminated to provide realistic, readily understood guidance to achieve the best possible compliance with each bundle element. One potentially underrecognized issue will be the large, hopefully temporary, number of people requiring post–critical illness rehabilitation and mental health services,” he said. “In many regions these services are already underfunded and ill-equipped to handle an increased demand for these services,” he noted.
Additional research is needed in many areas, said Dr. Bowton. “While compliance with the ABCDEF bundle decreases the incidence and duration of delirium, decreases ICU length of stay, decreases duration of mechanical ventilation, and improves mortality, many questions remain. Individual elements of the bundle have been inconsistently associated with improved outcomes,” he said. “What is the relative importance of specific elements and what are the mechanisms by which they improve outcomes?” he asked. “We still do not know how to best achieve physical/functional recovery following critical illness, which, in light of these authors’ studies relating persisting physical debility to depression (Lancet Respir Med. 2014; 2[5]:369-79), may be a key component to improving long-term outcomes,” he said.
The study received no specific funding, although several coauthors disclosed grants from agencies including the National Center for Advancing Translational Sciences, National Institute of General Medical Sciences, National Heart, Lung, and Blood Institute, and National Institute on Aging. Dr. Narasimhan and Dr. Bowton had no financial conflicts to disclose.
SOURCE: Kotfis K et al. Critical Care. 2020 Apr 28. doi: 10.1186/s13054-020-02882-x.
, and a bedside risk management strategy based on modifiable risk factors can help prevent lingering effects on cognition, according to an article published in Critical Care.
Several factors can contribute to an increased risk of ICU delirium in COVID-19 patients, wrote Katarzyna Kotfis, MD, of Pomeranian Medical University, Szczecin, Poland, and colleagues.
“In patients with COVID-19, delirium may be a manifestation of direct central nervous system invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failure, an effect of sedative strategies, prolonged mechanical ventilation time, or environmental factors, including social isolation,” they said.
Delirium in the context of COVID-19 can mean an early sign of infection, so patients should be screened using dedicated psychometric tools, the researchers wrote. Also, COVID-19 has been shown to cause pneumonia in elderly patients, who are at high risk for severe pulmonary disease related to COVID-19 and for ICU delirium generally, they said.
In addition, don’t underestimate the impact of social isolation created by quarantines, the researchers said.
“What is needed now, is not only high-quality ICU care, concentrated on providing adequate respiratory support to critically ill patients, but an identification of the source and degree of mental and spiritual suffering of patients as well as their families to provide the most ethical and person-centered care during this humanitarian crisis,” they emphasized. However, they acknowledged that nonpharmacologic interventions such as mobility outside the ICU room and interactions with family members are limited by the COVID-19 situation.
The researchers noted several mechanisms by which the COVID-19 virus may cause brain damage, including through the dysfunction of the renin-angiotensin system.
“Inflammatory response of the CNS to viral infection seems to be another important reason for poor neurological outcome and occurrence of delirium,” in COVID-19 patients, they said.
As for risk-reduction strategies, the researchers noted that “delirium in mechanically ventilated patients can be reduced dramatically to 50% using a culture of lighter sedation and mobilization via the implementation of the safety bundle called the ABCDEFs promoted by the Society of Critical Care Medicine in their ICU Liberation Collaborative,” although COVID-19 isolation is a barrier, they said.
The ABCDEF bundle consists of Assessment of pain, Both spontaneous awakening trials and spontaneous breathing trials, Choice of sedation, Delirium (hyperactive or hypoactive), Early mobility, and Family presence; all of which are challenging in the COVID-19 environment, the researchers said.
They advised implementing easy screening methods for delirium to reduce the burden on medical staff, and emphasized the importance of regular patient orientation, despite social separation from family and caregivers.
“No drugs can be recommended for the prevention or treatment of ICU delirium other than avoidance of overuse of potent psychoactive agents like sedatives and neuromuscular blockers (NMB) unless patients absolutely require such management,” they added.
“Delirium is so common and so hard to manage in the COVID-19 population,” Mangala Narasimhan, DO, of Northwell Health in New Hyde Park, N.Y., said in an interview. Delirium is impacted by many sources including a viral encephalopathy, the amount and duration of sedation medications, and prolonged intubation and hypoxemia, she said. “Managing the delirium allows you to wake the patient up successfully and without a lot of discoordination. This will help with weaning,” she noted. Barriers to delirium management for COVID-19 patients include the length of time on a ventilator, as well as amount of sedatives and paralytics, and the added issues of renal insufficiency, she noted. “How they can be addressed is thoughtful plans on the addition of long-term sedation for withdrawal symptoms, and anxiolytics for the profound anxiety associated with arousal from this type of sedation on ventilators, she said. The take-home message for clinicians is the need to perform weaning trials to manage delirium in the ICU. “We have to combat this delirium in order to be successful in taking these patients off of ventilators,” she said. Dr. Narasimhan added that more research is needed on areas including drug-to-drug interactions, duration of efficacy of various drugs, and how the virus affects the brain.
“Adherence to the ABCDEF bundle can reduce the incidence of delirium, from approximately 75% of mechanically ventilated patients to 50% or less,” David L. Bowton, MD, of Wake Forest Baptist Health in Winston-Salem, N.C., said in an interview.
“Importantly, in most studies, bundle adherence reduces mortality and ICU length of stay and lowers the total cost of care. However, isolation of patients and protection of staff, visitor restrictions, and potentially stressed staffing will likely alter how most institutions approach bundle compliance,” he said. “Gathering input from infection control clinicians and bedside providers from multiple disciplines that consider these factors to critically examine current bundle procedures and workflow will be essential to the creation and/or revision of bundle processes of care that maintain the integrity of the ABCDEF bundle yet preserve staff, patient, and family safety,” he said.
“We did not have strong evidence to suggest an optimal approach to treating delirium before the advent of the COVID-19 pandemic, so I do not believe we know what the best approach is in the current environment,” Dr. Bowton added. “Further, vigilance will be necessary to ensure that altered consciousness or cognition is ICU delirium and not attributable to another cause such as drug withdrawal, drug adverse effect, or primary central nervous system infection or immune response that mandates specific therapy,” he emphasized.
For clinicians, “this study reminds us of the importance of the ABCDEF bundle to improve outcomes of critical illness,” said Dr. Bowton. “It highlights the difficulties of providing frequent reassessment of pain, comfort, reassurance, and reorientation to critically ill patients. To me, it underscores the importance of each institution critically examining staffing needs and staffing roles to mitigate these difficulties and to explore novel methods of maintaining staff-patient and family-patient interactions to enhance compliance with all elements of the ABCDEF bundle while maintaining the safety of staff and families.”
Dr. Bowton added, “When necessary, explicit modifications to existing ABCDEF bundles should be developed and disseminated to provide realistic, readily understood guidance to achieve the best possible compliance with each bundle element. One potentially underrecognized issue will be the large, hopefully temporary, number of people requiring post–critical illness rehabilitation and mental health services,” he said. “In many regions these services are already underfunded and ill-equipped to handle an increased demand for these services,” he noted.
Additional research is needed in many areas, said Dr. Bowton. “While compliance with the ABCDEF bundle decreases the incidence and duration of delirium, decreases ICU length of stay, decreases duration of mechanical ventilation, and improves mortality, many questions remain. Individual elements of the bundle have been inconsistently associated with improved outcomes,” he said. “What is the relative importance of specific elements and what are the mechanisms by which they improve outcomes?” he asked. “We still do not know how to best achieve physical/functional recovery following critical illness, which, in light of these authors’ studies relating persisting physical debility to depression (Lancet Respir Med. 2014; 2[5]:369-79), may be a key component to improving long-term outcomes,” he said.
The study received no specific funding, although several coauthors disclosed grants from agencies including the National Center for Advancing Translational Sciences, National Institute of General Medical Sciences, National Heart, Lung, and Blood Institute, and National Institute on Aging. Dr. Narasimhan and Dr. Bowton had no financial conflicts to disclose.
SOURCE: Kotfis K et al. Critical Care. 2020 Apr 28. doi: 10.1186/s13054-020-02882-x.
, and a bedside risk management strategy based on modifiable risk factors can help prevent lingering effects on cognition, according to an article published in Critical Care.
Several factors can contribute to an increased risk of ICU delirium in COVID-19 patients, wrote Katarzyna Kotfis, MD, of Pomeranian Medical University, Szczecin, Poland, and colleagues.
“In patients with COVID-19, delirium may be a manifestation of direct central nervous system invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failure, an effect of sedative strategies, prolonged mechanical ventilation time, or environmental factors, including social isolation,” they said.
Delirium in the context of COVID-19 can mean an early sign of infection, so patients should be screened using dedicated psychometric tools, the researchers wrote. Also, COVID-19 has been shown to cause pneumonia in elderly patients, who are at high risk for severe pulmonary disease related to COVID-19 and for ICU delirium generally, they said.
In addition, don’t underestimate the impact of social isolation created by quarantines, the researchers said.
“What is needed now, is not only high-quality ICU care, concentrated on providing adequate respiratory support to critically ill patients, but an identification of the source and degree of mental and spiritual suffering of patients as well as their families to provide the most ethical and person-centered care during this humanitarian crisis,” they emphasized. However, they acknowledged that nonpharmacologic interventions such as mobility outside the ICU room and interactions with family members are limited by the COVID-19 situation.
The researchers noted several mechanisms by which the COVID-19 virus may cause brain damage, including through the dysfunction of the renin-angiotensin system.
“Inflammatory response of the CNS to viral infection seems to be another important reason for poor neurological outcome and occurrence of delirium,” in COVID-19 patients, they said.
As for risk-reduction strategies, the researchers noted that “delirium in mechanically ventilated patients can be reduced dramatically to 50% using a culture of lighter sedation and mobilization via the implementation of the safety bundle called the ABCDEFs promoted by the Society of Critical Care Medicine in their ICU Liberation Collaborative,” although COVID-19 isolation is a barrier, they said.
The ABCDEF bundle consists of Assessment of pain, Both spontaneous awakening trials and spontaneous breathing trials, Choice of sedation, Delirium (hyperactive or hypoactive), Early mobility, and Family presence; all of which are challenging in the COVID-19 environment, the researchers said.
They advised implementing easy screening methods for delirium to reduce the burden on medical staff, and emphasized the importance of regular patient orientation, despite social separation from family and caregivers.
“No drugs can be recommended for the prevention or treatment of ICU delirium other than avoidance of overuse of potent psychoactive agents like sedatives and neuromuscular blockers (NMB) unless patients absolutely require such management,” they added.
“Delirium is so common and so hard to manage in the COVID-19 population,” Mangala Narasimhan, DO, of Northwell Health in New Hyde Park, N.Y., said in an interview. Delirium is impacted by many sources including a viral encephalopathy, the amount and duration of sedation medications, and prolonged intubation and hypoxemia, she said. “Managing the delirium allows you to wake the patient up successfully and without a lot of discoordination. This will help with weaning,” she noted. Barriers to delirium management for COVID-19 patients include the length of time on a ventilator, as well as amount of sedatives and paralytics, and the added issues of renal insufficiency, she noted. “How they can be addressed is thoughtful plans on the addition of long-term sedation for withdrawal symptoms, and anxiolytics for the profound anxiety associated with arousal from this type of sedation on ventilators, she said. The take-home message for clinicians is the need to perform weaning trials to manage delirium in the ICU. “We have to combat this delirium in order to be successful in taking these patients off of ventilators,” she said. Dr. Narasimhan added that more research is needed on areas including drug-to-drug interactions, duration of efficacy of various drugs, and how the virus affects the brain.
“Adherence to the ABCDEF bundle can reduce the incidence of delirium, from approximately 75% of mechanically ventilated patients to 50% or less,” David L. Bowton, MD, of Wake Forest Baptist Health in Winston-Salem, N.C., said in an interview.
“Importantly, in most studies, bundle adherence reduces mortality and ICU length of stay and lowers the total cost of care. However, isolation of patients and protection of staff, visitor restrictions, and potentially stressed staffing will likely alter how most institutions approach bundle compliance,” he said. “Gathering input from infection control clinicians and bedside providers from multiple disciplines that consider these factors to critically examine current bundle procedures and workflow will be essential to the creation and/or revision of bundle processes of care that maintain the integrity of the ABCDEF bundle yet preserve staff, patient, and family safety,” he said.
“We did not have strong evidence to suggest an optimal approach to treating delirium before the advent of the COVID-19 pandemic, so I do not believe we know what the best approach is in the current environment,” Dr. Bowton added. “Further, vigilance will be necessary to ensure that altered consciousness or cognition is ICU delirium and not attributable to another cause such as drug withdrawal, drug adverse effect, or primary central nervous system infection or immune response that mandates specific therapy,” he emphasized.
For clinicians, “this study reminds us of the importance of the ABCDEF bundle to improve outcomes of critical illness,” said Dr. Bowton. “It highlights the difficulties of providing frequent reassessment of pain, comfort, reassurance, and reorientation to critically ill patients. To me, it underscores the importance of each institution critically examining staffing needs and staffing roles to mitigate these difficulties and to explore novel methods of maintaining staff-patient and family-patient interactions to enhance compliance with all elements of the ABCDEF bundle while maintaining the safety of staff and families.”
Dr. Bowton added, “When necessary, explicit modifications to existing ABCDEF bundles should be developed and disseminated to provide realistic, readily understood guidance to achieve the best possible compliance with each bundle element. One potentially underrecognized issue will be the large, hopefully temporary, number of people requiring post–critical illness rehabilitation and mental health services,” he said. “In many regions these services are already underfunded and ill-equipped to handle an increased demand for these services,” he noted.
Additional research is needed in many areas, said Dr. Bowton. “While compliance with the ABCDEF bundle decreases the incidence and duration of delirium, decreases ICU length of stay, decreases duration of mechanical ventilation, and improves mortality, many questions remain. Individual elements of the bundle have been inconsistently associated with improved outcomes,” he said. “What is the relative importance of specific elements and what are the mechanisms by which they improve outcomes?” he asked. “We still do not know how to best achieve physical/functional recovery following critical illness, which, in light of these authors’ studies relating persisting physical debility to depression (Lancet Respir Med. 2014; 2[5]:369-79), may be a key component to improving long-term outcomes,” he said.
The study received no specific funding, although several coauthors disclosed grants from agencies including the National Center for Advancing Translational Sciences, National Institute of General Medical Sciences, National Heart, Lung, and Blood Institute, and National Institute on Aging. Dr. Narasimhan and Dr. Bowton had no financial conflicts to disclose.
SOURCE: Kotfis K et al. Critical Care. 2020 Apr 28. doi: 10.1186/s13054-020-02882-x.
FROM CRITICAL CARE
States vary in vulnerability to COVID-19 impact
West Virginia’s large elderly population and high rates of chronic kidney disease, cardiovascular disease, diabetes, and COPD make it the most vulnerable state to the coronavirus, according to a new analysis.
Vulnerability to the virus “isn’t just health related, though, as many people are harmed by the economic effects of the pandemic,” personal finance website WalletHub said May 12.
“It’s important for the U.S. to dedicate a large portion of its resources to providing medical support during the coronavirus pandemic, but we should also support people who don’t have adequate housing or enough money to survive the pandemic,” said WalletHub analyst Jill Gonzalez.
WalletHub graded each state on 28 measures – including share of obese adults, share of homes lacking access to basic hygienic facilities, and biggest increases in unemployment because of COVID-19 – grouped into three dimensions of vulnerability: medical (60% of the total score), housing (15%), and financial (25%).
Using those measures, Louisiana is the most vulnerable state after West Virginia, followed by Mississippi, Arkansas, and Alabama. All 5 states finished in the top 6 for medical vulnerability, and 4 were in the top 10 for financial vulnerability, but only 1 (Arkansas) was in the top 10 for housing vulnerability, WalletHub said.
Among the three vulnerability dimensions, West Virginia was first in medical, Hawaii (33rd overall) was first in housing, and Louisiana was first in financial. Utah is the least vulnerable state, overall, and the least vulnerable states in each dimension are, respectively, Colorado (50th overall), the District of Columbia (29th overall), and Iowa (45th overall), the report showed.
A look at the individual metrics WalletHub used shows some serious disparities:
- New Jersey’s unemployment recipiency rate of 57.2%, the highest in the country, is 6.1 times higher than North Carolina’s 9.3%.
- The highest uninsured rate, 17.4% in Texas, is 6.2 times higher than in Massachusetts, which is the lowest at 2.8%.
- In California, the share of the homeless population that is unsheltered (71.7%) is more than 33 times higher than in North Dakota (2.2%).
“The financial damage caused by COVID-19 is leaving many Americans without the means to pay their bills and purchase necessities. … The U.S. must continue to support its financially vulnerable populations even after the virus has subsided,” Ms. Gonzalez said.
