The current COVID-19 pandemic has raised substantial anxieties and fears for healthcare workers, many of which they have not previously encountered. Important ethical issues have arisen involving the tension between their duties to their patients and their duties to themselves and to their loved ones. While these fears and duties are not unique to physicians or to members of one specialty, this article will focus on hospitalists. In general, hospitalists have an obligation to care for patients even if this puts them at risk, but duties to patients may at times be constrained by duties to others. At the same time, hospitals have correlative obligations to protect their employees and mitigate risk. Balancing these duties requires weighing benefits and risks, often in the context of considerable uncertainty. At this current time, it is conceivable that the risks may become so great that caring for patients is no longer obligatory but becomes heroic.

Conflicting duties arise in a variety of ways. Hospitalists are at increased risk of contracting the virus, given workplace exposures. The risk of complications is even higher for those who are older or have chronic medical conditions. Further, the shortage of personal protective equipment (PPE) adds to the overall risk. Hospitalists may also have concerns about transmitting the virus to family members or friends, especially to those who are elderly or have comorbidities. Hospitalists may also become physically and emotionally exhausted as work and home demands increase. Concerns for the care of dependents adds to the stress as daycares and schools close and older relatives are isolated in their homes. Hospitalists who are single parents and those whose partners are also healthcare workers are especially affected. The duty to care, encumbered by the cumulative stressors, creates an environment ripe for conflict.

Hospitalists have a duty to expose themselves to some, albeit not unlimited, risks. There are different ways of characterizing this obligation.¹ Some base it in the knowledge and power differential between physicians and patients, a differential increased by patients’ illnesses. Others frame it as a social contract: physicians receive certain benefits and privileges and, in accepting them, incur certain duties. Physicians practicing in the 1980s may recall a similar discussion about treating patients with the human immunodeficiency virus (HIV), while those who practiced in other countries in the early 2000s faced a similar conflict during the severe acute respiratory syndrome (SARS) epidemic, caused by another coronavirus.² The expectation of accepting risk may have been weakened in the last several decades, however, by the relative lack of risk in treating hospitalized patients in the United States.

Hospitalists’ duties to themselves and to their families are both intrinsically and instrumentally important. Being a hospitalist is not every hospitalist’s sole or predominant identity. They may also be adult children, spouses, and/or parents, or school board members or leaders in religious communities. Each of these roles entails its own duties and fulfilling them is also important. Effectuating them may, however, be more difficult because of the pandemic. Adult children may feel obligated to shop for their parents and parents of young children may have more childcare obligations. If no one else can fulfill these duties, they might take precedence over professional duties.

By fulfilling their duties to themselves and others, hospitalists may also be enabled to serve their patients. Unlike some discrete events, such as mass shootings or tornados, for which contingency and crisis standards of care may last for hours or days, we may be working under altered standards of care for weeks or months. (A contingency standard of care involves doing things differently in order to produce comparable clinical outcomes. A crisis standard of care is reached when it’s no longer possible to produce comparable clinical outcomes and the focus shifts from individual patient’s best interests or preferences to trying to save the most lives.³) It, therefore, is important we maintain our health and well-being by getting adequate sleep, eating well, and exercising.⁴ Arranging alternative child- and eldercare may reduce distractions at work and decrease the chance of needing to leave work unexpectedly.

In addressing these ethical issues, one of the key considerations is reducing the risks. We can reduce some risks ourselves while maintaining comparable outcomes to our conventional practices. I hope that it would go without saying, for example, that we should not work when we are sick. It is also important that we engage in adequate physical distancing whenever possible. It is important that physical distancing measures be applied equitably to all employees and that the actions hospitalists take to reduce their exposure do not disproportionately burden trainees or other types of providers. Consider, for example, having residents or nurse practitioners examine patients instead of the attending physician. This places subordinates at greater risk. Attending physicians, however, may have the best examination skills and their feedback is integral to trainees’ learning. Modeling a commitment to the duty to care and equitably accepting risk is exceptionally important as team members and leaders.

We can check in with one another and support each other emotionally. If some colleagues have substantially higher risks of complications, they may be assigned alternative duties with lower exposure risks. As a relatively young specialty, this may be more feasible for hospitalists than other specialties with a greater number of older practitioners. Care, however, should be taken to respect individuals’ privacy and confidentiality.

Minimizing risk is also a responsibility of hospitals and the local, state, and federal government. They have crucial roles in, for example, establishing adequate infection control policies and securing sufficient PPE. Many institutions have already moved to contingency standards of care to conserve PPE.⁵ These efforts not only support the duty of reciprocity⁶ but also help maintain an adequate workforce by reducing sick leave. The government’s apparent failure to fulfill its obligation to stockpile and distribute adequate equipment is currently being acutely felt.⁷

There are other potential actions that facilities can take, such as providing scrubs, child- and eldercare, housing, or life insurance. Individuals may be concerned about infecting family members. There is unfortunately limited data about spread on objects or asymptomatic spread, but these are reasonable possibilities. Facilities can provide scrubs to employees who do not normally wear them to provide a further barrier between the facility and the employees’ homes. They can provide child and elder care. It has been wonderful to see local community organizations and groups of medical students provide childcare for healthcare workers and other essential employees.⁸ Healthcare facilities could also consider providing temporary housing to staff with family members at high risk of complications. During the Ebola outbreak, some facilities provided supplemental disability and life insurance to staff who volunteered to put themselves at risk to help assure that their families would be provided for if the staff member unfortunately contracted the virus and became disabled or died.