West Virginia’s large elderly population and high rates of chronic kidney disease, cardiovascular disease, diabetes, and COPD make it the most vulnerable state to the coronavirus, according to a new analysis.
Vulnerability to the virus “isn’t just health related, though, as many people are harmed by the economic effects of the pandemic,” personal finance website WalletHub said May 12.
“It’s important for the U.S. to dedicate a large portion of its resources to providing medical support during the coronavirus pandemic, but we should also support people who don’t have adequate housing or enough money to survive the pandemic,” said WalletHub analyst Jill Gonzalez.
WalletHub graded each state on 28 measures – including share of obese adults, share of homes lacking access to basic hygienic facilities, and biggest increases in unemployment because of COVID-19 – grouped into three dimensions of vulnerability: medical (60% of the total score), housing (15%), and financial (25%).
Using those measures, Louisiana is the most vulnerable state after West Virginia, followed by Mississippi, Arkansas, and Alabama. All 5 states finished in the top 6 for medical vulnerability, and 4 were in the top 10 for financial vulnerability, but only 1 (Arkansas) was in the top 10 for housing vulnerability, WalletHub said.
Among the three vulnerability dimensions, West Virginia was first in medical, Hawaii (33rd overall) was first in housing, and Louisiana was first in financial. Utah is the least vulnerable state, overall, and the least vulnerable states in each dimension are, respectively, Colorado (50th overall), the District of Columbia (29th overall), and Iowa (45th overall), the report showed.
A look at the individual metrics WalletHub used shows some serious disparities:
- New Jersey’s unemployment recipiency rate of 57.2%, the highest in the country, is 6.1 times higher than North Carolina’s 9.3%.
- The highest uninsured rate, 17.4% in Texas, is 6.2 times higher than in Massachusetts, which is the lowest at 2.8%.
- In California, the share of the homeless population that is unsheltered (71.7%) is more than 33 times higher than in North Dakota (2.2%).
“The financial damage caused by COVID-19 is leaving many Americans without the means to pay their bills and purchase necessities. … The U.S. must continue to support its financially vulnerable populations even after the virus has subsided,” Ms. Gonzalez said.
West Virginia’s large elderly population and high rates of chronic kidney disease, cardiovascular disease, diabetes, and COPD make it the most vulnerable state to the coronavirus, according to a new analysis.
Vulnerability to the virus “isn’t just health related, though, as many people are harmed by the economic effects of the pandemic,” personal finance website WalletHub said May 12.
“It’s important for the U.S. to dedicate a large portion of its resources to providing medical support during the coronavirus pandemic, but we should also support people who don’t have adequate housing or enough money to survive the pandemic,” said WalletHub analyst Jill Gonzalez.
WalletHub graded each state on 28 measures – including share of obese adults, share of homes lacking access to basic hygienic facilities, and biggest increases in unemployment because of COVID-19 – grouped into three dimensions of vulnerability: medical (60% of the total score), housing (15%), and financial (25%).
Using those measures, Louisiana is the most vulnerable state after West Virginia, followed by Mississippi, Arkansas, and Alabama. All 5 states finished in the top 6 for medical vulnerability, and 4 were in the top 10 for financial vulnerability, but only 1 (Arkansas) was in the top 10 for housing vulnerability, WalletHub said.
Among the three vulnerability dimensions, West Virginia was first in medical, Hawaii (33rd overall) was first in housing, and Louisiana was first in financial. Utah is the least vulnerable state, overall, and the least vulnerable states in each dimension are, respectively, Colorado (50th overall), the District of Columbia (29th overall), and Iowa (45th overall), the report showed.
A look at the individual metrics WalletHub used shows some serious disparities:
- New Jersey’s unemployment recipiency rate of 57.2%, the highest in the country, is 6.1 times higher than North Carolina’s 9.3%.
- The highest uninsured rate, 17.4% in Texas, is 6.2 times higher than in Massachusetts, which is the lowest at 2.8%.
- In California, the share of the homeless population that is unsheltered (71.7%) is more than 33 times higher than in North Dakota (2.2%).
“The financial damage caused by COVID-19 is leaving many Americans without the means to pay their bills and purchase necessities. … The U.S. must continue to support its financially vulnerable populations even after the virus has subsided,” Ms. Gonzalez said.
Sleeve gastrectomy, antiobesity drugs underutilized
Despite an increasing rate of obesity in the United States, sleeve gastrectomy and postoperative antiobesity pharmacotherapy remain significantly underutilized, according to investigators.
A retrospective study involving almost 3 million adults with obesity found that only 0.94% had undergone sleeve gastrectomy, with 5.6% of those receiving weight-loss drugs after discharge, reported lead author Raj Shah, MD, of University Hospitals Cleveland Medical Center, and colleagues.
“While obesity has increased exponentially in the past decade, the trends of bariatric procedures and postoperative pharmacotherapy in this timeline is not well established,” the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.
According to coauthor Abbinaya Elangovan, MD, of MetroHealth Medical Center, Cleveland, existing data suggest a practice gap.
“We know from published studies that antiobesity measures – both surgical and pharmacotherapeutic – do not match the rates of obesity,” Dr. Elangovan said. “We wanted to see how many of the morbidly obese [patients] who get bariatric surgery get started on antiobesity pharmacotherapy. We selected sleeve gastrectomy, as that is the most common bariatric procedure performed in the United States in recent times.”
The investigators began by retrospectively screening 2,717,000 individuals with a body mass index (in kg/m2) of at least 40 who entered the IBM Explorys database from 2010 to 2019. Out of this group, 25,540 individuals (0.94%) had undergone sleeve gastrectomy. Annual rates of the procedure increased from 0.06% in 2010 to 0.4% in 2019 (P < .0001).
Of the 25,540 patients who underwent sleeve gastrectomy, 1,440 (5.6%) were prescribed antiobesity medication after surgery, with about half (47%) of these prescriptions written within a year. The most common medication was phentermine (66%), followed by bupropion/naltrexone (16%) and phentermine/topiramate (14.4%).
Dr. Elangovan said that the rates of surgery and antiobesity pharmacotherapy found in the study were “sparse” compared with rates of obesity.
“[Future studies need] to find the barriers to antiobesity pharmacotherapy,” Dr. Elangovan said. “We know from some of the published studies that there are differences in provider perceptions, as well as patient populations who get the therapy.”
The present analysis showed that women, African Americans, and patients with commercial insurance were significantly more likely to receive postoperative weight-loss medications than other patient subgroups.
“I think insurance could be a potential concern,” Dr. Elangovan said. “This has been shown previously in the literature.” She also suggested that women may be accessing obesity-related health care more often than men.
Discussing steps to improve interventions for patients with obesity, Dr. Elangovan emphasized the amount of data supporting antiobesity pharmacotherapy.
“We know from studies published so far that combining pharmacotherapy with behavioral modifications has a greater percentage of success, compared to behavioral modifications by themselves,” Dr. Elangovan said.
According to Dr. Elangovan, primary care providers play a key role in connecting obese patients with the treatments they need, requiring familiarity with existing guidelines.
“It helps if practicing clinicians, especially primary care providers, are familiar with bariatric surgery criteria and institution policies,” Dr. Elangovan said. “It has been shown in some studies that limited experience in prescribing and concern for adverse reactions could affect the prescription of antiobesity pharmacotherapy. Targeted interventions such as educational programs may increase the appropriate usage of medications.”
Dr. Smith disclosed a relationship with US Endoscopy.
SOURCE: Shah R et al. DDW 2020, Abstract 791.
Despite an increasing rate of obesity in the United States, sleeve gastrectomy and postoperative antiobesity pharmacotherapy remain significantly underutilized, according to investigators.
A retrospective study involving almost 3 million adults with obesity found that only 0.94% had undergone sleeve gastrectomy, with 5.6% of those receiving weight-loss drugs after discharge, reported lead author Raj Shah, MD, of University Hospitals Cleveland Medical Center, and colleagues.
“While obesity has increased exponentially in the past decade, the trends of bariatric procedures and postoperative pharmacotherapy in this timeline is not well established,” the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.
According to coauthor Abbinaya Elangovan, MD, of MetroHealth Medical Center, Cleveland, existing data suggest a practice gap.
“We know from published studies that antiobesity measures – both surgical and pharmacotherapeutic – do not match the rates of obesity,” Dr. Elangovan said. “We wanted to see how many of the morbidly obese [patients] who get bariatric surgery get started on antiobesity pharmacotherapy. We selected sleeve gastrectomy, as that is the most common bariatric procedure performed in the United States in recent times.”
The investigators began by retrospectively screening 2,717,000 individuals with a body mass index (in kg/m2) of at least 40 who entered the IBM Explorys database from 2010 to 2019. Out of this group, 25,540 individuals (0.94%) had undergone sleeve gastrectomy. Annual rates of the procedure increased from 0.06% in 2010 to 0.4% in 2019 (P < .0001).
Of the 25,540 patients who underwent sleeve gastrectomy, 1,440 (5.6%) were prescribed antiobesity medication after surgery, with about half (47%) of these prescriptions written within a year. The most common medication was phentermine (66%), followed by bupropion/naltrexone (16%) and phentermine/topiramate (14.4%).
Dr. Elangovan said that the rates of surgery and antiobesity pharmacotherapy found in the study were “sparse” compared with rates of obesity.
“[Future studies need] to find the barriers to antiobesity pharmacotherapy,” Dr. Elangovan said. “We know from some of the published studies that there are differences in provider perceptions, as well as patient populations who get the therapy.”
The present analysis showed that women, African Americans, and patients with commercial insurance were significantly more likely to receive postoperative weight-loss medications than other patient subgroups.
“I think insurance could be a potential concern,” Dr. Elangovan said. “This has been shown previously in the literature.” She also suggested that women may be accessing obesity-related health care more often than men.
Discussing steps to improve interventions for patients with obesity, Dr. Elangovan emphasized the amount of data supporting antiobesity pharmacotherapy.
“We know from studies published so far that combining pharmacotherapy with behavioral modifications has a greater percentage of success, compared to behavioral modifications by themselves,” Dr. Elangovan said.
According to Dr. Elangovan, primary care providers play a key role in connecting obese patients with the treatments they need, requiring familiarity with existing guidelines.
“It helps if practicing clinicians, especially primary care providers, are familiar with bariatric surgery criteria and institution policies,” Dr. Elangovan said. “It has been shown in some studies that limited experience in prescribing and concern for adverse reactions could affect the prescription of antiobesity pharmacotherapy. Targeted interventions such as educational programs may increase the appropriate usage of medications.”
Dr. Smith disclosed a relationship with US Endoscopy.
SOURCE: Shah R et al. DDW 2020, Abstract 791.
Despite an increasing rate of obesity in the United States, sleeve gastrectomy and postoperative antiobesity pharmacotherapy remain significantly underutilized, according to investigators.
A retrospective study involving almost 3 million adults with obesity found that only 0.94% had undergone sleeve gastrectomy, with 5.6% of those receiving weight-loss drugs after discharge, reported lead author Raj Shah, MD, of University Hospitals Cleveland Medical Center, and colleagues.
“While obesity has increased exponentially in the past decade, the trends of bariatric procedures and postoperative pharmacotherapy in this timeline is not well established,” the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.
According to coauthor Abbinaya Elangovan, MD, of MetroHealth Medical Center, Cleveland, existing data suggest a practice gap.
“We know from published studies that antiobesity measures – both surgical and pharmacotherapeutic – do not match the rates of obesity,” Dr. Elangovan said. “We wanted to see how many of the morbidly obese [patients] who get bariatric surgery get started on antiobesity pharmacotherapy. We selected sleeve gastrectomy, as that is the most common bariatric procedure performed in the United States in recent times.”
The investigators began by retrospectively screening 2,717,000 individuals with a body mass index (in kg/m2) of at least 40 who entered the IBM Explorys database from 2010 to 2019. Out of this group, 25,540 individuals (0.94%) had undergone sleeve gastrectomy. Annual rates of the procedure increased from 0.06% in 2010 to 0.4% in 2019 (P < .0001).
Of the 25,540 patients who underwent sleeve gastrectomy, 1,440 (5.6%) were prescribed antiobesity medication after surgery, with about half (47%) of these prescriptions written within a year. The most common medication was phentermine (66%), followed by bupropion/naltrexone (16%) and phentermine/topiramate (14.4%).
Dr. Elangovan said that the rates of surgery and antiobesity pharmacotherapy found in the study were “sparse” compared with rates of obesity.
“[Future studies need] to find the barriers to antiobesity pharmacotherapy,” Dr. Elangovan said. “We know from some of the published studies that there are differences in provider perceptions, as well as patient populations who get the therapy.”
The present analysis showed that women, African Americans, and patients with commercial insurance were significantly more likely to receive postoperative weight-loss medications than other patient subgroups.
“I think insurance could be a potential concern,” Dr. Elangovan said. “This has been shown previously in the literature.” She also suggested that women may be accessing obesity-related health care more often than men.
Discussing steps to improve interventions for patients with obesity, Dr. Elangovan emphasized the amount of data supporting antiobesity pharmacotherapy.
“We know from studies published so far that combining pharmacotherapy with behavioral modifications has a greater percentage of success, compared to behavioral modifications by themselves,” Dr. Elangovan said.
According to Dr. Elangovan, primary care providers play a key role in connecting obese patients with the treatments they need, requiring familiarity with existing guidelines.
“It helps if practicing clinicians, especially primary care providers, are familiar with bariatric surgery criteria and institution policies,” Dr. Elangovan said. “It has been shown in some studies that limited experience in prescribing and concern for adverse reactions could affect the prescription of antiobesity pharmacotherapy. Targeted interventions such as educational programs may increase the appropriate usage of medications.”
Dr. Smith disclosed a relationship with US Endoscopy.
SOURCE: Shah R et al. DDW 2020, Abstract 791.
FROM DDW 2020
Bronchoscopy guideline for COVID-19 pandemic: Use sparingly
With little evidence available on the role of bronchoscopy during the COVID-19 pandemic, an expert panel has published a guideline recommending its spare use in COVID-19 patients and those with suspected COVID-19 infection.
The panel stated that in the context of the COVID-19 crisis, bronchoscopy and other aerosol-generating procedures put health care workers (HCWs) at particularly high risk of exposure and infection. They recommended deferring bronchoscopy in nonurgent cases, and advised practitioners to wear personal protective equipment when performing bronchoscopy, even on asymptomatic patients.
The guideline and expert panel report have been published online in the journal Chest. CHEST and the American Association for Bronchology and Interventional Pulmonology participated in selecting the 14 panelists. “The recommendation and suggestions outlined in this document were specifically created to address what were felt to be clinically common and urgent questions that frontline clinicians are likely to face,” wrote lead author and panel cochair Momen M. Wahidi, MD, MBA, of Duke University, Durham, N.C., and colleagues.
Only one of the six recommendations is based on graded evidence; the remainder are ungraded consensus-based statements. The guideline consists of the following recommendations for performing or using bronchoscopy:
- HCWs in the procedure or recovery rooms should wear either an N-95 respirator or powered air-purifying respirator (PAPR) when performing bronchoscopy on patients suspected or confirmed to have COVID-19. They should wear personal protective equipment (PPE) that includes a face shield, gown, and gloves, and they should discard N-95 respirators after performing bronchoscopy.
- A nasopharyngeal specimen in COVID-19 suspects should be obtained before performing bronchoscopy. If the patient has severe or progressive disease that requires intubation but an additional specimen is needed to confirm COVID-19 or another diagnosis that could change the treatment course, an option would be lower-respiratory specimen from the endotracheal aspirate or bronchoscopy with bronchoalveolar lavage.
- HCWs should wear an N-95 or PAPR when doing bronchoscopy on asymptomatic patients in an area with community spread of COVID-19 – again, with the PPE designated in the first recommendation.
- Test for COVID-19 before doing bronchoscopy on asymptomatic patients. Defer nonurgent bronchoscopy if the test is positive. If it’s negative, follow the recommendations regarding respirators and PPE when doing bronchoscopy.
- Perform timely bronchoscopy when indicated even in an area with known community spread of COVID-19. This is the only graded recommendation among the six (Grade 2C) and may be the most nuanced. Local teams should develop strategies for using bronchoscopy in their setting, taking into account local resources and availability of PPE, and they should send noninfected cancer patients from resource-depleted hospitals to other centers.
- Base the timing of bronchoscopy in patients recovering after COVID-19 on the indication for the procedure, disease severity, and time duration since symptoms resolved. The recommendation noted that the exact timing is still unknown, but that a wait of at least 30 days after symptoms recede is “reasonable.”
The expert panel added a noteworthy caveat to the recommendations. “We would like to stress that these protective strategies can be rendered completely ineffective if proper training on donning and doffing is not provided to HCW,” Dr. Wahidi and colleagues wrote. “Proper personnel instruction and practice for wearing PPE should receive as much attention by health facilities as the chosen strategy for protection.”
Dr. Wahidi and colleagues have no financial relationships to disclose.
SOURCE: Wahidi MM et al. CHEST. 2020 Apr 30. doi: 10.1016/j.chest.2020.04.036.
With little evidence available on the role of bronchoscopy during the COVID-19 pandemic, an expert panel has published a guideline recommending its spare use in COVID-19 patients and those with suspected COVID-19 infection.
The panel stated that in the context of the COVID-19 crisis, bronchoscopy and other aerosol-generating procedures put health care workers (HCWs) at particularly high risk of exposure and infection. They recommended deferring bronchoscopy in nonurgent cases, and advised practitioners to wear personal protective equipment when performing bronchoscopy, even on asymptomatic patients.
The guideline and expert panel report have been published online in the journal Chest. CHEST and the American Association for Bronchology and Interventional Pulmonology participated in selecting the 14 panelists. “The recommendation and suggestions outlined in this document were specifically created to address what were felt to be clinically common and urgent questions that frontline clinicians are likely to face,” wrote lead author and panel cochair Momen M. Wahidi, MD, MBA, of Duke University, Durham, N.C., and colleagues.
Only one of the six recommendations is based on graded evidence; the remainder are ungraded consensus-based statements. The guideline consists of the following recommendations for performing or using bronchoscopy:
- HCWs in the procedure or recovery rooms should wear either an N-95 respirator or powered air-purifying respirator (PAPR) when performing bronchoscopy on patients suspected or confirmed to have COVID-19. They should wear personal protective equipment (PPE) that includes a face shield, gown, and gloves, and they should discard N-95 respirators after performing bronchoscopy.
- A nasopharyngeal specimen in COVID-19 suspects should be obtained before performing bronchoscopy. If the patient has severe or progressive disease that requires intubation but an additional specimen is needed to confirm COVID-19 or another diagnosis that could change the treatment course, an option would be lower-respiratory specimen from the endotracheal aspirate or bronchoscopy with bronchoalveolar lavage.
- HCWs should wear an N-95 or PAPR when doing bronchoscopy on asymptomatic patients in an area with community spread of COVID-19 – again, with the PPE designated in the first recommendation.
- Test for COVID-19 before doing bronchoscopy on asymptomatic patients. Defer nonurgent bronchoscopy if the test is positive. If it’s negative, follow the recommendations regarding respirators and PPE when doing bronchoscopy.
- Perform timely bronchoscopy when indicated even in an area with known community spread of COVID-19. This is the only graded recommendation among the six (Grade 2C) and may be the most nuanced. Local teams should develop strategies for using bronchoscopy in their setting, taking into account local resources and availability of PPE, and they should send noninfected cancer patients from resource-depleted hospitals to other centers.
- Base the timing of bronchoscopy in patients recovering after COVID-19 on the indication for the procedure, disease severity, and time duration since symptoms resolved. The recommendation noted that the exact timing is still unknown, but that a wait of at least 30 days after symptoms recede is “reasonable.”
The expert panel added a noteworthy caveat to the recommendations. “We would like to stress that these protective strategies can be rendered completely ineffective if proper training on donning and doffing is not provided to HCW,” Dr. Wahidi and colleagues wrote. “Proper personnel instruction and practice for wearing PPE should receive as much attention by health facilities as the chosen strategy for protection.”
Dr. Wahidi and colleagues have no financial relationships to disclose.
SOURCE: Wahidi MM et al. CHEST. 2020 Apr 30. doi: 10.1016/j.chest.2020.04.036.
With little evidence available on the role of bronchoscopy during the COVID-19 pandemic, an expert panel has published a guideline recommending its spare use in COVID-19 patients and those with suspected COVID-19 infection.
The panel stated that in the context of the COVID-19 crisis, bronchoscopy and other aerosol-generating procedures put health care workers (HCWs) at particularly high risk of exposure and infection. They recommended deferring bronchoscopy in nonurgent cases, and advised practitioners to wear personal protective equipment when performing bronchoscopy, even on asymptomatic patients.
The guideline and expert panel report have been published online in the journal Chest. CHEST and the American Association for Bronchology and Interventional Pulmonology participated in selecting the 14 panelists. “The recommendation and suggestions outlined in this document were specifically created to address what were felt to be clinically common and urgent questions that frontline clinicians are likely to face,” wrote lead author and panel cochair Momen M. Wahidi, MD, MBA, of Duke University, Durham, N.C., and colleagues.
Only one of the six recommendations is based on graded evidence; the remainder are ungraded consensus-based statements. The guideline consists of the following recommendations for performing or using bronchoscopy:
- HCWs in the procedure or recovery rooms should wear either an N-95 respirator or powered air-purifying respirator (PAPR) when performing bronchoscopy on patients suspected or confirmed to have COVID-19. They should wear personal protective equipment (PPE) that includes a face shield, gown, and gloves, and they should discard N-95 respirators after performing bronchoscopy.
- A nasopharyngeal specimen in COVID-19 suspects should be obtained before performing bronchoscopy. If the patient has severe or progressive disease that requires intubation but an additional specimen is needed to confirm COVID-19 or another diagnosis that could change the treatment course, an option would be lower-respiratory specimen from the endotracheal aspirate or bronchoscopy with bronchoalveolar lavage.
- HCWs should wear an N-95 or PAPR when doing bronchoscopy on asymptomatic patients in an area with community spread of COVID-19 – again, with the PPE designated in the first recommendation.
- Test for COVID-19 before doing bronchoscopy on asymptomatic patients. Defer nonurgent bronchoscopy if the test is positive. If it’s negative, follow the recommendations regarding respirators and PPE when doing bronchoscopy.
- Perform timely bronchoscopy when indicated even in an area with known community spread of COVID-19. This is the only graded recommendation among the six (Grade 2C) and may be the most nuanced. Local teams should develop strategies for using bronchoscopy in their setting, taking into account local resources and availability of PPE, and they should send noninfected cancer patients from resource-depleted hospitals to other centers.
- Base the timing of bronchoscopy in patients recovering after COVID-19 on the indication for the procedure, disease severity, and time duration since symptoms resolved. The recommendation noted that the exact timing is still unknown, but that a wait of at least 30 days after symptoms recede is “reasonable.”
The expert panel added a noteworthy caveat to the recommendations. “We would like to stress that these protective strategies can be rendered completely ineffective if proper training on donning and doffing is not provided to HCW,” Dr. Wahidi and colleagues wrote. “Proper personnel instruction and practice for wearing PPE should receive as much attention by health facilities as the chosen strategy for protection.”
Dr. Wahidi and colleagues have no financial relationships to disclose.
SOURCE: Wahidi MM et al. CHEST. 2020 Apr 30. doi: 10.1016/j.chest.2020.04.036.
FROM CHEST
Many hydroxychloroquine COVID-19 prophylaxis trials lack ECG screening
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
REPORTING FROM JACC
Obesity can shift severe COVID-19 to younger age groups
published in The Lancet.
“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.
“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.
The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.
But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.
The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”
“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m2,” he added. “The relationship was pretty tight, pretty quick.”
“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.
Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.
“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.
“We should think of them as a susceptible population.”
Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.
“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
Trio of mechanisms explain obesity’s extra COVID-19 risks
Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.
When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.
Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.
The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.
Median BMI among study participants was 29.3 kg/m2, with only a quarter having a BMI lower than 26 kg/m2 and another 25% having a BMI higher than 34.7 kg/m2.
Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”
He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.
For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.
“Morbid obesity itself is sort of proinflammatory,” he continued.
“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”
Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.
“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
Sensitivity needed in public messaging about risks, but test sooner
With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.
Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”
Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”
But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.
And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.
“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.
Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.
Kass and Heymsfield have declared no relevant financial relationships.
This article first appeared on Medscape.com.
published in The Lancet.
“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.
“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.
The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.
But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.
The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”
“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m2,” he added. “The relationship was pretty tight, pretty quick.”
“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.
Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.
“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.
“We should think of them as a susceptible population.”
Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.
“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
Trio of mechanisms explain obesity’s extra COVID-19 risks
Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.
When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.
Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.
The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.
Median BMI among study participants was 29.3 kg/m2, with only a quarter having a BMI lower than 26 kg/m2 and another 25% having a BMI higher than 34.7 kg/m2.
Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”
He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.
For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.
“Morbid obesity itself is sort of proinflammatory,” he continued.
“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”
Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.
“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
Sensitivity needed in public messaging about risks, but test sooner
With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.
Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”
Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”
But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.
And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.
“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.
Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.
Kass and Heymsfield have declared no relevant financial relationships.
This article first appeared on Medscape.com.
published in The Lancet.
“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.
“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.
The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.
But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.
The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”
“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m2,” he added. “The relationship was pretty tight, pretty quick.”
“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.
Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.
“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.
“We should think of them as a susceptible population.”
Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.
“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
Trio of mechanisms explain obesity’s extra COVID-19 risks
Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.
When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.
Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.
The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.
Median BMI among study participants was 29.3 kg/m2, with only a quarter having a BMI lower than 26 kg/m2 and another 25% having a BMI higher than 34.7 kg/m2.
Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”
He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.
For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.
“Morbid obesity itself is sort of proinflammatory,” he continued.
“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”
Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.
“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
Sensitivity needed in public messaging about risks, but test sooner
With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.
Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”
Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”
But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.
And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.
“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.
Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.
Kass and Heymsfield have declared no relevant financial relationships.
This article first appeared on Medscape.com.
Triple-antiviral combo speeds COVID-19 recovery
A triple-antiviral therapy regimen of interferon-beta1, lopinavir/ritonavir, and ribavirin shortened median time to COVID-19 viral negativity by 5 days in a small trial from Hong Kong.
In an open-label, randomized phase 2 trial in patients with mild or moderate COVID-19 infections, the median time to viral negativity by nasopharyngeal swab was 7 days for 86 patients assigned to receive a 14-day course of lopinavir 400 mg and ritonavir 100 mg every 12 hours, ribavirin 400 mg every 12 hours, and three doses of 8 million international units of interferon beta-1b on alternate days, compared with a median time to negativity of 12 days for patients treated with lopinavir/ritonavir alone (P = .0010), wrote Ivan Fan-Ngai Hung, MD, from Gleaneagles Hospital in Hong Kong, and colleagues.
“Triple-antiviral therapy with interferon beta-1b, lopinavir/ritonavir, and ribavirin were safe and superior to lopinavir/ritonavir alone in shortening virus shedding, alleviating symptoms, and facilitating discharge of patients with mild to moderate COVID-19,” they wrote in a study published online in The Lancet.
Patients who received the combination also had significantly shorter time to complete alleviation of symptoms as assessed by a National Early Warning Score 2 (NEWS2, a system for detecting clinical deterioration in patients with acute illnesses) score of 0 (4 vs. 8 days, respectively; hazard ratio 3.92, P < .0001), and to a Sequential Organ Failure Assessment (SOFA) score of 0 (3 vs. 8 days, HR 1.89, P = .041).
The median hospital stay was 9 days for patients treated with the combination, compared with 14.5 days for controls (HR 2.72, P = .016).
In most patients treated with the combination, SARS-CoV-2 viral load was effectively suppressed in all clinical specimens, including nasopharyngeal swabs, throat and posterior oropharyngeal saliva, and stool.
In addition, serum levels of interleukin 6 (IL-6) – an inflammatory cytokine implicated in the cytokine storm frequently seen in patients with severe COVID-19 infections – were significantly lower on treatment days 2, 6, and 8 in patients treated with the combination, compared with those treated with lopinavir/ritonavir alone.
“Our trial demonstrates that early treatment of mild to moderate COVID-19 with a triple combination of antiviral drugs may rapidly suppress the amount of virus in a patient’s body, relieve symptoms, and reduce the risk to health care workers by reducing the duration and quantity of viral shedding (when the virus is detectable and potentially transmissible). Furthermore, the treatment combination appeared safe and well tolerated by patients,” said lead investigator Professor Kwok-Yung Yuen from the University of Hong Kong, in a statement.
“Despite these encouraging findings,” he continued, “we must confirm in larger phase 3 trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness (in whom the virus has had more time to replicate).”
Plausible rationale
Benjamin Medoff, MD, chief of the division of pulmonary and critical care medicine at Massachusetts General Hospital in Boston, who was not involved in the study, said in an interview that the biologic rationale for the combination is plausible.
“I think this is a promising study that suggests that a regimen of interferon beta-1b, lopinavir/ritonavir, and ribavirin can shorten the duration of infection and improve symptoms in COVID-19 patients especially if started early in disease, in less than 7 days of symptom onset,” he said in reply to a request for expert analysis.
“The open-label nature and small size of the study limits the broad use of the regimen as noted by the authors, and it’s important to emphasize that the subjects enrolled did not have very severe disease (not in the ICU). However, the study does suggest that a larger truly randomized study is warranted,” he said.
AIDS drugs repurposed
Lopinavir/ritonavir is commonly used to treat HIV/AIDS throughout the world, and the investigators had previously reported that the antiviral agents combined with ribavirin reduced deaths and the need for intensive ventilator support among patients with SARS-CoV, the betacoronavirus that causes severe acute respiratory syndrome (SARS), and antivirals have shown in vitro activity against both SARS-CoV and MERS-CoV, the closely related pathogen that causes Middle East respiratory syndrome.
“ However the viral load of SARS and MERS peaks at around day 7-10 after symptom onset, whereas the viral load of COVID-19 peaks at the time of presentation, similar to influenza. Experience from the treatment of patients with influenza who are admitted to hospital suggested that a combination of multiple antiviral drugs is more effective than single-drug treatments in this setting of patients with a high viral load at presentation,” the investigators wrote.
To test this, they enrolled adults patients admitted to one of six Hong Kong Hospitals for virologically confirmed COVID-19 infections from Feb. 10 through March 20, 2020.
A total of 86 patients were randomly assigned to the combination and 41 to lopinavir/ritonavir alone as controls, at doses described above.
Patients who entered the trial within less than 7 days of symptom onset received the triple combination, with interferon dosing adjusted according to the day that treatment started. Patients recruited 1 or 2 days after symptom onset received three doses of interferon, patients started on day 3 or 4 received two doses, and those started on days 5 or 6 received one interferon dose. Patients recruited 7 days or later from symptom onset did not receive interferon beta-1b because of its proinflammatory effects.
In post-hoc analysis by day of treatment initiation, clinical and virological outcomes (except stool samples) were superior in patients admitted less than 7 days after symptom onset for the 52 patients who received a least one interferon dose plus lopinavir/ritonavir and ribavirin, compared with 24 patients randomized to the control arm (lopinavir/ritonavir only). In contrast, among patients admitted and started on treatment at day 7 or later after symptom onset, there were no differences between those who received lopinavir/ritonavir alone or combined with ribavirin.
Adverse events were reported in 41 of 86 patients in the combination group and 20 of 41 patients in the control arm. The most common adverse events were diarrhea, occurring in 52 of all 127 patients, fever in 48, nausea in 43, and elevated alanine transaminase level in 18. The side effects generally resolved within 3 days of the start of treatments.
There were no serious adverse events reported in the combination group. One patient in the control group had impaired hepatic enzymes requiring discontinuation of treatment. No patients died during the study.
The study was funded by the Shaw Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine. The authors and Dr. Medoff declared no competing interests.
SOURCE: Hung IFN et al. Lancet. 2020 May 8. doi: 10.1016/S0140-6736(20)31101-6.
A triple-antiviral therapy regimen of interferon-beta1, lopinavir/ritonavir, and ribavirin shortened median time to COVID-19 viral negativity by 5 days in a small trial from Hong Kong.
In an open-label, randomized phase 2 trial in patients with mild or moderate COVID-19 infections, the median time to viral negativity by nasopharyngeal swab was 7 days for 86 patients assigned to receive a 14-day course of lopinavir 400 mg and ritonavir 100 mg every 12 hours, ribavirin 400 mg every 12 hours, and three doses of 8 million international units of interferon beta-1b on alternate days, compared with a median time to negativity of 12 days for patients treated with lopinavir/ritonavir alone (P = .0010), wrote Ivan Fan-Ngai Hung, MD, from Gleaneagles Hospital in Hong Kong, and colleagues.
“Triple-antiviral therapy with interferon beta-1b, lopinavir/ritonavir, and ribavirin were safe and superior to lopinavir/ritonavir alone in shortening virus shedding, alleviating symptoms, and facilitating discharge of patients with mild to moderate COVID-19,” they wrote in a study published online in The Lancet.