Reciprocal duties to healthcare workers in a crisis standard of care are unresolved. Establishing ethically and clinically sound ventilator triage criteria is complex.^9,10 Some argue that healthcare providers should have some degree of priority. One argument is that if they recover, they can return to work and save more lives. (Having individuals who have recovered and are theoretically immune treat patients without PPE is one proposed conservation strategy.) It is, however, unclear whether individuals are likely to recover in enough time to return to work while we are still in a crisis standard of care. A different argument is that healthcare workers should be given priority because they accepted risk. This assumes they were infected at work and not in the community. While this argument has merit, it could be influenced by or perceived to be influenced by self-interest. Prioritizing healthcare workers for scarce resources requires substantial community support.¹¹

While providers have a duty to accept some risks, this duty is not unlimited. The mitigation strategies may be unsuccessful, and the risks substantial. One can think of analogies in other fields. Firefighters, for example, expose themselves to risk to save lives and to protect property. They are trained to take calculated risks, considering the likelihood and type of benefit and the degree of risk, but not to be reckless. They will take greater risk to save a life than property, and less risk if the victim is unlikely to survive. Their obligation to accept risk is not unlimited. They may justifiably choose not to enter a building, which is at significant, imminent risk of collapse, to protect property. The same is true for physicians. They are obligated to expose themselves to some risk, but not at a high likelihood of serious injury or death. At some point the duty to care for patients becomes supererogatory; fulfilling the duty is no longer required but becomes optional and doing so is heroic.¹² Some facilities, for example, will not perform cardiopulmonary resuscitation under a crisis standard of care due to the high risk of exposure and the low likelihood of success.¹³

Weighing potential benefits and risk is difficult. This difficulty is exacerbated by uncertainty. Some decisions would be easier, for example, if there was better evidence regarding asymptomatic spread. Finally, the subjectivity of some of these decisions raises concerns about unconscious bias or self-interest. It is therefore valuable to make some decisions collectively rather than individually. In particular, it is important to include those with adequate situation awareness. Conversely, once decisions are made, it is valuable to communicate both the decision and its rationale, and to be open to revising them based on feedback.

Given the fear and uncertainty generated by the pandemic, some individuals may be tempted to act unethically. Individuals have, unfortunately, taken hospital supplies, such as masks and hand sanitizer, for household use, and healthcare providers have hoarded medications, such as hydroxychloroquine.¹⁴ Individuals may also be tempted to use PPE for encounters when it is not indicated. We should address these fears and anxieties in other ways, such as discussing them with colleagues, chaplains, social workers, or employee assistance programs. If you observe coworkers acting in a manner that appears to be unethical, it is important to address their behavior while still giving them the benefit of the doubt. If you do not receive a satisfactory response, you should utilize the appropriate chain of command.

Most hospitalists are encountering situations that they have not previously experienced in their careers. These situations generate significant fear and anxiety. Many of these situations involve tensions between our duties to our patients and our duties to ourselves and to our families and friends. This tension is heightened for individuals who are older or have chronic health conditions or have family members who are. While healthcare providers have an obligation to accept some risks, this duty is not unlimited. Hospitals, healthcare systems, and governments have reciprocal obligations to keep providers safe. It is important to think creatively about ways to minimize risk. Due to uncertainty and self-interest, it may be better to make decisions collectively and transparently.

The current COVID-19 pandemic has raised substantial anxieties and fears for healthcare workers, many of which they have not previously encountered. Important ethical issues have arisen involving the tension between their duties to their patients and their duties to themselves and to their loved ones. While these fears and duties are not unique to physicians or to members of one specialty, this article will focus on hospitalists. In general, hospitalists have an obligation to care for patients even if this puts them at risk, but duties to patients may at times be constrained by duties to others. At the same time, hospitals have correlative obligations to protect their employees and mitigate risk. Balancing these duties requires weighing benefits and risks, often in the context of considerable uncertainty. At this current time, it is conceivable that the risks may become so great that caring for patients is no longer obligatory but becomes heroic.

Conflicting duties arise in a variety of ways. Hospitalists are at increased risk of contracting the virus, given workplace exposures. The risk of complications is even higher for those who are older or have chronic medical conditions. Further, the shortage of personal protective equipment (PPE) adds to the overall risk. Hospitalists may also have concerns about transmitting the virus to family members or friends, especially to those who are elderly or have comorbidities. Hospitalists may also become physically and emotionally exhausted as work and home demands increase. Concerns for the care of dependents adds to the stress as daycares and schools close and older relatives are isolated in their homes. Hospitalists who are single parents and those whose partners are also healthcare workers are especially affected. The duty to care, encumbered by the cumulative stressors, creates an environment ripe for conflict.

Hospitalists have a duty to expose themselves to some, albeit not unlimited, risks. There are different ways of characterizing this obligation.¹ Some base it in the knowledge and power differential between physicians and patients, a differential increased by patients’ illnesses. Others frame it as a social contract: physicians receive certain benefits and privileges and, in accepting them, incur certain duties. Physicians practicing in the 1980s may recall a similar discussion about treating patients with the human immunodeficiency virus (HIV), while those who practiced in other countries in the early 2000s faced a similar conflict during the severe acute respiratory syndrome (SARS) epidemic, caused by another coronavirus.² The expectation of accepting risk may have been weakened in the last several decades, however, by the relative lack of risk in treating hospitalized patients in the United States.

Hospitalists’ duties to themselves and to their families are both intrinsically and instrumentally important. Being a hospitalist is not every hospitalist’s sole or predominant identity. They may also be adult children, spouses, and/or parents, or school board members or leaders in religious communities. Each of these roles entails its own duties and fulfilling them is also important. Effectuating them may, however, be more difficult because of the pandemic. Adult children may feel obligated to shop for their parents and parents of young children may have more childcare obligations. If no one else can fulfill these duties, they might take precedence over professional duties.

By fulfilling their duties to themselves and others, hospitalists may also be enabled to serve their patients. Unlike some discrete events, such as mass shootings or tornados, for which contingency and crisis standards of care may last for hours or days, we may be working under altered standards of care for weeks or months. (A contingency standard of care involves doing things differently in order to produce comparable clinical outcomes. A crisis standard of care is reached when it’s no longer possible to produce comparable clinical outcomes and the focus shifts from individual patient’s best interests or preferences to trying to save the most lives.³) It, therefore, is important we maintain our health and well-being by getting adequate sleep, eating well, and exercising.⁴ Arranging alternative child- and eldercare may reduce distractions at work and decrease the chance of needing to leave work unexpectedly.