Patients who received the combination also had significantly shorter time to complete alleviation of symptoms as assessed by a National Early Warning Score 2 (NEWS2, a system for detecting clinical deterioration in patients with acute illnesses) score of 0 (4 vs. 8 days, respectively; hazard ratio 3.92, P < .0001), and to a Sequential Organ Failure Assessment (SOFA) score of 0 (3 vs. 8 days, HR 1.89, P = .041).
The median hospital stay was 9 days for patients treated with the combination, compared with 14.5 days for controls (HR 2.72, P = .016).
In most patients treated with the combination, SARS-CoV-2 viral load was effectively suppressed in all clinical specimens, including nasopharyngeal swabs, throat and posterior oropharyngeal saliva, and stool.
In addition, serum levels of interleukin 6 (IL-6) – an inflammatory cytokine implicated in the cytokine storm frequently seen in patients with severe COVID-19 infections – were significantly lower on treatment days 2, 6, and 8 in patients treated with the combination, compared with those treated with lopinavir/ritonavir alone.
“Our trial demonstrates that early treatment of mild to moderate COVID-19 with a triple combination of antiviral drugs may rapidly suppress the amount of virus in a patient’s body, relieve symptoms, and reduce the risk to health care workers by reducing the duration and quantity of viral shedding (when the virus is detectable and potentially transmissible). Furthermore, the treatment combination appeared safe and well tolerated by patients,” said lead investigator Professor Kwok-Yung Yuen from the University of Hong Kong, in a statement.
“Despite these encouraging findings,” he continued, “we must confirm in larger phase 3 trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness (in whom the virus has had more time to replicate).”
Plausible rationale
Benjamin Medoff, MD, chief of the division of pulmonary and critical care medicine at Massachusetts General Hospital in Boston, who was not involved in the study, said in an interview that the biologic rationale for the combination is plausible.
“I think this is a promising study that suggests that a regimen of interferon beta-1b, lopinavir/ritonavir, and ribavirin can shorten the duration of infection and improve symptoms in COVID-19 patients especially if started early in disease, in less than 7 days of symptom onset,” he said in reply to a request for expert analysis.
“The open-label nature and small size of the study limits the broad use of the regimen as noted by the authors, and it’s important to emphasize that the subjects enrolled did not have very severe disease (not in the ICU). However, the study does suggest that a larger truly randomized study is warranted,” he said.
AIDS drugs repurposed
Lopinavir/ritonavir is commonly used to treat HIV/AIDS throughout the world, and the investigators had previously reported that the antiviral agents combined with ribavirin reduced deaths and the need for intensive ventilator support among patients with SARS-CoV, the betacoronavirus that causes severe acute respiratory syndrome (SARS), and antivirals have shown in vitro activity against both SARS-CoV and MERS-CoV, the closely related pathogen that causes Middle East respiratory syndrome.
“ However the viral load of SARS and MERS peaks at around day 7-10 after symptom onset, whereas the viral load of COVID-19 peaks at the time of presentation, similar to influenza. Experience from the treatment of patients with influenza who are admitted to hospital suggested that a combination of multiple antiviral drugs is more effective than single-drug treatments in this setting of patients with a high viral load at presentation,” the investigators wrote.
To test this, they enrolled adults patients admitted to one of six Hong Kong Hospitals for virologically confirmed COVID-19 infections from Feb. 10 through March 20, 2020.
A total of 86 patients were randomly assigned to the combination and 41 to lopinavir/ritonavir alone as controls, at doses described above.
Patients who entered the trial within less than 7 days of symptom onset received the triple combination, with interferon dosing adjusted according to the day that treatment started. Patients recruited 1 or 2 days after symptom onset received three doses of interferon, patients started on day 3 or 4 received two doses, and those started on days 5 or 6 received one interferon dose. Patients recruited 7 days or later from symptom onset did not receive interferon beta-1b because of its proinflammatory effects.
In post-hoc analysis by day of treatment initiation, clinical and virological outcomes (except stool samples) were superior in patients admitted less than 7 days after symptom onset for the 52 patients who received a least one interferon dose plus lopinavir/ritonavir and ribavirin, compared with 24 patients randomized to the control arm (lopinavir/ritonavir only). In contrast, among patients admitted and started on treatment at day 7 or later after symptom onset, there were no differences between those who received lopinavir/ritonavir alone or combined with ribavirin.
Adverse events were reported in 41 of 86 patients in the combination group and 20 of 41 patients in the control arm. The most common adverse events were diarrhea, occurring in 52 of all 127 patients, fever in 48, nausea in 43, and elevated alanine transaminase level in 18. The side effects generally resolved within 3 days of the start of treatments.
There were no serious adverse events reported in the combination group. One patient in the control group had impaired hepatic enzymes requiring discontinuation of treatment. No patients died during the study.
The study was funded by the Shaw Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine. The authors and Dr. Medoff declared no competing interests.
SOURCE: Hung IFN et al. Lancet. 2020 May 8. doi: 10.1016/S0140-6736(20)31101-6.
A triple-antiviral therapy regimen of interferon-beta1, lopinavir/ritonavir, and ribavirin shortened median time to COVID-19 viral negativity by 5 days in a small trial from Hong Kong.
In an open-label, randomized phase 2 trial in patients with mild or moderate COVID-19 infections, the median time to viral negativity by nasopharyngeal swab was 7 days for 86 patients assigned to receive a 14-day course of lopinavir 400 mg and ritonavir 100 mg every 12 hours, ribavirin 400 mg every 12 hours, and three doses of 8 million international units of interferon beta-1b on alternate days, compared with a median time to negativity of 12 days for patients treated with lopinavir/ritonavir alone (P = .0010), wrote Ivan Fan-Ngai Hung, MD, from Gleaneagles Hospital in Hong Kong, and colleagues.
“Triple-antiviral therapy with interferon beta-1b, lopinavir/ritonavir, and ribavirin were safe and superior to lopinavir/ritonavir alone in shortening virus shedding, alleviating symptoms, and facilitating discharge of patients with mild to moderate COVID-19,” they wrote in a study published online in The Lancet.
Patients who received the combination also had significantly shorter time to complete alleviation of symptoms as assessed by a National Early Warning Score 2 (NEWS2, a system for detecting clinical deterioration in patients with acute illnesses) score of 0 (4 vs. 8 days, respectively; hazard ratio 3.92, P < .0001), and to a Sequential Organ Failure Assessment (SOFA) score of 0 (3 vs. 8 days, HR 1.89, P = .041).
The median hospital stay was 9 days for patients treated with the combination, compared with 14.5 days for controls (HR 2.72, P = .016).
In most patients treated with the combination, SARS-CoV-2 viral load was effectively suppressed in all clinical specimens, including nasopharyngeal swabs, throat and posterior oropharyngeal saliva, and stool.
In addition, serum levels of interleukin 6 (IL-6) – an inflammatory cytokine implicated in the cytokine storm frequently seen in patients with severe COVID-19 infections – were significantly lower on treatment days 2, 6, and 8 in patients treated with the combination, compared with those treated with lopinavir/ritonavir alone.
“Our trial demonstrates that early treatment of mild to moderate COVID-19 with a triple combination of antiviral drugs may rapidly suppress the amount of virus in a patient’s body, relieve symptoms, and reduce the risk to health care workers by reducing the duration and quantity of viral shedding (when the virus is detectable and potentially transmissible). Furthermore, the treatment combination appeared safe and well tolerated by patients,” said lead investigator Professor Kwok-Yung Yuen from the University of Hong Kong, in a statement.
“Despite these encouraging findings,” he continued, “we must confirm in larger phase 3 trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness (in whom the virus has had more time to replicate).”
Plausible rationale
Benjamin Medoff, MD, chief of the division of pulmonary and critical care medicine at Massachusetts General Hospital in Boston, who was not involved in the study, said in an interview that the biologic rationale for the combination is plausible.
“I think this is a promising study that suggests that a regimen of interferon beta-1b, lopinavir/ritonavir, and ribavirin can shorten the duration of infection and improve symptoms in COVID-19 patients especially if started early in disease, in less than 7 days of symptom onset,” he said in reply to a request for expert analysis.
“The open-label nature and small size of the study limits the broad use of the regimen as noted by the authors, and it’s important to emphasize that the subjects enrolled did not have very severe disease (not in the ICU). However, the study does suggest that a larger truly randomized study is warranted,” he said.
AIDS drugs repurposed
Lopinavir/ritonavir is commonly used to treat HIV/AIDS throughout the world, and the investigators had previously reported that the antiviral agents combined with ribavirin reduced deaths and the need for intensive ventilator support among patients with SARS-CoV, the betacoronavirus that causes severe acute respiratory syndrome (SARS), and antivirals have shown in vitro activity against both SARS-CoV and MERS-CoV, the closely related pathogen that causes Middle East respiratory syndrome.
“ However the viral load of SARS and MERS peaks at around day 7-10 after symptom onset, whereas the viral load of COVID-19 peaks at the time of presentation, similar to influenza. Experience from the treatment of patients with influenza who are admitted to hospital suggested that a combination of multiple antiviral drugs is more effective than single-drug treatments in this setting of patients with a high viral load at presentation,” the investigators wrote.
To test this, they enrolled adults patients admitted to one of six Hong Kong Hospitals for virologically confirmed COVID-19 infections from Feb. 10 through March 20, 2020.
A total of 86 patients were randomly assigned to the combination and 41 to lopinavir/ritonavir alone as controls, at doses described above.
Patients who entered the trial within less than 7 days of symptom onset received the triple combination, with interferon dosing adjusted according to the day that treatment started. Patients recruited 1 or 2 days after symptom onset received three doses of interferon, patients started on day 3 or 4 received two doses, and those started on days 5 or 6 received one interferon dose. Patients recruited 7 days or later from symptom onset did not receive interferon beta-1b because of its proinflammatory effects.
In post-hoc analysis by day of treatment initiation, clinical and virological outcomes (except stool samples) were superior in patients admitted less than 7 days after symptom onset for the 52 patients who received a least one interferon dose plus lopinavir/ritonavir and ribavirin, compared with 24 patients randomized to the control arm (lopinavir/ritonavir only). In contrast, among patients admitted and started on treatment at day 7 or later after symptom onset, there were no differences between those who received lopinavir/ritonavir alone or combined with ribavirin.
Adverse events were reported in 41 of 86 patients in the combination group and 20 of 41 patients in the control arm. The most common adverse events were diarrhea, occurring in 52 of all 127 patients, fever in 48, nausea in 43, and elevated alanine transaminase level in 18. The side effects generally resolved within 3 days of the start of treatments.
There were no serious adverse events reported in the combination group. One patient in the control group had impaired hepatic enzymes requiring discontinuation of treatment. No patients died during the study.
The study was funded by the Shaw Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine. The authors and Dr. Medoff declared no competing interests.
SOURCE: Hung IFN et al. Lancet. 2020 May 8. doi: 10.1016/S0140-6736(20)31101-6.
FROM THE LANCET
Bacteroides Fragilis Vertebral Osteomyelitis and Discitis: “Back” to Susceptibility Testing
Acute pyogenic vertebral osteomyelitis is often due to hematogenous spread of aerobic bacteria.1-4 Conversely, only 0.5% of anaerobic bacteremias lead to osteomyelitis.5 Anaerobic osteomyelitis typically results from the contiguous spread of polymicrobial infections through breaks in the gut mucosal barrier and involves the vertebral bodies in only 2% to 5% of cases.5,6 Although Bacteroides fragilis (B fragilis) is the most common anaerobic pathogen cultivated from blood, accounting for about half of all anaerobic blood isolates, it seldom leads to osteomyelitis.1,2,7-11 We report an uncommon case of B fragilis bacteremia and vertebral osteomyelitis confounded by uncertainties in anaerobic identification and susceptibilities.
Case Presentation
A healthy-appearing male aged 55 years presented to the Naval Medical Center Portsmouth (NMCP) with subacute low back pain and fevers of 103 °F for > 3 weeks. While traveling 4 weeks prior, he completed a course of oseltamivir for influenza B infection; afterward, he was diagnosed with community-acquired pneumonia and treated with a dose of ceftriaxone and a 7-day course of doxycycline. The patient presented to the same facility a week later for low back pain and nonresolving respiratory symptoms, and his therapy was changed to azithromycin, cefuroxime, prednisone, and inhalers. Additionally, after being treated for influenza, he developed constipation and hematochezia for which he did not seek care. The hematochezia was similar to a previous episode from an anal fissure 1 year prior that resolved with stool softeners. When he was finally seen at NMCP after 3 weeks of worsening back pain and fevers, lumbosacral magnetic resonance imaging (MRI) demonstrated vertebral osteomyelitis and discitis at L4-L5 and admitted to the hospital (Figure 1).
After a fluoroscopy-guided biopsy of the L4 vertebral body on hospital day 1, the patient was started on cefepime and vancomycin. The biopsy sample was inoculated onto solid media (blood agar, chocolate agar, and MacConkey agar) and incubated at 36 °C for 24 hours in a 5% CO2 atmosphere, as well as onto Shaedler agar with vitamin K and chopped meat glucose broth and incubated at 36 °C for 48 hours under anaerobic conditions. Metronidazole was added and vancomycin discontinued after 2 anaerobic blood culture vials obtained on hospital day 1, incubated in a Becton Dickinson BACTEC FX automated system, which demonstrated Gram-negative bacilli after 48 hours. The blood culture isolates demonstrated a > 99% probability of being identified as ß-lactamase positive Prevotella loescheii using Thermo Fischer Scientific RapID ANA II biochemical testing. Nitrocefinase discs were used to detect ß-lactamase activity.
The biopsy demonstrated nongranulomatous focal areas of necrotic bone and neutrophilia in a hematopoietic background consistent with acute osteomyelitis (Figure 2); on hospital day 4, ß-lactamase positive B fragilis grew from the bone culture. Additionally, 1 anaerobic vial from a surveillance blood culture set that was obtained on hospital day 3 grew ß-lactamasepositive B fragilis using the same identification methods. With these results he was thought to have a polymicrobial infection (B fragilis and Prevotella loescheii [P loescheii]) from a suspected bowel source based on his hematochezia and history of anal fissure. No aerobic, Gram-negative enterobacteriaceae were isolated, but he had previously been on cefuroxime, which has potential activity against these organisms, for ≥ 2 weeks prior to hospitalization and cultures. He was discharged on moxifloxacin and metronidazole pending final culture results, including requested anaerobic susceptibility testing.
At 1-week follow-up, both aerobic and anaerobic vials from surveillance blood cultures remained negative for any microbes, so antibiotics were deescalated to moxifloxacin monotherapy. However, after 3 days the patient was readmitted for increasing C-reactive protein (CRP) levels and intractable back pain with worsening bilateral radiculopathy. A repeat MRI demonstrated interval disease progression with near obliteration of the L4-L5 disc space and hyperenhancement of the prevertebral soft tissues and adjacent psoas musculature without focal rim-enhancing fluid collection (Figure 3). After repeat L4 biopsy, metronidazole was restarted and ertapenem added for enterobacteriaceae coverage, given the known B fragilis and potential suppression from previous cephalosporin therapy; moxifloxacin was discontinued. L4 biopsy cultures showed no growth, and CRP levels trended down from 154.2 mg/L (start of first admission) to 42.4 mg/L (start of second admission) to 14.9 mg/L (day of discharge) (reference range, 5-9.9 mg/L). He was discharged on ertapenem and metronidazole. He completed a 6-week course without further complication.
During antibiotic therapy he had an unremarkable colonoscopy, CRP normalized to 2.6 mg/L (reference range, 0-4.9 mg/L), and he underwent successful L4-L5 transforaminal lumbar interbody fusion 2 weeks after finishing antibiotics.
We retroactively sent both P loescheii isolates and the 1 B fragilis isolate that grew from the surveillance blood culture to the Multidrug-resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Army Institute of Research for identification confirmation and susceptibility analysis. Whole genome sequencing with single nucleotide polymorphism (SNP)-based analysis revealed all isolates were 100% identical and consistent with B fragilis and not P loescheii, based on clustering around other B fragilis sequences found in the National Center for Biotechnology Information (NCBI) Genbank database (Figure 4). All isolates carried the antibiotic resistance genes— cepA, sul(2), tetQ— encoding for possible resistance to cephalosporins, sulphonamides, and tetracyclines, respectively; as well as a point mutation in the gyrA gene (Ser82Phe). None of the isolates carried the nim gene, and screening for the 3 subtypes of B fragilis enterotoxin gene (bft-1, bft-2, bft-3) was negative. Eventual susceptibility testing at the Mayo Clinic several months after the conclusion of the case indicated that the B fragilis isolate was sensitive to piperacillin-tazobactam, ertapenem, clindamycin, and metronidazole; however, testing was not performed against moxifloxacin.