In addressing these ethical issues, one of the key considerations is reducing the risks. We can reduce some risks ourselves while maintaining comparable outcomes to our conventional practices. I hope that it would go without saying, for example, that we should not work when we are sick. It is also important that we engage in adequate physical distancing whenever possible. It is important that physical distancing measures be applied equitably to all employees and that the actions hospitalists take to reduce their exposure do not disproportionately burden trainees or other types of providers. Consider, for example, having residents or nurse practitioners examine patients instead of the attending physician. This places subordinates at greater risk. Attending physicians, however, may have the best examination skills and their feedback is integral to trainees’ learning. Modeling a commitment to the duty to care and equitably accepting risk is exceptionally important as team members and leaders.

We can check in with one another and support each other emotionally. If some colleagues have substantially higher risks of complications, they may be assigned alternative duties with lower exposure risks. As a relatively young specialty, this may be more feasible for hospitalists than other specialties with a greater number of older practitioners. Care, however, should be taken to respect individuals’ privacy and confidentiality.

Minimizing risk is also a responsibility of hospitals and the local, state, and federal government. They have crucial roles in, for example, establishing adequate infection control policies and securing sufficient PPE. Many institutions have already moved to contingency standards of care to conserve PPE.⁵ These efforts not only support the duty of reciprocity⁶ but also help maintain an adequate workforce by reducing sick leave. The government’s apparent failure to fulfill its obligation to stockpile and distribute adequate equipment is currently being acutely felt.⁷

There are other potential actions that facilities can take, such as providing scrubs, child- and eldercare, housing, or life insurance. Individuals may be concerned about infecting family members. There is unfortunately limited data about spread on objects or asymptomatic spread, but these are reasonable possibilities. Facilities can provide scrubs to employees who do not normally wear them to provide a further barrier between the facility and the employees’ homes. They can provide child and elder care. It has been wonderful to see local community organizations and groups of medical students provide childcare for healthcare workers and other essential employees.⁸ Healthcare facilities could also consider providing temporary housing to staff with family members at high risk of complications. During the Ebola outbreak, some facilities provided supplemental disability and life insurance to staff who volunteered to put themselves at risk to help assure that their families would be provided for if the staff member unfortunately contracted the virus and became disabled or died.

Reciprocal duties to healthcare workers in a crisis standard of care are unresolved. Establishing ethically and clinically sound ventilator triage criteria is complex.^9,10 Some argue that healthcare providers should have some degree of priority. One argument is that if they recover, they can return to work and save more lives. (Having individuals who have recovered and are theoretically immune treat patients without PPE is one proposed conservation strategy.) It is, however, unclear whether individuals are likely to recover in enough time to return to work while we are still in a crisis standard of care. A different argument is that healthcare workers should be given priority because they accepted risk. This assumes they were infected at work and not in the community. While this argument has merit, it could be influenced by or perceived to be influenced by self-interest. Prioritizing healthcare workers for scarce resources requires substantial community support.¹¹

While providers have a duty to accept some risks, this duty is not unlimited. The mitigation strategies may be unsuccessful, and the risks substantial. One can think of analogies in other fields. Firefighters, for example, expose themselves to risk to save lives and to protect property. They are trained to take calculated risks, considering the likelihood and type of benefit and the degree of risk, but not to be reckless. They will take greater risk to save a life than property, and less risk if the victim is unlikely to survive. Their obligation to accept risk is not unlimited. They may justifiably choose not to enter a building, which is at significant, imminent risk of collapse, to protect property. The same is true for physicians. They are obligated to expose themselves to some risk, but not at a high likelihood of serious injury or death. At some point the duty to care for patients becomes supererogatory; fulfilling the duty is no longer required but becomes optional and doing so is heroic.¹² Some facilities, for example, will not perform cardiopulmonary resuscitation under a crisis standard of care due to the high risk of exposure and the low likelihood of success.¹³

Weighing potential benefits and risk is difficult. This difficulty is exacerbated by uncertainty. Some decisions would be easier, for example, if there was better evidence regarding asymptomatic spread. Finally, the subjectivity of some of these decisions raises concerns about unconscious bias or self-interest. It is therefore valuable to make some decisions collectively rather than individually. In particular, it is important to include those with adequate situation awareness. Conversely, once decisions are made, it is valuable to communicate both the decision and its rationale, and to be open to revising them based on feedback.

Given the fear and uncertainty generated by the pandemic, some individuals may be tempted to act unethically. Individuals have, unfortunately, taken hospital supplies, such as masks and hand sanitizer, for household use, and healthcare providers have hoarded medications, such as hydroxychloroquine.¹⁴ Individuals may also be tempted to use PPE for encounters when it is not indicated. We should address these fears and anxieties in other ways, such as discussing them with colleagues, chaplains, social workers, or employee assistance programs. If you observe coworkers acting in a manner that appears to be unethical, it is important to address their behavior while still giving them the benefit of the doubt. If you do not receive a satisfactory response, you should utilize the appropriate chain of command.

Most hospitalists are encountering situations that they have not previously experienced in their careers. These situations generate significant fear and anxiety. Many of these situations involve tensions between our duties to our patients and our duties to ourselves and to our families and friends. This tension is heightened for individuals who are older or have chronic health conditions or have family members who are. While healthcare providers have an obligation to accept some risks, this duty is not unlimited. Hospitals, healthcare systems, and governments have reciprocal obligations to keep providers safe. It is important to think creatively about ways to minimize risk. Due to uncertainty and self-interest, it may be better to make decisions collectively and transparently.

The current COVID-19 pandemic has raised substantial anxieties and fears for healthcare workers, many of which they have not previously encountered. Important ethical issues have arisen involving the tension between their duties to their patients and their duties to themselves and to their loved ones. While these fears and duties are not unique to physicians or to members of one specialty, this article will focus on hospitalists. In general, hospitalists have an obligation to care for patients even if this puts them at risk, but duties to patients may at times be constrained by duties to others. At the same time, hospitals have correlative obligations to protect their employees and mitigate risk. Balancing these duties requires weighing benefits and risks, often in the context of considerable uncertainty. At this current time, it is conceivable that the risks may become so great that caring for patients is no longer obligatory but becomes heroic.