Discussion
In the era of growing antibiotic resistance patterns, antimicrobial stewardship programs recommend interventions to improve antimicrobial use through targeted narrow- spectrum antibiotics.12 The Clinical and Laboratory Standards Institute (CLSI) maintains guidelines on the major indications for anaerobic antimicrobial susceptibility testing (AST) to help direct narrow-targeted antimicrobial therapy. However, in a 2008 practice survey Goldstein and colleagues reported that less than half of US hospitals performed anaerobic AST, and only 21% of these facilities did it in-house, while the remainder sent out their isolates for testing.11-14 The CLSI major indications for AST include situations in which the selection of agents is important because of the (1) known resistance of a particular species; (2) confirmation of appropriate therapy for severe infections or for those that may require long-term therapy; (3) persistence of infection despite adequate treatment with an appropriate therapeutic regimen; and (4) difficulty in making empirical decisions based on precedent.14 Additionally, isolates from brain abscess, endocarditis, osteomyelitis, joint infection, infection of prosthetic devices or vascular grafts, bacteremia, and normally sterile body sites (unless contamination suspected) should be tested.14
Because of the lack of anaerobic AST, health care providers must base empiric treatment on reported sensitivities from the medical literature. Empiric selection of antimicrobials for anaerobic infections is made even more challenging by the increased rates of resistance reported in the literature, leading to recommendations to increase susceptibility testing to guide therapy.13,15,16 Empiric therapy of deep-seated anaerobic infections may lead to use of inactive agents or overly broad-spectrum antibiotics. Current antimicrobial stewardship initiatives recognize the importance of narrow-spectrum antibiotics to minimize risk of adverse events and selective pressure for antimicrobial resistance.
Although we attempted to confirm the identification of the anaerobic isolates via commercially available methods, it was not until we performed genetic testing that we were able verify the isolates as B fragilis. Furthermore, earlier susceptibility testing would have allowed for more narrow-targeted antimicrobial therapy and could have potentially prevented our patient’s readmission and use of ertapenem, despite its > 98% susceptibility rates against B fragilis.13,17
All of the B fragilis isolates carried the cepA gene, which is a cephalosporinase that encodes for resistance to cephalosporins and aminopenicillins but not to ß-lactam ß-lactamase inhibitor combinations.13 Although not a substitution for susceptibility analysis, genetic testing showed that all of the isolates carried a nonsynonymous mutation from serine to a phenylalanine at amino acid position 82 (S82F) in the gyrA gene. The S82F mutation has been implicated in fluoroquinolone resistance, via inhibition of substrate–target recognition and binding between fluoroquinolones and the target topoisomerase protein,18 and may potentially explain why our patient clinically worsened while on moxifloxacin monotherapy. Although moxifloxacin susceptibility was not performed, susceptibility rates remain highly variable, ranging from 50% to 70% for B fragilis.13,15,16
It is important to note that the metronidazole the patient received during his first hospital admission could have sterilized the vertebral body without completely eradicating the microbe; thus could explain his clinical worsening while on moxifloxacin monotherapy despite no growth from the repeat biopsy culture. Our rationale for initially continuing moxifloxacin was based on its excellent bioavailability and bone penetration properties. Additionally, of the fluoroquinolones it has the most reliable anaerobic activity and is the only one recommended as monotherapy for complicated intraabdominal infections.19 However, guidelines recommend avoiding its use in patients who have received a fluoroquinolone in the past 90 days or at institutions with high rates of resistance. At our institution Escherichia coli has a > 90% susceptibility rate to fluoroquinolones. Given this rate and our concern that the patient had a polymicrobial infection, we felt that moxifloxacin would provide appropriate anaerobic and aerobic coverage, especially since he had no previous fluoroquinolone exposure.
Additionally, none of the isolates carried the nim or bft toxin genes. Although the nim gene is associated with metronidazole resistance,its presence does not invariably result in resistant strains of B fragilis; in fact, metronidazole resistance is relatively uncommon, with the majority of B fragilis showing < 1% resistance, based on CLSI breakpoints (≥ 32 mg/L).13,20,21 However, one recent epidemiologic study on anaerobic wound isolates from Iraq and Afghanistan casualties found that 12% (2/17) of B fragilis isolates were resistant to metronidazole.15 Given the improvement of the patient’s symptoms while on metronidazole, it is likely that the B fragilis was susceptible. Nevertheless, susceptibility testing with minimum inhibitory concentrations is necessary to verify this result. Also, although enterotoxigenic strains of B fragilis have been associated with bloodstream infections, our patient’s isolates lacked the 3 subtypes of B fragilis enterotoxin gene.22
Conclusions
We report a case of B fragilis bacteremia and vertebral osteomyelitis complicated by challenges in anaerobic identification and sensitivities that led to brief use of a possibly inactive antimicrobial and the subsequent use of carbapenem therapy, which may have been avoided if susceptibility testing were more readily available. This case led to changes in our hospital’s processing of anaerobic isolates to include susceptibility testing on request.
Acknowledgments
We thank Keith Thompson, MD (staff pathologist, Naval Medical Center Portsmouth Virginia), for providing the pathology images from the initial vertebral biopsy, and Dr. Kate Hinkle (director, Multidrug-Resistant Organism Repository and Surveillance Network, Silver Spring, Maryland ) for providing the whole genome sequencing results from the B fragilis isolates.
1. Zimmerli W. Vertebral osteomyelitis. N Eng J Med. 2010;362(11):1022-1029.
2. Chazan B, Strahilevitz J, Millgram MA, Kaufmann S, Raz R. Bacteroides fragilis vertebral osteomyelitis secondary to anal dilatation. Spine (Phila PA 1976). 2001;26(16):E377-E378.
3. Kierzkowska M, Pedzisz P, Babiak I, et al. Orthopedic infections caused by obligatory anaerobic Gram-negative rods: report of two cases. Med Microbiol Immunol. 2017;206(5):363-366.
4. McHenry M, Easley K, Locker G. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis. 2002;34(10):1342-1350.
5. Raff MJ, Melo JC. Anaerobic osteomyelitis. Medicine (Baltimore).1978;57(1):83-103.
6. Lewis R, Sutter V, Finegold S. Bone infections involving anaerobic bacteria. Medicine (Baltimore). 1978;57(1):279-305.
7. Brook I. The role of anaerobic bacteria in bacteremia. Anaerobe. 2010;16(3):183-189.
8. Lassmann B, Gustafson DR, Wood CM, Rosenblatt JE. Reemergence of anaerobic bacteremia. Clin Infect Dis. 2007;44(7):895-900.
9. Lazarovitch T, Freimann S, Shapira G, Blank H. Decrease in anaerobe-related bacteraemias and increase in Bacteroides species isolation rate from 1998 to 2007: a retrospective study. Anaerobe. 2010;16(3):201-205.
10. Keukeleire S, Wybo I, Naessens A, et al. Anaerobic bacteraemia: a 10-year retrospective epidemiological survey. Anaerobe. 2016;39:54-59.
11. Goldstein EJC, Citron DM, Goldman PJ, Goldman RJ. National hospital survey of anaerobic culture and susceptibility methods: III. Anaerobe. 2008;14(2):68-72.
12. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-e77.
13. Schuetz AN. Antimicrobial resistance and susceptibility testing of anaerobic bacteria. Antimicr Resist. 2014;59(5):698-705.
14. Clinical and Laboratory Standards Institute. M11-A8: Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard. 8th ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.
15. White B, Mende K, Weintrob A, et al; Infectious Disease Clinical Research Program Trauma Infectious Disease Outcome Study Group. Epidemiology and antimicrobial susceptibilities of wound isolates of obligate anaerobes from combat casualties. Diagn Mircrobiol Infect Dis. 2016;84(2):144-150.
16. Hastey CJ, Boyd H, Schuetz AN, et al; Ad Hoc Working Group on Antimicrobial Susceptibility Testing of Anaerobic Bacteria of CLSI. Changes in the antibiotic susceptibility of anaerobic bacteria from 2007-2009 to 2010-2012 based on the CLSI methodology. Anaerobe. 2016;42:27-30.
17. Brook I, Wexler HM, Goldstein EJC. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev. 2013;26(3):526-546.
18. Pumbwe L, Wareham D, Aduse-Opoku J, Brazier JS, Wexler HM. Genetic analysis of mechanisms of multidrug resistance in a clinical isolate of Bacteroides fragilis. Clin Microbiol Infect. 2007;13(2):183-189.
19. Solomkin J, Mazuski J, Bradley J, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164.
20. Breuil J, Dublanchet A, Truffaut N, Sebald M. Transferable 5-nitroimidazole resistance Bacteroides fragilis group. Plasmid. 1989;21(2):151-154.
21. Nagy E, Urbán E, Nord CE; ESCMID Study Group on Antimicrobial Resistance in Anaerobic Bacteria. Antimicrobial susceptibility of Bacteroides fragilis group isolates in Europe: 20 years of experience. Clin Microbiol Infect. 2011;17(3):371-379.
22. Avila-Campos M, Liu C, Song Y, Rowlinson M-C, Finegold SM. Determination of bft gene subtypes in Bacteroides fragilis clinical isolates. J Clin Microbiol. 2007;45(4):1336-1338.
Acute pyogenic vertebral osteomyelitis is often due to hematogenous spread of aerobic bacteria.1-4 Conversely, only 0.5% of anaerobic bacteremias lead to osteomyelitis.5 Anaerobic osteomyelitis typically results from the contiguous spread of polymicrobial infections through breaks in the gut mucosal barrier and involves the vertebral bodies in only 2% to 5% of cases.5,6 Although Bacteroides fragilis (B fragilis) is the most common anaerobic pathogen cultivated from blood, accounting for about half of all anaerobic blood isolates, it seldom leads to osteomyelitis.1,2,7-11 We report an uncommon case of B fragilis bacteremia and vertebral osteomyelitis confounded by uncertainties in anaerobic identification and susceptibilities.
Case Presentation
A healthy-appearing male aged 55 years presented to the Naval Medical Center Portsmouth (NMCP) with subacute low back pain and fevers of 103 °F for > 3 weeks. While traveling 4 weeks prior, he completed a course of oseltamivir for influenza B infection; afterward, he was diagnosed with community-acquired pneumonia and treated with a dose of ceftriaxone and a 7-day course of doxycycline. The patient presented to the same facility a week later for low back pain and nonresolving respiratory symptoms, and his therapy was changed to azithromycin, cefuroxime, prednisone, and inhalers. Additionally, after being treated for influenza, he developed constipation and hematochezia for which he did not seek care. The hematochezia was similar to a previous episode from an anal fissure 1 year prior that resolved with stool softeners. When he was finally seen at NMCP after 3 weeks of worsening back pain and fevers, lumbosacral magnetic resonance imaging (MRI) demonstrated vertebral osteomyelitis and discitis at L4-L5 and admitted to the hospital (Figure 1).
After a fluoroscopy-guided biopsy of the L4 vertebral body on hospital day 1, the patient was started on cefepime and vancomycin. The biopsy sample was inoculated onto solid media (blood agar, chocolate agar, and MacConkey agar) and incubated at 36 °C for 24 hours in a 5% CO2 atmosphere, as well as onto Shaedler agar with vitamin K and chopped meat glucose broth and incubated at 36 °C for 48 hours under anaerobic conditions. Metronidazole was added and vancomycin discontinued after 2 anaerobic blood culture vials obtained on hospital day 1, incubated in a Becton Dickinson BACTEC FX automated system, which demonstrated Gram-negative bacilli after 48 hours. The blood culture isolates demonstrated a > 99% probability of being identified as ß-lactamase positive Prevotella loescheii using Thermo Fischer Scientific RapID ANA II biochemical testing. Nitrocefinase discs were used to detect ß-lactamase activity.
The biopsy demonstrated nongranulomatous focal areas of necrotic bone and neutrophilia in a hematopoietic background consistent with acute osteomyelitis (Figure 2); on hospital day 4, ß-lactamase positive B fragilis grew from the bone culture. Additionally, 1 anaerobic vial from a surveillance blood culture set that was obtained on hospital day 3 grew ß-lactamasepositive B fragilis using the same identification methods. With these results he was thought to have a polymicrobial infection (B fragilis and Prevotella loescheii [P loescheii]) from a suspected bowel source based on his hematochezia and history of anal fissure. No aerobic, Gram-negative enterobacteriaceae were isolated, but he had previously been on cefuroxime, which has potential activity against these organisms, for ≥ 2 weeks prior to hospitalization and cultures. He was discharged on moxifloxacin and metronidazole pending final culture results, including requested anaerobic susceptibility testing.
At 1-week follow-up, both aerobic and anaerobic vials from surveillance blood cultures remained negative for any microbes, so antibiotics were deescalated to moxifloxacin monotherapy. However, after 3 days the patient was readmitted for increasing C-reactive protein (CRP) levels and intractable back pain with worsening bilateral radiculopathy. A repeat MRI demonstrated interval disease progression with near obliteration of the L4-L5 disc space and hyperenhancement of the prevertebral soft tissues and adjacent psoas musculature without focal rim-enhancing fluid collection (Figure 3). After repeat L4 biopsy, metronidazole was restarted and ertapenem added for enterobacteriaceae coverage, given the known B fragilis and potential suppression from previous cephalosporin therapy; moxifloxacin was discontinued. L4 biopsy cultures showed no growth, and CRP levels trended down from 154.2 mg/L (start of first admission) to 42.4 mg/L (start of second admission) to 14.9 mg/L (day of discharge) (reference range, 5-9.9 mg/L). He was discharged on ertapenem and metronidazole. He completed a 6-week course without further complication.
During antibiotic therapy he had an unremarkable colonoscopy, CRP normalized to 2.6 mg/L (reference range, 0-4.9 mg/L), and he underwent successful L4-L5 transforaminal lumbar interbody fusion 2 weeks after finishing antibiotics.
We retroactively sent both P loescheii isolates and the 1 B fragilis isolate that grew from the surveillance blood culture to the Multidrug-resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Army Institute of Research for identification confirmation and susceptibility analysis. Whole genome sequencing with single nucleotide polymorphism (SNP)-based analysis revealed all isolates were 100% identical and consistent with B fragilis and not P loescheii, based on clustering around other B fragilis sequences found in the National Center for Biotechnology Information (NCBI) Genbank database (Figure 4). All isolates carried the antibiotic resistance genes— cepA, sul(2), tetQ— encoding for possible resistance to cephalosporins, sulphonamides, and tetracyclines, respectively; as well as a point mutation in the gyrA gene (Ser82Phe). None of the isolates carried the nim gene, and screening for the 3 subtypes of B fragilis enterotoxin gene (bft-1, bft-2, bft-3) was negative. Eventual susceptibility testing at the Mayo Clinic several months after the conclusion of the case indicated that the B fragilis isolate was sensitive to piperacillin-tazobactam, ertapenem, clindamycin, and metronidazole; however, testing was not performed against moxifloxacin.
Discussion
In the era of growing antibiotic resistance patterns, antimicrobial stewardship programs recommend interventions to improve antimicrobial use through targeted narrow- spectrum antibiotics.12 The Clinical and Laboratory Standards Institute (CLSI) maintains guidelines on the major indications for anaerobic antimicrobial susceptibility testing (AST) to help direct narrow-targeted antimicrobial therapy. However, in a 2008 practice survey Goldstein and colleagues reported that less than half of US hospitals performed anaerobic AST, and only 21% of these facilities did it in-house, while the remainder sent out their isolates for testing.11-14 The CLSI major indications for AST include situations in which the selection of agents is important because of the (1) known resistance of a particular species; (2) confirmation of appropriate therapy for severe infections or for those that may require long-term therapy; (3) persistence of infection despite adequate treatment with an appropriate therapeutic regimen; and (4) difficulty in making empirical decisions based on precedent.14 Additionally, isolates from brain abscess, endocarditis, osteomyelitis, joint infection, infection of prosthetic devices or vascular grafts, bacteremia, and normally sterile body sites (unless contamination suspected) should be tested.14
Because of the lack of anaerobic AST, health care providers must base empiric treatment on reported sensitivities from the medical literature. Empiric selection of antimicrobials for anaerobic infections is made even more challenging by the increased rates of resistance reported in the literature, leading to recommendations to increase susceptibility testing to guide therapy.13,15,16 Empiric therapy of deep-seated anaerobic infections may lead to use of inactive agents or overly broad-spectrum antibiotics. Current antimicrobial stewardship initiatives recognize the importance of narrow-spectrum antibiotics to minimize risk of adverse events and selective pressure for antimicrobial resistance.