Conflicting duties arise in a variety of ways. Hospitalists are at increased risk of contracting the virus, given workplace exposures. The risk of complications is even higher for those who are older or have chronic medical conditions. Further, the shortage of personal protective equipment (PPE) adds to the overall risk. Hospitalists may also have concerns about transmitting the virus to family members or friends, especially to those who are elderly or have comorbidities. Hospitalists may also become physically and emotionally exhausted as work and home demands increase. Concerns for the care of dependents adds to the stress as daycares and schools close and older relatives are isolated in their homes. Hospitalists who are single parents and those whose partners are also healthcare workers are especially affected. The duty to care, encumbered by the cumulative stressors, creates an environment ripe for conflict.

Hospitalists have a duty to expose themselves to some, albeit not unlimited, risks. There are different ways of characterizing this obligation.¹ Some base it in the knowledge and power differential between physicians and patients, a differential increased by patients’ illnesses. Others frame it as a social contract: physicians receive certain benefits and privileges and, in accepting them, incur certain duties. Physicians practicing in the 1980s may recall a similar discussion about treating patients with the human immunodeficiency virus (HIV), while those who practiced in other countries in the early 2000s faced a similar conflict during the severe acute respiratory syndrome (SARS) epidemic, caused by another coronavirus.² The expectation of accepting risk may have been weakened in the last several decades, however, by the relative lack of risk in treating hospitalized patients in the United States.

Hospitalists’ duties to themselves and to their families are both intrinsically and instrumentally important. Being a hospitalist is not every hospitalist’s sole or predominant identity. They may also be adult children, spouses, and/or parents, or school board members or leaders in religious communities. Each of these roles entails its own duties and fulfilling them is also important. Effectuating them may, however, be more difficult because of the pandemic. Adult children may feel obligated to shop for their parents and parents of young children may have more childcare obligations. If no one else can fulfill these duties, they might take precedence over professional duties.

By fulfilling their duties to themselves and others, hospitalists may also be enabled to serve their patients. Unlike some discrete events, such as mass shootings or tornados, for which contingency and crisis standards of care may last for hours or days, we may be working under altered standards of care for weeks or months. (A contingency standard of care involves doing things differently in order to produce comparable clinical outcomes. A crisis standard of care is reached when it’s no longer possible to produce comparable clinical outcomes and the focus shifts from individual patient’s best interests or preferences to trying to save the most lives.³) It, therefore, is important we maintain our health and well-being by getting adequate sleep, eating well, and exercising.⁴ Arranging alternative child- and eldercare may reduce distractions at work and decrease the chance of needing to leave work unexpectedly.

In addressing these ethical issues, one of the key considerations is reducing the risks. We can reduce some risks ourselves while maintaining comparable outcomes to our conventional practices. I hope that it would go without saying, for example, that we should not work when we are sick. It is also important that we engage in adequate physical distancing whenever possible. It is important that physical distancing measures be applied equitably to all employees and that the actions hospitalists take to reduce their exposure do not disproportionately burden trainees or other types of providers. Consider, for example, having residents or nurse practitioners examine patients instead of the attending physician. This places subordinates at greater risk. Attending physicians, however, may have the best examination skills and their feedback is integral to trainees’ learning. Modeling a commitment to the duty to care and equitably accepting risk is exceptionally important as team members and leaders.

We can check in with one another and support each other emotionally. If some colleagues have substantially higher risks of complications, they may be assigned alternative duties with lower exposure risks. As a relatively young specialty, this may be more feasible for hospitalists than other specialties with a greater number of older practitioners. Care, however, should be taken to respect individuals’ privacy and confidentiality.

Minimizing risk is also a responsibility of hospitals and the local, state, and federal government. They have crucial roles in, for example, establishing adequate infection control policies and securing sufficient PPE. Many institutions have already moved to contingency standards of care to conserve PPE.⁵ These efforts not only support the duty of reciprocity⁶ but also help maintain an adequate workforce by reducing sick leave. The government’s apparent failure to fulfill its obligation to stockpile and distribute adequate equipment is currently being acutely felt.⁷

There are other potential actions that facilities can take, such as providing scrubs, child- and eldercare, housing, or life insurance. Individuals may be concerned about infecting family members. There is unfortunately limited data about spread on objects or asymptomatic spread, but these are reasonable possibilities. Facilities can provide scrubs to employees who do not normally wear them to provide a further barrier between the facility and the employees’ homes. They can provide child and elder care. It has been wonderful to see local community organizations and groups of medical students provide childcare for healthcare workers and other essential employees.⁸ Healthcare facilities could also consider providing temporary housing to staff with family members at high risk of complications. During the Ebola outbreak, some facilities provided supplemental disability and life insurance to staff who volunteered to put themselves at risk to help assure that their families would be provided for if the staff member unfortunately contracted the virus and became disabled or died.

Reciprocal duties to healthcare workers in a crisis standard of care are unresolved. Establishing ethically and clinically sound ventilator triage criteria is complex.^9,10 Some argue that healthcare providers should have some degree of priority. One argument is that if they recover, they can return to work and save more lives. (Having individuals who have recovered and are theoretically immune treat patients without PPE is one proposed conservation strategy.) It is, however, unclear whether individuals are likely to recover in enough time to return to work while we are still in a crisis standard of care. A different argument is that healthcare workers should be given priority because they accepted risk. This assumes they were infected at work and not in the community. While this argument has merit, it could be influenced by or perceived to be influenced by self-interest. Prioritizing healthcare workers for scarce resources requires substantial community support.¹¹

While providers have a duty to accept some risks, this duty is not unlimited. The mitigation strategies may be unsuccessful, and the risks substantial. One can think of analogies in other fields. Firefighters, for example, expose themselves to risk to save lives and to protect property. They are trained to take calculated risks, considering the likelihood and type of benefit and the degree of risk, but not to be reckless. They will take greater risk to save a life than property, and less risk if the victim is unlikely to survive. Their obligation to accept risk is not unlimited. They may justifiably choose not to enter a building, which is at significant, imminent risk of collapse, to protect property. The same is true for physicians. They are obligated to expose themselves to some risk, but not at a high likelihood of serious injury or death. At some point the duty to care for patients becomes supererogatory; fulfilling the duty is no longer required but becomes optional and doing so is heroic.¹² Some facilities, for example, will not perform cardiopulmonary resuscitation under a crisis standard of care due to the high risk of exposure and the low likelihood of success.¹³

Weighing potential benefits and risk is difficult. This difficulty is exacerbated by uncertainty. Some decisions would be easier, for example, if there was better evidence regarding asymptomatic spread. Finally, the subjectivity of some of these decisions raises concerns about unconscious bias or self-interest. It is therefore valuable to make some decisions collectively rather than individually. In particular, it is important to include those with adequate situation awareness. Conversely, once decisions are made, it is valuable to communicate both the decision and its rationale, and to be open to revising them based on feedback.