Although we attempted to confirm the identification of the anaerobic isolates via commercially available methods, it was not until we performed genetic testing that we were able verify the isolates as B fragilis. Furthermore, earlier susceptibility testing would have allowed for more narrow-targeted antimicrobial therapy and could have potentially prevented our patient’s readmission and use of ertapenem, despite its > 98% susceptibility rates against B fragilis.13,17
All of the B fragilis isolates carried the cepA gene, which is a cephalosporinase that encodes for resistance to cephalosporins and aminopenicillins but not to ß-lactam ß-lactamase inhibitor combinations.13 Although not a substitution for susceptibility analysis, genetic testing showed that all of the isolates carried a nonsynonymous mutation from serine to a phenylalanine at amino acid position 82 (S82F) in the gyrA gene. The S82F mutation has been implicated in fluoroquinolone resistance, via inhibition of substrate–target recognition and binding between fluoroquinolones and the target topoisomerase protein,18 and may potentially explain why our patient clinically worsened while on moxifloxacin monotherapy. Although moxifloxacin susceptibility was not performed, susceptibility rates remain highly variable, ranging from 50% to 70% for B fragilis.13,15,16
It is important to note that the metronidazole the patient received during his first hospital admission could have sterilized the vertebral body without completely eradicating the microbe; thus could explain his clinical worsening while on moxifloxacin monotherapy despite no growth from the repeat biopsy culture. Our rationale for initially continuing moxifloxacin was based on its excellent bioavailability and bone penetration properties. Additionally, of the fluoroquinolones it has the most reliable anaerobic activity and is the only one recommended as monotherapy for complicated intraabdominal infections.19 However, guidelines recommend avoiding its use in patients who have received a fluoroquinolone in the past 90 days or at institutions with high rates of resistance. At our institution Escherichia coli has a > 90% susceptibility rate to fluoroquinolones. Given this rate and our concern that the patient had a polymicrobial infection, we felt that moxifloxacin would provide appropriate anaerobic and aerobic coverage, especially since he had no previous fluoroquinolone exposure.
Additionally, none of the isolates carried the nim or bft toxin genes. Although the nim gene is associated with metronidazole resistance,its presence does not invariably result in resistant strains of B fragilis; in fact, metronidazole resistance is relatively uncommon, with the majority of B fragilis showing < 1% resistance, based on CLSI breakpoints (≥ 32 mg/L).13,20,21 However, one recent epidemiologic study on anaerobic wound isolates from Iraq and Afghanistan casualties found that 12% (2/17) of B fragilis isolates were resistant to metronidazole.15 Given the improvement of the patient’s symptoms while on metronidazole, it is likely that the B fragilis was susceptible. Nevertheless, susceptibility testing with minimum inhibitory concentrations is necessary to verify this result. Also, although enterotoxigenic strains of B fragilis have been associated with bloodstream infections, our patient’s isolates lacked the 3 subtypes of B fragilis enterotoxin gene.22
Conclusions
We report a case of B fragilis bacteremia and vertebral osteomyelitis complicated by challenges in anaerobic identification and sensitivities that led to brief use of a possibly inactive antimicrobial and the subsequent use of carbapenem therapy, which may have been avoided if susceptibility testing were more readily available. This case led to changes in our hospital’s processing of anaerobic isolates to include susceptibility testing on request.
Acknowledgments
We thank Keith Thompson, MD (staff pathologist, Naval Medical Center Portsmouth Virginia), for providing the pathology images from the initial vertebral biopsy, and Dr. Kate Hinkle (director, Multidrug-Resistant Organism Repository and Surveillance Network, Silver Spring, Maryland ) for providing the whole genome sequencing results from the B fragilis isolates.
Acute pyogenic vertebral osteomyelitis is often due to hematogenous spread of aerobic bacteria.1-4 Conversely, only 0.5% of anaerobic bacteremias lead to osteomyelitis.5 Anaerobic osteomyelitis typically results from the contiguous spread of polymicrobial infections through breaks in the gut mucosal barrier and involves the vertebral bodies in only 2% to 5% of cases.5,6 Although Bacteroides fragilis (B fragilis) is the most common anaerobic pathogen cultivated from blood, accounting for about half of all anaerobic blood isolates, it seldom leads to osteomyelitis.1,2,7-11 We report an uncommon case of B fragilis bacteremia and vertebral osteomyelitis confounded by uncertainties in anaerobic identification and susceptibilities.
Case Presentation
A healthy-appearing male aged 55 years presented to the Naval Medical Center Portsmouth (NMCP) with subacute low back pain and fevers of 103 °F for > 3 weeks. While traveling 4 weeks prior, he completed a course of oseltamivir for influenza B infection; afterward, he was diagnosed with community-acquired pneumonia and treated with a dose of ceftriaxone and a 7-day course of doxycycline. The patient presented to the same facility a week later for low back pain and nonresolving respiratory symptoms, and his therapy was changed to azithromycin, cefuroxime, prednisone, and inhalers. Additionally, after being treated for influenza, he developed constipation and hematochezia for which he did not seek care. The hematochezia was similar to a previous episode from an anal fissure 1 year prior that resolved with stool softeners. When he was finally seen at NMCP after 3 weeks of worsening back pain and fevers, lumbosacral magnetic resonance imaging (MRI) demonstrated vertebral osteomyelitis and discitis at L4-L5 and admitted to the hospital (Figure 1).
After a fluoroscopy-guided biopsy of the L4 vertebral body on hospital day 1, the patient was started on cefepime and vancomycin. The biopsy sample was inoculated onto solid media (blood agar, chocolate agar, and MacConkey agar) and incubated at 36 °C for 24 hours in a 5% CO2 atmosphere, as well as onto Shaedler agar with vitamin K and chopped meat glucose broth and incubated at 36 °C for 48 hours under anaerobic conditions. Metronidazole was added and vancomycin discontinued after 2 anaerobic blood culture vials obtained on hospital day 1, incubated in a Becton Dickinson BACTEC FX automated system, which demonstrated Gram-negative bacilli after 48 hours. The blood culture isolates demonstrated a > 99% probability of being identified as ß-lactamase positive Prevotella loescheii using Thermo Fischer Scientific RapID ANA II biochemical testing. Nitrocefinase discs were used to detect ß-lactamase activity.
The biopsy demonstrated nongranulomatous focal areas of necrotic bone and neutrophilia in a hematopoietic background consistent with acute osteomyelitis (Figure 2); on hospital day 4, ß-lactamase positive B fragilis grew from the bone culture. Additionally, 1 anaerobic vial from a surveillance blood culture set that was obtained on hospital day 3 grew ß-lactamasepositive B fragilis using the same identification methods. With these results he was thought to have a polymicrobial infection (B fragilis and Prevotella loescheii [P loescheii]) from a suspected bowel source based on his hematochezia and history of anal fissure. No aerobic, Gram-negative enterobacteriaceae were isolated, but he had previously been on cefuroxime, which has potential activity against these organisms, for ≥ 2 weeks prior to hospitalization and cultures. He was discharged on moxifloxacin and metronidazole pending final culture results, including requested anaerobic susceptibility testing.
At 1-week follow-up, both aerobic and anaerobic vials from surveillance blood cultures remained negative for any microbes, so antibiotics were deescalated to moxifloxacin monotherapy. However, after 3 days the patient was readmitted for increasing C-reactive protein (CRP) levels and intractable back pain with worsening bilateral radiculopathy. A repeat MRI demonstrated interval disease progression with near obliteration of the L4-L5 disc space and hyperenhancement of the prevertebral soft tissues and adjacent psoas musculature without focal rim-enhancing fluid collection (Figure 3). After repeat L4 biopsy, metronidazole was restarted and ertapenem added for enterobacteriaceae coverage, given the known B fragilis and potential suppression from previous cephalosporin therapy; moxifloxacin was discontinued. L4 biopsy cultures showed no growth, and CRP levels trended down from 154.2 mg/L (start of first admission) to 42.4 mg/L (start of second admission) to 14.9 mg/L (day of discharge) (reference range, 5-9.9 mg/L). He was discharged on ertapenem and metronidazole. He completed a 6-week course without further complication.
During antibiotic therapy he had an unremarkable colonoscopy, CRP normalized to 2.6 mg/L (reference range, 0-4.9 mg/L), and he underwent successful L4-L5 transforaminal lumbar interbody fusion 2 weeks after finishing antibiotics.
We retroactively sent both P loescheii isolates and the 1 B fragilis isolate that grew from the surveillance blood culture to the Multidrug-resistant Organism Repository and Surveillance Network (MRSN) at the Walter Reed Army Institute of Research for identification confirmation and susceptibility analysis. Whole genome sequencing with single nucleotide polymorphism (SNP)-based analysis revealed all isolates were 100% identical and consistent with B fragilis and not P loescheii, based on clustering around other B fragilis sequences found in the National Center for Biotechnology Information (NCBI) Genbank database (Figure 4). All isolates carried the antibiotic resistance genes— cepA, sul(2), tetQ— encoding for possible resistance to cephalosporins, sulphonamides, and tetracyclines, respectively; as well as a point mutation in the gyrA gene (Ser82Phe). None of the isolates carried the nim gene, and screening for the 3 subtypes of B fragilis enterotoxin gene (bft-1, bft-2, bft-3) was negative. Eventual susceptibility testing at the Mayo Clinic several months after the conclusion of the case indicated that the B fragilis isolate was sensitive to piperacillin-tazobactam, ertapenem, clindamycin, and metronidazole; however, testing was not performed against moxifloxacin.
Discussion
In the era of growing antibiotic resistance patterns, antimicrobial stewardship programs recommend interventions to improve antimicrobial use through targeted narrow- spectrum antibiotics.12 The Clinical and Laboratory Standards Institute (CLSI) maintains guidelines on the major indications for anaerobic antimicrobial susceptibility testing (AST) to help direct narrow-targeted antimicrobial therapy. However, in a 2008 practice survey Goldstein and colleagues reported that less than half of US hospitals performed anaerobic AST, and only 21% of these facilities did it in-house, while the remainder sent out their isolates for testing.11-14 The CLSI major indications for AST include situations in which the selection of agents is important because of the (1) known resistance of a particular species; (2) confirmation of appropriate therapy for severe infections or for those that may require long-term therapy; (3) persistence of infection despite adequate treatment with an appropriate therapeutic regimen; and (4) difficulty in making empirical decisions based on precedent.14 Additionally, isolates from brain abscess, endocarditis, osteomyelitis, joint infection, infection of prosthetic devices or vascular grafts, bacteremia, and normally sterile body sites (unless contamination suspected) should be tested.14
Because of the lack of anaerobic AST, health care providers must base empiric treatment on reported sensitivities from the medical literature. Empiric selection of antimicrobials for anaerobic infections is made even more challenging by the increased rates of resistance reported in the literature, leading to recommendations to increase susceptibility testing to guide therapy.13,15,16 Empiric therapy of deep-seated anaerobic infections may lead to use of inactive agents or overly broad-spectrum antibiotics. Current antimicrobial stewardship initiatives recognize the importance of narrow-spectrum antibiotics to minimize risk of adverse events and selective pressure for antimicrobial resistance.
Although we attempted to confirm the identification of the anaerobic isolates via commercially available methods, it was not until we performed genetic testing that we were able verify the isolates as B fragilis. Furthermore, earlier susceptibility testing would have allowed for more narrow-targeted antimicrobial therapy and could have potentially prevented our patient’s readmission and use of ertapenem, despite its > 98% susceptibility rates against B fragilis.13,17
All of the B fragilis isolates carried the cepA gene, which is a cephalosporinase that encodes for resistance to cephalosporins and aminopenicillins but not to ß-lactam ß-lactamase inhibitor combinations.13 Although not a substitution for susceptibility analysis, genetic testing showed that all of the isolates carried a nonsynonymous mutation from serine to a phenylalanine at amino acid position 82 (S82F) in the gyrA gene. The S82F mutation has been implicated in fluoroquinolone resistance, via inhibition of substrate–target recognition and binding between fluoroquinolones and the target topoisomerase protein,18 and may potentially explain why our patient clinically worsened while on moxifloxacin monotherapy. Although moxifloxacin susceptibility was not performed, susceptibility rates remain highly variable, ranging from 50% to 70% for B fragilis.13,15,16
It is important to note that the metronidazole the patient received during his first hospital admission could have sterilized the vertebral body without completely eradicating the microbe; thus could explain his clinical worsening while on moxifloxacin monotherapy despite no growth from the repeat biopsy culture. Our rationale for initially continuing moxifloxacin was based on its excellent bioavailability and bone penetration properties. Additionally, of the fluoroquinolones it has the most reliable anaerobic activity and is the only one recommended as monotherapy for complicated intraabdominal infections.19 However, guidelines recommend avoiding its use in patients who have received a fluoroquinolone in the past 90 days or at institutions with high rates of resistance. At our institution Escherichia coli has a > 90% susceptibility rate to fluoroquinolones. Given this rate and our concern that the patient had a polymicrobial infection, we felt that moxifloxacin would provide appropriate anaerobic and aerobic coverage, especially since he had no previous fluoroquinolone exposure.
Additionally, none of the isolates carried the nim or bft toxin genes. Although the nim gene is associated with metronidazole resistance,its presence does not invariably result in resistant strains of B fragilis; in fact, metronidazole resistance is relatively uncommon, with the majority of B fragilis showing < 1% resistance, based on CLSI breakpoints (≥ 32 mg/L).13,20,21 However, one recent epidemiologic study on anaerobic wound isolates from Iraq and Afghanistan casualties found that 12% (2/17) of B fragilis isolates were resistant to metronidazole.15 Given the improvement of the patient’s symptoms while on metronidazole, it is likely that the B fragilis was susceptible. Nevertheless, susceptibility testing with minimum inhibitory concentrations is necessary to verify this result. Also, although enterotoxigenic strains of B fragilis have been associated with bloodstream infections, our patient’s isolates lacked the 3 subtypes of B fragilis enterotoxin gene.22
Conclusions
We report a case of B fragilis bacteremia and vertebral osteomyelitis complicated by challenges in anaerobic identification and sensitivities that led to brief use of a possibly inactive antimicrobial and the subsequent use of carbapenem therapy, which may have been avoided if susceptibility testing were more readily available. This case led to changes in our hospital’s processing of anaerobic isolates to include susceptibility testing on request.
Acknowledgments
We thank Keith Thompson, MD (staff pathologist, Naval Medical Center Portsmouth Virginia), for providing the pathology images from the initial vertebral biopsy, and Dr. Kate Hinkle (director, Multidrug-Resistant Organism Repository and Surveillance Network, Silver Spring, Maryland ) for providing the whole genome sequencing results from the B fragilis isolates.
1. Zimmerli W. Vertebral osteomyelitis. N Eng J Med. 2010;362(11):1022-1029.
2. Chazan B, Strahilevitz J, Millgram MA, Kaufmann S, Raz R. Bacteroides fragilis vertebral osteomyelitis secondary to anal dilatation. Spine (Phila PA 1976). 2001;26(16):E377-E378.
3. Kierzkowska M, Pedzisz P, Babiak I, et al. Orthopedic infections caused by obligatory anaerobic Gram-negative rods: report of two cases. Med Microbiol Immunol. 2017;206(5):363-366.
4. McHenry M, Easley K, Locker G. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis. 2002;34(10):1342-1350.
5. Raff MJ, Melo JC. Anaerobic osteomyelitis. Medicine (Baltimore).1978;57(1):83-103.
6. Lewis R, Sutter V, Finegold S. Bone infections involving anaerobic bacteria. Medicine (Baltimore). 1978;57(1):279-305.
7. Brook I. The role of anaerobic bacteria in bacteremia. Anaerobe. 2010;16(3):183-189.
8. Lassmann B, Gustafson DR, Wood CM, Rosenblatt JE. Reemergence of anaerobic bacteremia. Clin Infect Dis. 2007;44(7):895-900.
9. Lazarovitch T, Freimann S, Shapira G, Blank H. Decrease in anaerobe-related bacteraemias and increase in Bacteroides species isolation rate from 1998 to 2007: a retrospective study. Anaerobe. 2010;16(3):201-205.
10. Keukeleire S, Wybo I, Naessens A, et al. Anaerobic bacteraemia: a 10-year retrospective epidemiological survey. Anaerobe. 2016;39:54-59.
11. Goldstein EJC, Citron DM, Goldman PJ, Goldman RJ. National hospital survey of anaerobic culture and susceptibility methods: III. Anaerobe. 2008;14(2):68-72.
12. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-e77.
13. Schuetz AN. Antimicrobial resistance and susceptibility testing of anaerobic bacteria. Antimicr Resist. 2014;59(5):698-705.
14. Clinical and Laboratory Standards Institute. M11-A8: Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard. 8th ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.