Given the fear and uncertainty generated by the pandemic, some individuals may be tempted to act unethically. Individuals have, unfortunately, taken hospital supplies, such as masks and hand sanitizer, for household use, and healthcare providers have hoarded medications, such as hydroxychloroquine.¹⁴ Individuals may also be tempted to use PPE for encounters when it is not indicated. We should address these fears and anxieties in other ways, such as discussing them with colleagues, chaplains, social workers, or employee assistance programs. If you observe coworkers acting in a manner that appears to be unethical, it is important to address their behavior while still giving them the benefit of the doubt. If you do not receive a satisfactory response, you should utilize the appropriate chain of command.

Most hospitalists are encountering situations that they have not previously experienced in their careers. These situations generate significant fear and anxiety. Many of these situations involve tensions between our duties to our patients and our duties to ourselves and to our families and friends. This tension is heightened for individuals who are older or have chronic health conditions or have family members who are. While healthcare providers have an obligation to accept some risks, this duty is not unlimited. Hospitals, healthcare systems, and governments have reciprocal obligations to keep providers safe. It is important to think creatively about ways to minimize risk. Due to uncertainty and self-interest, it may be better to make decisions collectively and transparently.

Previously I urged you to take a look at a clinical report from the American Academy of Pediatrics that makes an excellent case for the importance of physical activity in the physical and mental health of children. I suggested we should view with some skepticism the authors’ recommendation that we include a quantifiable assessment of physical activity as a vital sign in our EHRs because I found it an unrealistic goal for most busy clinicians.

I also promised to write again and address the authors’ recommendation that we learn how to write an exercise prescription. The authors representing the AAP’s Council on Sports Medicine and Fitness and Section on Obesity observed that many pediatricians feel they lack “the experience or training to guide their patients toward meeting physical activity recommendations.” This is in some part because few if any medical schools or training programs include how to write an exercise prescription in their curricula. Certainly I don’t recall anyone sitting me down and telling me how to prescribe exercise. But, I submit that writing a workable exercise prescription for most patients doesn’t require any special training. However, it does require some common sense and touch of creativity.

Writing any kind of prescription means that you first must know the patient for whom you are writing it. What are his or her capabilities? If the patient has some physical disabilities, you may need to involve a physical therapist or the patient’s specialists in developing the options. But in most cases, common sense will provide you with a place to start.

More important than knowing the patient’s capability is discovering what kind of things the patient and his or her family already find attractive. Convincing people, young or old, they should exercise because it is good for them is more than likely destined to fail. Most of us who enjoy being active have found that it makes us feel better. It is very likely that we developed that affinity by first doing something active that we found enjoyable. Finding that fun gateway into an active lifestyle is where it helps to be creative and to have the patience to suggest multiple options as interest levels fade. For the patient or family who seems to enjoy numerical goals, pedometers and smartwatch fitness trackers can be a hook, but in my experience these gadgets seldom result in a sustainable activity habit.

Does your community have the resources from which the family can choose an activity to fill your prescription? You should know enough about your community’s recreational opportunities and the family’s financial and temporal limitations so that the activity you have prescribed is achievable.

The bottom line is that you must be prepared for failure because most of your thoughtfully crafted prescriptions won’t be taken or even filled. The inertia that we have built into our societies is often too great for families to overcome. But don’t give up. Ask at every visit about activity. Make follow-up visits to discuss the progress or lack of progress to demonstrate that you still consider exercise a valuable and potent piece of the wellness package. And continue to discourage excess screen time.

If you are feeling frustrated by your lack of success writing exercise prescriptions, you may discover that you can be more effective by speaking out at school board and recreation department meetings. Armed with the research included in the AAP’s recent clinical report, you may find powerful allies in the community who share your passion for helping children become more active.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Previously I urged you to take a look at a clinical report from the American Academy of Pediatrics that makes an excellent case for the importance of physical activity in the physical and mental health of children. I suggested we should view with some skepticism the authors’ recommendation that we include a quantifiable assessment of physical activity as a vital sign in our EHRs because I found it an unrealistic goal for most busy clinicians.

I also promised to write again and address the authors’ recommendation that we learn how to write an exercise prescription. The authors representing the AAP’s Council on Sports Medicine and Fitness and Section on Obesity observed that many pediatricians feel they lack “the experience or training to guide their patients toward meeting physical activity recommendations.” This is in some part because few if any medical schools or training programs include how to write an exercise prescription in their curricula. Certainly I don’t recall anyone sitting me down and telling me how to prescribe exercise. But, I submit that writing a workable exercise prescription for most patients doesn’t require any special training. However, it does require some common sense and touch of creativity.

Writing any kind of prescription means that you first must know the patient for whom you are writing it. What are his or her capabilities? If the patient has some physical disabilities, you may need to involve a physical therapist or the patient’s specialists in developing the options. But in most cases, common sense will provide you with a place to start.

More important than knowing the patient’s capability is discovering what kind of things the patient and his or her family already find attractive. Convincing people, young or old, they should exercise because it is good for them is more than likely destined to fail. Most of us who enjoy being active have found that it makes us feel better. It is very likely that we developed that affinity by first doing something active that we found enjoyable. Finding that fun gateway into an active lifestyle is where it helps to be creative and to have the patience to suggest multiple options as interest levels fade. For the patient or family who seems to enjoy numerical goals, pedometers and smartwatch fitness trackers can be a hook, but in my experience these gadgets seldom result in a sustainable activity habit.

Does your community have the resources from which the family can choose an activity to fill your prescription? You should know enough about your community’s recreational opportunities and the family’s financial and temporal limitations so that the activity you have prescribed is achievable.

The bottom line is that you must be prepared for failure because most of your thoughtfully crafted prescriptions won’t be taken or even filled. The inertia that we have built into our societies is often too great for families to overcome. But don’t give up. Ask at every visit about activity. Make follow-up visits to discuss the progress or lack of progress to demonstrate that you still consider exercise a valuable and potent piece of the wellness package. And continue to discourage excess screen time.

If you are feeling frustrated by your lack of success writing exercise prescriptions, you may discover that you can be more effective by speaking out at school board and recreation department meetings. Armed with the research included in the AAP’s recent clinical report, you may find powerful allies in the community who share your passion for helping children become more active.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Previously I urged you to take a look at a clinical report from the American Academy of Pediatrics that makes an excellent case for the importance of physical activity in the physical and mental health of children. I suggested we should view with some skepticism the authors’ recommendation that we include a quantifiable assessment of physical activity as a vital sign in our EHRs because I found it an unrealistic goal for most busy clinicians.

I also promised to write again and address the authors’ recommendation that we learn how to write an exercise prescription. The authors representing the AAP’s Council on Sports Medicine and Fitness and Section on Obesity observed that many pediatricians feel they lack “the experience or training to guide their patients toward meeting physical activity recommendations.” This is in some part because few if any medical schools or training programs include how to write an exercise prescription in their curricula. Certainly I don’t recall anyone sitting me down and telling me how to prescribe exercise. But, I submit that writing a workable exercise prescription for most patients doesn’t require any special training. However, it does require some common sense and touch of creativity.

Writing any kind of prescription means that you first must know the patient for whom you are writing it. What are his or her capabilities? If the patient has some physical disabilities, you may need to involve a physical therapist or the patient’s specialists in developing the options. But in most cases, common sense will provide you with a place to start.

More important than knowing the patient’s capability is discovering what kind of things the patient and his or her family already find attractive. Convincing people, young or old, they should exercise because it is good for them is more than likely destined to fail. Most of us who enjoy being active have found that it makes us feel better. It is very likely that we developed that affinity by first doing something active that we found enjoyable. Finding that fun gateway into an active lifestyle is where it helps to be creative and to have the patience to suggest multiple options as interest levels fade. For the patient or family who seems to enjoy numerical goals, pedometers and smartwatch fitness trackers can be a hook, but in my experience these gadgets seldom result in a sustainable activity habit.

Does your community have the resources from which the family can choose an activity to fill your prescription? You should know enough about your community’s recreational opportunities and the family’s financial and temporal limitations so that the activity you have prescribed is achievable.

The bottom line is that you must be prepared for failure because most of your thoughtfully crafted prescriptions won’t be taken or even filled. The inertia that we have built into our societies is often too great for families to overcome. But don’t give up. Ask at every visit about activity. Make follow-up visits to discuss the progress or lack of progress to demonstrate that you still consider exercise a valuable and potent piece of the wellness package. And continue to discourage excess screen time.

If you are feeling frustrated by your lack of success writing exercise prescriptions, you may discover that you can be more effective by speaking out at school board and recreation department meetings. Armed with the research included in the AAP’s recent clinical report, you may find powerful allies in the community who share your passion for helping children become more active.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Patients with gynecologic malignancies who consumed only water for 24 hours before and 24 hours after each chemotherapy cycle had fewer dose delays and reductions compared with patients who didn’t fast, results of a small study showed.

The study included 23 women with ovarian, uterine, or cervical cancer, most of whom received platinum-based chemotherapy and taxanes. Fewer treatment modifications were required among the 11 patients randomized to a 24-hour water-only fast before and after each chemotherapy cycle than among the 12 patients randomized to standard care. Furthermore, there were no hospital admissions in the fasting group and two admissions in the control group, according to study author Courtney J. Riedinger, MD, of the University of Tennessee Medical Center in Knoxville.

She and her colleagues detailed the rationale and results of this study in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. Data have been updated from the abstract.
 

Rationale

“There’s a lot of new research and interest about nonpharmacologic interventions and lifestyle modifications to help patients cope with chemotherapy and even help with treatment, potentially,” Dr. Riedinger said in an interview.

“We decided to test water-only fasting because there’s not much data about the cell-fitness effects of fasting” on chemotherapy outcomes, she said.

Pre-chemotherapy fasting is based on the concept of differential stress resistance intended to protect normal cells but not cancer cells from the effects of chemotherapy. Fasting decreases levels of insulin-like growth factor 1, which leads healthy cells to enter a protective state by decreasing cell growth and proliferation. Cancer cells, in contrast, cannot enter the protective state, and are therefore more vulnerable than healthy, quiescent cells when exposed to drugs that target the cell cycle, Dr. Riedinger and colleagues noted.

The team cited two studies suggesting a benefit from fasting prior to chemotherapy. In the first study, mice that underwent 48-60 hours of short-term fasting were significantly less likely to die after exposure to a high dose of etoposide, compared with mice that did not fast before exposure (PNAS; 105[24]: 8215-822).

The second study showed that breast and ovarian cancer patients had improved quality of life scores and decreased fatigue when they fasted for 36 hours before and 24 hours after a chemotherapy cycle (BMC Cancer;18: article 476).
 

Study details

Dr. Riedinger and colleagues conducted a nonblinded, randomized trial of fasting in women, aged 34-73 years, who had gynecologic malignancies treated with a planned six cycles of chemotherapy. The patients were instructed to maintain a water-only fast for 24 hours before and 24 hours after each cycle. Controls did not fast.

Patient functional status and quality of life were investigated with the National Comprehensive Cancer Network–Functional Assessment of Cancer Therapy Ovarian Symptom Index (NCCN-FACT FOSI-18). Questionnaires were completed at each chemotherapy visit, and the records were reviewed to evaluate compliance, changes in treatment plan, and hospitalizations.

In all, 92% of chemotherapy cycles were completed with fasting as directed.

There were no significant differences in any of the study measures between patients who fasted and those who did not. However, this study was not powered to detect a difference, according to Dr. Riedinger.