15. White B, Mende K, Weintrob A, et al; Infectious Disease Clinical Research Program Trauma Infectious Disease Outcome Study Group. Epidemiology and antimicrobial susceptibilities of wound isolates of obligate anaerobes from combat casualties. Diagn Mircrobiol Infect Dis. 2016;84(2):144-150.
16. Hastey CJ, Boyd H, Schuetz AN, et al; Ad Hoc Working Group on Antimicrobial Susceptibility Testing of Anaerobic Bacteria of CLSI. Changes in the antibiotic susceptibility of anaerobic bacteria from 2007-2009 to 2010-2012 based on the CLSI methodology. Anaerobe. 2016;42:27-30.
17. Brook I, Wexler HM, Goldstein EJC. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev. 2013;26(3):526-546.
18. Pumbwe L, Wareham D, Aduse-Opoku J, Brazier JS, Wexler HM. Genetic analysis of mechanisms of multidrug resistance in a clinical isolate of Bacteroides fragilis. Clin Microbiol Infect. 2007;13(2):183-189.
19. Solomkin J, Mazuski J, Bradley J, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164.
20. Breuil J, Dublanchet A, Truffaut N, Sebald M. Transferable 5-nitroimidazole resistance Bacteroides fragilis group. Plasmid. 1989;21(2):151-154.
21. Nagy E, Urbán E, Nord CE; ESCMID Study Group on Antimicrobial Resistance in Anaerobic Bacteria. Antimicrobial susceptibility of Bacteroides fragilis group isolates in Europe: 20 years of experience. Clin Microbiol Infect. 2011;17(3):371-379.
22. Avila-Campos M, Liu C, Song Y, Rowlinson M-C, Finegold SM. Determination of bft gene subtypes in Bacteroides fragilis clinical isolates. J Clin Microbiol. 2007;45(4):1336-1338.
1. Zimmerli W. Vertebral osteomyelitis. N Eng J Med. 2010;362(11):1022-1029.
2. Chazan B, Strahilevitz J, Millgram MA, Kaufmann S, Raz R. Bacteroides fragilis vertebral osteomyelitis secondary to anal dilatation. Spine (Phila PA 1976). 2001;26(16):E377-E378.
3. Kierzkowska M, Pedzisz P, Babiak I, et al. Orthopedic infections caused by obligatory anaerobic Gram-negative rods: report of two cases. Med Microbiol Immunol. 2017;206(5):363-366.
4. McHenry M, Easley K, Locker G. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis. 2002;34(10):1342-1350.
5. Raff MJ, Melo JC. Anaerobic osteomyelitis. Medicine (Baltimore).1978;57(1):83-103.
6. Lewis R, Sutter V, Finegold S. Bone infections involving anaerobic bacteria. Medicine (Baltimore). 1978;57(1):279-305.
7. Brook I. The role of anaerobic bacteria in bacteremia. Anaerobe. 2010;16(3):183-189.
8. Lassmann B, Gustafson DR, Wood CM, Rosenblatt JE. Reemergence of anaerobic bacteremia. Clin Infect Dis. 2007;44(7):895-900.
9. Lazarovitch T, Freimann S, Shapira G, Blank H. Decrease in anaerobe-related bacteraemias and increase in Bacteroides species isolation rate from 1998 to 2007: a retrospective study. Anaerobe. 2010;16(3):201-205.
10. Keukeleire S, Wybo I, Naessens A, et al. Anaerobic bacteraemia: a 10-year retrospective epidemiological survey. Anaerobe. 2016;39:54-59.
11. Goldstein EJC, Citron DM, Goldman PJ, Goldman RJ. National hospital survey of anaerobic culture and susceptibility methods: III. Anaerobe. 2008;14(2):68-72.
12. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-e77.
13. Schuetz AN. Antimicrobial resistance and susceptibility testing of anaerobic bacteria. Antimicr Resist. 2014;59(5):698-705.
14. Clinical and Laboratory Standards Institute. M11-A8: Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard. 8th ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.
15. White B, Mende K, Weintrob A, et al; Infectious Disease Clinical Research Program Trauma Infectious Disease Outcome Study Group. Epidemiology and antimicrobial susceptibilities of wound isolates of obligate anaerobes from combat casualties. Diagn Mircrobiol Infect Dis. 2016;84(2):144-150.
16. Hastey CJ, Boyd H, Schuetz AN, et al; Ad Hoc Working Group on Antimicrobial Susceptibility Testing of Anaerobic Bacteria of CLSI. Changes in the antibiotic susceptibility of anaerobic bacteria from 2007-2009 to 2010-2012 based on the CLSI methodology. Anaerobe. 2016;42:27-30.
17. Brook I, Wexler HM, Goldstein EJC. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev. 2013;26(3):526-546.
18. Pumbwe L, Wareham D, Aduse-Opoku J, Brazier JS, Wexler HM. Genetic analysis of mechanisms of multidrug resistance in a clinical isolate of Bacteroides fragilis. Clin Microbiol Infect. 2007;13(2):183-189.
19. Solomkin J, Mazuski J, Bradley J, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164.
20. Breuil J, Dublanchet A, Truffaut N, Sebald M. Transferable 5-nitroimidazole resistance Bacteroides fragilis group. Plasmid. 1989;21(2):151-154.
21. Nagy E, Urbán E, Nord CE; ESCMID Study Group on Antimicrobial Resistance in Anaerobic Bacteria. Antimicrobial susceptibility of Bacteroides fragilis group isolates in Europe: 20 years of experience. Clin Microbiol Infect. 2011;17(3):371-379.
22. Avila-Campos M, Liu C, Song Y, Rowlinson M-C, Finegold SM. Determination of bft gene subtypes in Bacteroides fragilis clinical isolates. J Clin Microbiol. 2007;45(4):1336-1338.
How to expand the APP role in a crisis
An opportunity to better appreciate the value of PAs, NPs
Advanced practice providers – physician assistants and nurse practitioners – at the 733-bed Emory University Hospital in Atlanta are playing an expanded role in the admission of patients into the hospital, particularly those suspected of having COVID-19.
Before the pandemic crisis, evaluation visits by the APP would have been reviewed on the same day by the supervising physician through an in-person encounter with the patient. The new protocol is not outside of scope-of-practice regulations for APPs in Georgia or of the hospital’s bylaws. But it offers a way to help limit the overall exposure of hospital staff to patients suspected of COVID-19 infection, and the total amount of time providers spend in such patients’ room. Just one provider now needs to meet the patient during the admissions process, while the attending physician can fulfill a requirement for seeing the patient within 24 hours during rounds the following day. Emergency encounters would still be done as needed.
These protocols point toward future conversations about the limits to APPs’ scope of practice, and whether more expansive approaches could be widely adopted once the current crisis is over, say advocates for the APPs’ role.
“Our APPs are primarily doing the admissions to the hospital of COVID patients and of non-COVID patients, as we’ve always done. But with COVID-infected or -suspected patients, we’re trying to minimize exposure for our providers,” explained Susan Ortiz, a certified PA, lead APP at Emory University Hospital. “In this way, we can also see more patients more efficiently.” Ms. Ortiz said she finds in talking to other APP leads in the Emory system that “each facility has its own culture and way of doing things. But for the most part, they’re all trying to do something to limit providers’ time in patients’ rooms.”
In response to the rapidly moving crisis, tactics to limit personnel in COVID patients’ rooms to the “absolutely essential” include gathering much of the needed history and other information requested from the patient by telephone, Ms. Ortiz said. This can be done either over the patient’s own cell phone or a phone placed in the room by hospital staff. Family members may be called to supplement this information, with the patient’s consent.
Once vital sign monitoring equipment is hooked up, it is possible to monitor the patient’s vital signs remotely without making frequent trips into the room. That way, in-person vital sign monitoring doesn’t need to happen routinely – at least not as often. One observation by clinicians on Ms. Ortiz’s team: listening for lung sounds with a stethoscope has not been shown to alter treatment for these patients. Once a chest X-ray shows structural changes in a patient’s lung, all lung exams are going to sound bad.
The admitting provider still needs to meet the patient in person for part of the admission visit and physical exam, but the amount of time spent in close personal contact with the patient can be much shorter, Ms. Ortiz said. For patients who are admitted, if there is a question about difficulty swallowing, they will see a speech pathologist, and if evidence of malnutrition, a nutritionist. “But we have to be extremely thoughtful about when people go into the room. So we are not ordering these ancillary services as routinely as we do during non-COVID times,” she said.
Appropriate levels of fear
Emory’s hospitalists are communicating daily about a rapidly changing situation. “We get a note by email every day, and we have a Dropbox account for downloading more information,” Ms. Ortiz said. A joint on-call system is used to provide backup coverage of APPs at the seven Emory hospitals. When replacement shifts need filling in a hurry, practitioners are able to obtain emergency credentials at any of the other hospitals. “It’s a voluntary process to sign up to be on-call,” Ms. Ortiz said. So far, that has been sufficient.
All staff have their own level of “appropriate fear” of this infection, Ms. Ortiz noted. “We have an extremely supportive group here to back up those of us who, for good reason, don’t want to be admitting the COVID patients.” Ms. Ortiz opted out of doing COVID admissions because her husband’s health places him at particular risk. “But with the cross-coverage we have, sometimes I’ll provide assistance when needed if a patient is suspected of being infected.” APPs are critical to Emory’s hospital medicine group – not ancillaries. “Everyone here feels that way. So we want to give them a lot of support. We’re all pitching in, doing it together,” she said.
“We said when we started with this, a couple of weeks before the surge started, that you could volunteer to see COVID patients,” said Emory hospitalist Jessica Nave, MD. “As we came to realize that the demand would be greater, we said you would need to opt out of seeing these patients, rather than opt in, and have a reason for doing so.” An example is pregnant staff, of which there seems to be a lot at Emory right now, Dr. Nave said, or those who are immunocompromised for other reasons. Those who don’t opt out are seeing the majority of the COVID patients, depending on actual need.
Dr. Nave is married to another hospitalist at Emory. “We can’t isolate from each other or our children. He and I have a regimented protocol for how we handle the risk, which includes taking off our shoes and clothes in the garage, showering and wiping down every place we might have touched. But those steps are not guarantees.” Other staff at Emory are isolating from their families for weeks at a time. Emory has a conference hotel offering discounted rates to staff. Nine physicians at Emory have been tested for the infection based on presenting symptoms, but at press time none had tested positive.
Streamlining code blue
Another area in which Emory has revised its policies in response to COVID-19 is for in-hospital cardiac arrest code response. Codes are inherently unpredictable, and crowd control has always been an issue for them, Dr. Nave said. “Historically, you could have 15 or more people show up when a code was called. Now, more than ever, we need to limit the number of people involved, for the same reason, avoiding unnecessary patient contact.”
The hospital’s Resuscitation Committee took the lead on developing a new policy, approved by the its Critical Care Committee and COVID Task Force, to limit the number of professionals in the room when running a code to an essential six: two doing chest compression, two managing airways, a code leader, and a critical care nurse. Outside the patient’s door, wearing the same personal protective equipment (PPE), are a pharmacist, recorder, and runner. “If you’re not one of those nine, you don’t need to be involved and should leave the area,” Dr. Nave said.
Staff have been instructed that they need to don appropriate PPE, including gown, mask, and eye wear, before entering the room for a code – even if that delays the start of intervention. “We’ve also made a code kit for each unit with quickly accessible gowns and masks. It should be used only for code blues.”
Increasing flexibility for the team
PAs and NPs in other locations are also exploring opportunities for gearing up to play larger roles in hospital care in the current crisis situation. The American Association of Physician Assistants has urged all U.S. governors to issue executive orders to waive state-specific licensing requirements for physician supervision or collaboration during the crisis, in order to increase flexibility of health care teams to deploy APPs.
AAPA believes the supervisory requirement is the biggest current barrier to mobilizing PAs and NPs. That includes those who have been furloughed from outpatient or other settings but are limited in their ability to contribute to the COVID crisis by the need to sign a supervision agreement with a physician at a new hospital.
The crisis is creating an opportunity to better appreciate the value PAs and NPs bring to health care, said Tracy Cardin, ACNP-BC, SFHM, vice president for advanced practice providers at Sound Physicians, a national hospitalist company based in Tacoma, Wash. The company recently sent a memo to the leadership of hospital sites at which it has contracts, requesting suspension of the hospitals’ requirements for a daily physician supervisory visit for APPs – which can be a hurdle when trying to leverage all hands on deck in the crisis.
NPs and PAs are stepping up and volunteering for COVID patients, Ms. Cardin said. Some have even taken leaves from their jobs to go to New York to help out at the epicenter of the U.S. crisis. “They want to make a difference. We’ve been deploying nonhospital medicine APPs from surgery, primary care, and elsewhere, embedding them on the hospital medicine team.”
Before the crisis, APPs at Sound Physicians weren’t always able to practice at the top of their licenses, depending on the hospital setting, added Alicia Scheffer, CNP, the company’s Great Lakes regional director for APPs. “Then COVID-19 showed up and really expedited conversations about how to maximize caseloads using APPs and about the fear of failing patients due to lack of capacity.”
In several locales, Sound Physicians is using quarantined providers to do telephone triage, or staffing ICUs with APPs backed up by telemedicine. “In APP-led ICUs, where the nurses are leading, they are intubating patients, placing central lines, things we weren’t allowed to do before,” Ms. Scheffer said.
A spirit of improvisation
There is a lot of tension at Emory University Hospital these days, reflecting the fears and uncertainties about the crisis, Dr. Nave said. “But there’s also a strangely powerful camaraderie like I’ve never seen before. When you walk onto the COVID units, you feel immediately bonded to the nurses, the techs, the phlebotomists. And you feel like you could talk about anything.”
Changes such as those made at Emory, have been talked about for a while, for example when hospitalists are having a busy night, she said. “But because this is a big cultural change, some physicians resisted it. We trust our APPs. But if the doctor’s name is on a patient chart, they want to see the patient – just for their own comfort level.”
Ms. Ortiz thinks the experience with the COVID crisis could help to advance the conversation about the appropriate role for APPs and their scope of practice in hospital medicine, once the current crisis has passed. “People were used to always doing things a certain way. This experience, hopefully, will get us to the point where attending physicians have more comfort with the APP’s ability to act autonomously,” she said.
“We’ve also talked about piloting telemedicine examinations using Zoom,” Dr. Nave added. “It’s making us think a lot of remote cross-coverage could be done that way. We’ve talked about using the hospital’s iPads with patients. This crisis really makes you think you want to innovate, in a spirit of improvisation,” she said. “Now is the time to try some of these things.”
Editors note: During the COVID-19 pandemic, many hospitals are seeing unprecedented volumes of patients requiring hospital medicine groups to stretch their current resources and recruit providers from outside their groups to bolster their inpatient services. The Society of Hospital Medicine has put together the following stepwise guide for onboarding traditional outpatient and subspecialty-based providers to work on general medicine wards: COVID-19 nonhospitalist onboarding resources.
An opportunity to better appreciate the value of PAs, NPs
An opportunity to better appreciate the value of PAs, NPs
Advanced practice providers – physician assistants and nurse practitioners – at the 733-bed Emory University Hospital in Atlanta are playing an expanded role in the admission of patients into the hospital, particularly those suspected of having COVID-19.
Before the pandemic crisis, evaluation visits by the APP would have been reviewed on the same day by the supervising physician through an in-person encounter with the patient. The new protocol is not outside of scope-of-practice regulations for APPs in Georgia or of the hospital’s bylaws. But it offers a way to help limit the overall exposure of hospital staff to patients suspected of COVID-19 infection, and the total amount of time providers spend in such patients’ room. Just one provider now needs to meet the patient during the admissions process, while the attending physician can fulfill a requirement for seeing the patient within 24 hours during rounds the following day. Emergency encounters would still be done as needed.
These protocols point toward future conversations about the limits to APPs’ scope of practice, and whether more expansive approaches could be widely adopted once the current crisis is over, say advocates for the APPs’ role.
“Our APPs are primarily doing the admissions to the hospital of COVID patients and of non-COVID patients, as we’ve always done. But with COVID-infected or -suspected patients, we’re trying to minimize exposure for our providers,” explained Susan Ortiz, a certified PA, lead APP at Emory University Hospital. “In this way, we can also see more patients more efficiently.” Ms. Ortiz said she finds in talking to other APP leads in the Emory system that “each facility has its own culture and way of doing things. But for the most part, they’re all trying to do something to limit providers’ time in patients’ rooms.”
In response to the rapidly moving crisis, tactics to limit personnel in COVID patients’ rooms to the “absolutely essential” include gathering much of the needed history and other information requested from the patient by telephone, Ms. Ortiz said. This can be done either over the patient’s own cell phone or a phone placed in the room by hospital staff. Family members may be called to supplement this information, with the patient’s consent.