Still, there were trends suggesting a benefit to fasting. Fasting patients had a higher mean change in NCCN-FACT FOSI-18 score compared with controls – increases of 5.11 and .22, respectively.

Five patients in the fasting group required changes to their treatment regimen, compared with eight patients in the control group. In addition, there were no hospital admissions in the fasting group and two admissions in the control group.

Patients tolerated the fast well without significant weight loss, and there were no grade 3 or 4 toxicities among patients who fasted.

The investigators are planning a larger study to further evaluate the effect of fasting on quality of life scores and treatment, and to evaluate the effects of fasting on hematologic toxicities. Future studies will focus on the optimal duration of fasting and the use of fasting-mimicking diets to allow for longer fasting periods, Dr. Riedinger said.

The study was internally funded. The authors reported no conflicts of interest.

SOURCE: Riedinger CJ et al. SGO 2020. Abstract 22.

Patients with gynecologic malignancies who consumed only water for 24 hours before and 24 hours after each chemotherapy cycle had fewer dose delays and reductions compared with patients who didn’t fast, results of a small study showed.

The study included 23 women with ovarian, uterine, or cervical cancer, most of whom received platinum-based chemotherapy and taxanes. Fewer treatment modifications were required among the 11 patients randomized to a 24-hour water-only fast before and after each chemotherapy cycle than among the 12 patients randomized to standard care. Furthermore, there were no hospital admissions in the fasting group and two admissions in the control group, according to study author Courtney J. Riedinger, MD, of the University of Tennessee Medical Center in Knoxville.

She and her colleagues detailed the rationale and results of this study in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. Data have been updated from the abstract.
 

Rationale

“There’s a lot of new research and interest about nonpharmacologic interventions and lifestyle modifications to help patients cope with chemotherapy and even help with treatment, potentially,” Dr. Riedinger said in an interview.

“We decided to test water-only fasting because there’s not much data about the cell-fitness effects of fasting” on chemotherapy outcomes, she said.

Pre-chemotherapy fasting is based on the concept of differential stress resistance intended to protect normal cells but not cancer cells from the effects of chemotherapy. Fasting decreases levels of insulin-like growth factor 1, which leads healthy cells to enter a protective state by decreasing cell growth and proliferation. Cancer cells, in contrast, cannot enter the protective state, and are therefore more vulnerable than healthy, quiescent cells when exposed to drugs that target the cell cycle, Dr. Riedinger and colleagues noted.

The team cited two studies suggesting a benefit from fasting prior to chemotherapy. In the first study, mice that underwent 48-60 hours of short-term fasting were significantly less likely to die after exposure to a high dose of etoposide, compared with mice that did not fast before exposure (PNAS; 105[24]: 8215-822).

The second study showed that breast and ovarian cancer patients had improved quality of life scores and decreased fatigue when they fasted for 36 hours before and 24 hours after a chemotherapy cycle (BMC Cancer;18: article 476).
 

Study details

Dr. Riedinger and colleagues conducted a nonblinded, randomized trial of fasting in women, aged 34-73 years, who had gynecologic malignancies treated with a planned six cycles of chemotherapy. The patients were instructed to maintain a water-only fast for 24 hours before and 24 hours after each cycle. Controls did not fast.

Patient functional status and quality of life were investigated with the National Comprehensive Cancer Network–Functional Assessment of Cancer Therapy Ovarian Symptom Index (NCCN-FACT FOSI-18). Questionnaires were completed at each chemotherapy visit, and the records were reviewed to evaluate compliance, changes in treatment plan, and hospitalizations.

In all, 92% of chemotherapy cycles were completed with fasting as directed.

There were no significant differences in any of the study measures between patients who fasted and those who did not. However, this study was not powered to detect a difference, according to Dr. Riedinger.

Still, there were trends suggesting a benefit to fasting. Fasting patients had a higher mean change in NCCN-FACT FOSI-18 score compared with controls – increases of 5.11 and .22, respectively.

Five patients in the fasting group required changes to their treatment regimen, compared with eight patients in the control group. In addition, there were no hospital admissions in the fasting group and two admissions in the control group.

Patients tolerated the fast well without significant weight loss, and there were no grade 3 or 4 toxicities among patients who fasted.

The investigators are planning a larger study to further evaluate the effect of fasting on quality of life scores and treatment, and to evaluate the effects of fasting on hematologic toxicities. Future studies will focus on the optimal duration of fasting and the use of fasting-mimicking diets to allow for longer fasting periods, Dr. Riedinger said.

The study was internally funded. The authors reported no conflicts of interest.

SOURCE: Riedinger CJ et al. SGO 2020. Abstract 22.

Patients with gynecologic malignancies who consumed only water for 24 hours before and 24 hours after each chemotherapy cycle had fewer dose delays and reductions compared with patients who didn’t fast, results of a small study showed.

The study included 23 women with ovarian, uterine, or cervical cancer, most of whom received platinum-based chemotherapy and taxanes. Fewer treatment modifications were required among the 11 patients randomized to a 24-hour water-only fast before and after each chemotherapy cycle than among the 12 patients randomized to standard care. Furthermore, there were no hospital admissions in the fasting group and two admissions in the control group, according to study author Courtney J. Riedinger, MD, of the University of Tennessee Medical Center in Knoxville.

She and her colleagues detailed the rationale and results of this study in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. Data have been updated from the abstract.
 

Rationale

“There’s a lot of new research and interest about nonpharmacologic interventions and lifestyle modifications to help patients cope with chemotherapy and even help with treatment, potentially,” Dr. Riedinger said in an interview.

“We decided to test water-only fasting because there’s not much data about the cell-fitness effects of fasting” on chemotherapy outcomes, she said.

Pre-chemotherapy fasting is based on the concept of differential stress resistance intended to protect normal cells but not cancer cells from the effects of chemotherapy. Fasting decreases levels of insulin-like growth factor 1, which leads healthy cells to enter a protective state by decreasing cell growth and proliferation. Cancer cells, in contrast, cannot enter the protective state, and are therefore more vulnerable than healthy, quiescent cells when exposed to drugs that target the cell cycle, Dr. Riedinger and colleagues noted.