Once vital sign monitoring equipment is hooked up, it is possible to monitor the patient’s vital signs remotely without making frequent trips into the room. That way, in-person vital sign monitoring doesn’t need to happen routinely – at least not as often. One observation by clinicians on Ms. Ortiz’s team: listening for lung sounds with a stethoscope has not been shown to alter treatment for these patients. Once a chest X-ray shows structural changes in a patient’s lung, all lung exams are going to sound bad.
The admitting provider still needs to meet the patient in person for part of the admission visit and physical exam, but the amount of time spent in close personal contact with the patient can be much shorter, Ms. Ortiz said. For patients who are admitted, if there is a question about difficulty swallowing, they will see a speech pathologist, and if evidence of malnutrition, a nutritionist. “But we have to be extremely thoughtful about when people go into the room. So we are not ordering these ancillary services as routinely as we do during non-COVID times,” she said.
Appropriate levels of fear
Emory’s hospitalists are communicating daily about a rapidly changing situation. “We get a note by email every day, and we have a Dropbox account for downloading more information,” Ms. Ortiz said. A joint on-call system is used to provide backup coverage of APPs at the seven Emory hospitals. When replacement shifts need filling in a hurry, practitioners are able to obtain emergency credentials at any of the other hospitals. “It’s a voluntary process to sign up to be on-call,” Ms. Ortiz said. So far, that has been sufficient.
All staff have their own level of “appropriate fear” of this infection, Ms. Ortiz noted. “We have an extremely supportive group here to back up those of us who, for good reason, don’t want to be admitting the COVID patients.” Ms. Ortiz opted out of doing COVID admissions because her husband’s health places him at particular risk. “But with the cross-coverage we have, sometimes I’ll provide assistance when needed if a patient is suspected of being infected.” APPs are critical to Emory’s hospital medicine group – not ancillaries. “Everyone here feels that way. So we want to give them a lot of support. We’re all pitching in, doing it together,” she said.
“We said when we started with this, a couple of weeks before the surge started, that you could volunteer to see COVID patients,” said Emory hospitalist Jessica Nave, MD. “As we came to realize that the demand would be greater, we said you would need to opt out of seeing these patients, rather than opt in, and have a reason for doing so.” An example is pregnant staff, of which there seems to be a lot at Emory right now, Dr. Nave said, or those who are immunocompromised for other reasons. Those who don’t opt out are seeing the majority of the COVID patients, depending on actual need.
Dr. Nave is married to another hospitalist at Emory. “We can’t isolate from each other or our children. He and I have a regimented protocol for how we handle the risk, which includes taking off our shoes and clothes in the garage, showering and wiping down every place we might have touched. But those steps are not guarantees.” Other staff at Emory are isolating from their families for weeks at a time. Emory has a conference hotel offering discounted rates to staff. Nine physicians at Emory have been tested for the infection based on presenting symptoms, but at press time none had tested positive.
Streamlining code blue
Another area in which Emory has revised its policies in response to COVID-19 is for in-hospital cardiac arrest code response. Codes are inherently unpredictable, and crowd control has always been an issue for them, Dr. Nave said. “Historically, you could have 15 or more people show up when a code was called. Now, more than ever, we need to limit the number of people involved, for the same reason, avoiding unnecessary patient contact.”
The hospital’s Resuscitation Committee took the lead on developing a new policy, approved by the its Critical Care Committee and COVID Task Force, to limit the number of professionals in the room when running a code to an essential six: two doing chest compression, two managing airways, a code leader, and a critical care nurse. Outside the patient’s door, wearing the same personal protective equipment (PPE), are a pharmacist, recorder, and runner. “If you’re not one of those nine, you don’t need to be involved and should leave the area,” Dr. Nave said.
Staff have been instructed that they need to don appropriate PPE, including gown, mask, and eye wear, before entering the room for a code – even if that delays the start of intervention. “We’ve also made a code kit for each unit with quickly accessible gowns and masks. It should be used only for code blues.”
Increasing flexibility for the team
PAs and NPs in other locations are also exploring opportunities for gearing up to play larger roles in hospital care in the current crisis situation. The American Association of Physician Assistants has urged all U.S. governors to issue executive orders to waive state-specific licensing requirements for physician supervision or collaboration during the crisis, in order to increase flexibility of health care teams to deploy APPs.
AAPA believes the supervisory requirement is the biggest current barrier to mobilizing PAs and NPs. That includes those who have been furloughed from outpatient or other settings but are limited in their ability to contribute to the COVID crisis by the need to sign a supervision agreement with a physician at a new hospital.
The crisis is creating an opportunity to better appreciate the value PAs and NPs bring to health care, said Tracy Cardin, ACNP-BC, SFHM, vice president for advanced practice providers at Sound Physicians, a national hospitalist company based in Tacoma, Wash. The company recently sent a memo to the leadership of hospital sites at which it has contracts, requesting suspension of the hospitals’ requirements for a daily physician supervisory visit for APPs – which can be a hurdle when trying to leverage all hands on deck in the crisis.
NPs and PAs are stepping up and volunteering for COVID patients, Ms. Cardin said. Some have even taken leaves from their jobs to go to New York to help out at the epicenter of the U.S. crisis. “They want to make a difference. We’ve been deploying nonhospital medicine APPs from surgery, primary care, and elsewhere, embedding them on the hospital medicine team.”
Before the crisis, APPs at Sound Physicians weren’t always able to practice at the top of their licenses, depending on the hospital setting, added Alicia Scheffer, CNP, the company’s Great Lakes regional director for APPs. “Then COVID-19 showed up and really expedited conversations about how to maximize caseloads using APPs and about the fear of failing patients due to lack of capacity.”
In several locales, Sound Physicians is using quarantined providers to do telephone triage, or staffing ICUs with APPs backed up by telemedicine. “In APP-led ICUs, where the nurses are leading, they are intubating patients, placing central lines, things we weren’t allowed to do before,” Ms. Scheffer said.
A spirit of improvisation
There is a lot of tension at Emory University Hospital these days, reflecting the fears and uncertainties about the crisis, Dr. Nave said. “But there’s also a strangely powerful camaraderie like I’ve never seen before. When you walk onto the COVID units, you feel immediately bonded to the nurses, the techs, the phlebotomists. And you feel like you could talk about anything.”
Changes such as those made at Emory, have been talked about for a while, for example when hospitalists are having a busy night, she said. “But because this is a big cultural change, some physicians resisted it. We trust our APPs. But if the doctor’s name is on a patient chart, they want to see the patient – just for their own comfort level.”
Ms. Ortiz thinks the experience with the COVID crisis could help to advance the conversation about the appropriate role for APPs and their scope of practice in hospital medicine, once the current crisis has passed. “People were used to always doing things a certain way. This experience, hopefully, will get us to the point where attending physicians have more comfort with the APP’s ability to act autonomously,” she said.
“We’ve also talked about piloting telemedicine examinations using Zoom,” Dr. Nave added. “It’s making us think a lot of remote cross-coverage could be done that way. We’ve talked about using the hospital’s iPads with patients. This crisis really makes you think you want to innovate, in a spirit of improvisation,” she said. “Now is the time to try some of these things.”
Editors note: During the COVID-19 pandemic, many hospitals are seeing unprecedented volumes of patients requiring hospital medicine groups to stretch their current resources and recruit providers from outside their groups to bolster their inpatient services. The Society of Hospital Medicine has put together the following stepwise guide for onboarding traditional outpatient and subspecialty-based providers to work on general medicine wards: COVID-19 nonhospitalist onboarding resources.
Advanced practice providers – physician assistants and nurse practitioners – at the 733-bed Emory University Hospital in Atlanta are playing an expanded role in the admission of patients into the hospital, particularly those suspected of having COVID-19.
Before the pandemic crisis, evaluation visits by the APP would have been reviewed on the same day by the supervising physician through an in-person encounter with the patient. The new protocol is not outside of scope-of-practice regulations for APPs in Georgia or of the hospital’s bylaws. But it offers a way to help limit the overall exposure of hospital staff to patients suspected of COVID-19 infection, and the total amount of time providers spend in such patients’ room. Just one provider now needs to meet the patient during the admissions process, while the attending physician can fulfill a requirement for seeing the patient within 24 hours during rounds the following day. Emergency encounters would still be done as needed.
These protocols point toward future conversations about the limits to APPs’ scope of practice, and whether more expansive approaches could be widely adopted once the current crisis is over, say advocates for the APPs’ role.
“Our APPs are primarily doing the admissions to the hospital of COVID patients and of non-COVID patients, as we’ve always done. But with COVID-infected or -suspected patients, we’re trying to minimize exposure for our providers,” explained Susan Ortiz, a certified PA, lead APP at Emory University Hospital. “In this way, we can also see more patients more efficiently.” Ms. Ortiz said she finds in talking to other APP leads in the Emory system that “each facility has its own culture and way of doing things. But for the most part, they’re all trying to do something to limit providers’ time in patients’ rooms.”
In response to the rapidly moving crisis, tactics to limit personnel in COVID patients’ rooms to the “absolutely essential” include gathering much of the needed history and other information requested from the patient by telephone, Ms. Ortiz said. This can be done either over the patient’s own cell phone or a phone placed in the room by hospital staff. Family members may be called to supplement this information, with the patient’s consent.
Once vital sign monitoring equipment is hooked up, it is possible to monitor the patient’s vital signs remotely without making frequent trips into the room. That way, in-person vital sign monitoring doesn’t need to happen routinely – at least not as often. One observation by clinicians on Ms. Ortiz’s team: listening for lung sounds with a stethoscope has not been shown to alter treatment for these patients. Once a chest X-ray shows structural changes in a patient’s lung, all lung exams are going to sound bad.
The admitting provider still needs to meet the patient in person for part of the admission visit and physical exam, but the amount of time spent in close personal contact with the patient can be much shorter, Ms. Ortiz said. For patients who are admitted, if there is a question about difficulty swallowing, they will see a speech pathologist, and if evidence of malnutrition, a nutritionist. “But we have to be extremely thoughtful about when people go into the room. So we are not ordering these ancillary services as routinely as we do during non-COVID times,” she said.
Appropriate levels of fear
Emory’s hospitalists are communicating daily about a rapidly changing situation. “We get a note by email every day, and we have a Dropbox account for downloading more information,” Ms. Ortiz said. A joint on-call system is used to provide backup coverage of APPs at the seven Emory hospitals. When replacement shifts need filling in a hurry, practitioners are able to obtain emergency credentials at any of the other hospitals. “It’s a voluntary process to sign up to be on-call,” Ms. Ortiz said. So far, that has been sufficient.
All staff have their own level of “appropriate fear” of this infection, Ms. Ortiz noted. “We have an extremely supportive group here to back up those of us who, for good reason, don’t want to be admitting the COVID patients.” Ms. Ortiz opted out of doing COVID admissions because her husband’s health places him at particular risk. “But with the cross-coverage we have, sometimes I’ll provide assistance when needed if a patient is suspected of being infected.” APPs are critical to Emory’s hospital medicine group – not ancillaries. “Everyone here feels that way. So we want to give them a lot of support. We’re all pitching in, doing it together,” she said.
“We said when we started with this, a couple of weeks before the surge started, that you could volunteer to see COVID patients,” said Emory hospitalist Jessica Nave, MD. “As we came to realize that the demand would be greater, we said you would need to opt out of seeing these patients, rather than opt in, and have a reason for doing so.” An example is pregnant staff, of which there seems to be a lot at Emory right now, Dr. Nave said, or those who are immunocompromised for other reasons. Those who don’t opt out are seeing the majority of the COVID patients, depending on actual need.
Dr. Nave is married to another hospitalist at Emory. “We can’t isolate from each other or our children. He and I have a regimented protocol for how we handle the risk, which includes taking off our shoes and clothes in the garage, showering and wiping down every place we might have touched. But those steps are not guarantees.” Other staff at Emory are isolating from their families for weeks at a time. Emory has a conference hotel offering discounted rates to staff. Nine physicians at Emory have been tested for the infection based on presenting symptoms, but at press time none had tested positive.
Streamlining code blue
Another area in which Emory has revised its policies in response to COVID-19 is for in-hospital cardiac arrest code response. Codes are inherently unpredictable, and crowd control has always been an issue for them, Dr. Nave said. “Historically, you could have 15 or more people show up when a code was called. Now, more than ever, we need to limit the number of people involved, for the same reason, avoiding unnecessary patient contact.”
The hospital’s Resuscitation Committee took the lead on developing a new policy, approved by the its Critical Care Committee and COVID Task Force, to limit the number of professionals in the room when running a code to an essential six: two doing chest compression, two managing airways, a code leader, and a critical care nurse. Outside the patient’s door, wearing the same personal protective equipment (PPE), are a pharmacist, recorder, and runner. “If you’re not one of those nine, you don’t need to be involved and should leave the area,” Dr. Nave said.
Staff have been instructed that they need to don appropriate PPE, including gown, mask, and eye wear, before entering the room for a code – even if that delays the start of intervention. “We’ve also made a code kit for each unit with quickly accessible gowns and masks. It should be used only for code blues.”
Increasing flexibility for the team
PAs and NPs in other locations are also exploring opportunities for gearing up to play larger roles in hospital care in the current crisis situation. The American Association of Physician Assistants has urged all U.S. governors to issue executive orders to waive state-specific licensing requirements for physician supervision or collaboration during the crisis, in order to increase flexibility of health care teams to deploy APPs.
AAPA believes the supervisory requirement is the biggest current barrier to mobilizing PAs and NPs. That includes those who have been furloughed from outpatient or other settings but are limited in their ability to contribute to the COVID crisis by the need to sign a supervision agreement with a physician at a new hospital.
The crisis is creating an opportunity to better appreciate the value PAs and NPs bring to health care, said Tracy Cardin, ACNP-BC, SFHM, vice president for advanced practice providers at Sound Physicians, a national hospitalist company based in Tacoma, Wash. The company recently sent a memo to the leadership of hospital sites at which it has contracts, requesting suspension of the hospitals’ requirements for a daily physician supervisory visit for APPs – which can be a hurdle when trying to leverage all hands on deck in the crisis.
NPs and PAs are stepping up and volunteering for COVID patients, Ms. Cardin said. Some have even taken leaves from their jobs to go to New York to help out at the epicenter of the U.S. crisis. “They want to make a difference. We’ve been deploying nonhospital medicine APPs from surgery, primary care, and elsewhere, embedding them on the hospital medicine team.”
Before the crisis, APPs at Sound Physicians weren’t always able to practice at the top of their licenses, depending on the hospital setting, added Alicia Scheffer, CNP, the company’s Great Lakes regional director for APPs. “Then COVID-19 showed up and really expedited conversations about how to maximize caseloads using APPs and about the fear of failing patients due to lack of capacity.”
In several locales, Sound Physicians is using quarantined providers to do telephone triage, or staffing ICUs with APPs backed up by telemedicine. “In APP-led ICUs, where the nurses are leading, they are intubating patients, placing central lines, things we weren’t allowed to do before,” Ms. Scheffer said.
A spirit of improvisation
There is a lot of tension at Emory University Hospital these days, reflecting the fears and uncertainties about the crisis, Dr. Nave said. “But there’s also a strangely powerful camaraderie like I’ve never seen before. When you walk onto the COVID units, you feel immediately bonded to the nurses, the techs, the phlebotomists. And you feel like you could talk about anything.”
Changes such as those made at Emory, have been talked about for a while, for example when hospitalists are having a busy night, she said. “But because this is a big cultural change, some physicians resisted it. We trust our APPs. But if the doctor’s name is on a patient chart, they want to see the patient – just for their own comfort level.”
Ms. Ortiz thinks the experience with the COVID crisis could help to advance the conversation about the appropriate role for APPs and their scope of practice in hospital medicine, once the current crisis has passed. “People were used to always doing things a certain way. This experience, hopefully, will get us to the point where attending physicians have more comfort with the APP’s ability to act autonomously,” she said.
“We’ve also talked about piloting telemedicine examinations using Zoom,” Dr. Nave added. “It’s making us think a lot of remote cross-coverage could be done that way. We’ve talked about using the hospital’s iPads with patients. This crisis really makes you think you want to innovate, in a spirit of improvisation,” she said. “Now is the time to try some of these things.”
Editors note: During the COVID-19 pandemic, many hospitals are seeing unprecedented volumes of patients requiring hospital medicine groups to stretch their current resources and recruit providers from outside their groups to bolster their inpatient services. The Society of Hospital Medicine has put together the following stepwise guide for onboarding traditional outpatient and subspecialty-based providers to work on general medicine wards: COVID-19 nonhospitalist onboarding resources.