The team cited two studies suggesting a benefit from fasting prior to chemotherapy. In the first study, mice that underwent 48-60 hours of short-term fasting were significantly less likely to die after exposure to a high dose of etoposide, compared with mice that did not fast before exposure (PNAS; 105[24]: 8215-822).

The second study showed that breast and ovarian cancer patients had improved quality of life scores and decreased fatigue when they fasted for 36 hours before and 24 hours after a chemotherapy cycle (BMC Cancer;18: article 476).
 

Study details

Dr. Riedinger and colleagues conducted a nonblinded, randomized trial of fasting in women, aged 34-73 years, who had gynecologic malignancies treated with a planned six cycles of chemotherapy. The patients were instructed to maintain a water-only fast for 24 hours before and 24 hours after each cycle. Controls did not fast.

Patient functional status and quality of life were investigated with the National Comprehensive Cancer Network–Functional Assessment of Cancer Therapy Ovarian Symptom Index (NCCN-FACT FOSI-18). Questionnaires were completed at each chemotherapy visit, and the records were reviewed to evaluate compliance, changes in treatment plan, and hospitalizations.

In all, 92% of chemotherapy cycles were completed with fasting as directed.

There were no significant differences in any of the study measures between patients who fasted and those who did not. However, this study was not powered to detect a difference, according to Dr. Riedinger.

Still, there were trends suggesting a benefit to fasting. Fasting patients had a higher mean change in NCCN-FACT FOSI-18 score compared with controls – increases of 5.11 and .22, respectively.

Five patients in the fasting group required changes to their treatment regimen, compared with eight patients in the control group. In addition, there were no hospital admissions in the fasting group and two admissions in the control group.

Patients tolerated the fast well without significant weight loss, and there were no grade 3 or 4 toxicities among patients who fasted.

The investigators are planning a larger study to further evaluate the effect of fasting on quality of life scores and treatment, and to evaluate the effects of fasting on hematologic toxicities. Future studies will focus on the optimal duration of fasting and the use of fasting-mimicking diets to allow for longer fasting periods, Dr. Riedinger said.

The study was internally funded. The authors reported no conflicts of interest.

SOURCE: Riedinger CJ et al. SGO 2020. Abstract 22.

Patients taking isotretinoin can use telemedicine to meet with their prescribing physicians instead of in-person visits, and female patients can use at-home pregnancy tests to comply with the requirements of the iPLEDGE program during the COVID-19 pandemic, according to an update program posted on the iPLEDGE website.

Obencem/Thinkstock

The program’s other requirements – the prescription window and two forms of birth control – remain unchanged.

The change follows recent guidance from the Department of Health & Human Services and the Food and Drug Administration regarding accommodations for medical care and drugs subject to Risk Evaluation and Mitigation Strategies (REMS) in the midst of a public health emergency that requires most people to remain in their homes except for essential services.

Allowing females to take at-home pregnancy tests and communicate the results to physician according to their preference is “a game changer for the middle of a pandemic, obviously,” Neil Goldberg, MD, a dermatologist in Westchester County, New York, said in an interview. “These are patients who don’t need to spend time outside just to get pregnancy tests done. It makes it a lot easier.”

Dr. Goldberg is frustrated, however, that the accommodations have not been more widely publicized; he discovered the change incidentally when speaking to an iPLEDGE program representative to request a waiver for a patient who had taken her pregnancy test too early. The program had denied a similar request for a 15-year-old patient of his the previous week, despite the patient being abstinent and having been in shelter-in-place for several weeks.

“The size of your notice [on the website] should be proportionate to how important it is,” Dr. Goldberg said, and the small red box on the site is easy to miss. By contrast, asking anyone to leave their homes to go to a lab for a pregnancy test in the midst of a global pandemic so they can continue their medication would be putting patients at risk, he added.

The iPLEDGE program is designed in part to ensure unplanned pregnancies do not occur in females while taking the teratogenic acne drug. But the rules are onerous and difficult even during normal times, pointed out Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center in New York City and past president of the American Acne and Rosacea Society.

Male patients taking isotretinoin must visit their physician every month to get a new no-refills prescription, but females must get a pregnancy test at a Clinical Laboratory Improvement Amendments–certified lab, which must then provide physical results to the prescribing physician. The doctor enters the negative pregnancy test and the two forms of birth control the patient is taking in the iPLEDGE program site.

Then the patient must take an online test at home to acknowledge they understand what it means to not get pregnant and enter the two forms of birth control they are using – which must match what the doctor enters – before the pharmacy can dispense the drug. The entire process must occur within 7 days or else the patient has to wait 19 days before starting the process over.

“We run a very tight schedule for girls. And every month, we would worry that something would interfere, a snow storm or something else, and that they wouldn’t be able to complete their objectives within the 7-day period,” Dr Baldwin said in an interview. “It was always difficult, and now with us not being able to see the patient and the patient not wanting to go to the lab, this became completely impossible.”

Until this change, some patients may not have been able to get their prescription for severe nodulocystic acne, which can cause physical and psychological scarring, and “postponing treatment increases the likelihood of scarring,” Dr. Baldwin pointed out.

Patients taking isotretinoin can use telemedicine to meet with their prescribing physicians instead of in-person visits, and female patients can use at-home pregnancy tests to comply with the requirements of the iPLEDGE program during the COVID-19 pandemic, according to an update program posted on the iPLEDGE website.

Obencem/Thinkstock

The program’s other requirements – the prescription window and two forms of birth control – remain unchanged.

The change follows recent guidance from the Department of Health & Human Services and the Food and Drug Administration regarding accommodations for medical care and drugs subject to Risk Evaluation and Mitigation Strategies (REMS) in the midst of a public health emergency that requires most people to remain in their homes except for essential services.

Allowing females to take at-home pregnancy tests and communicate the results to physician according to their preference is “a game changer for the middle of a pandemic, obviously,” Neil Goldberg, MD, a dermatologist in Westchester County, New York, said in an interview. “These are patients who don’t need to spend time outside just to get pregnancy tests done. It makes it a lot easier.”

Dr. Goldberg is frustrated, however, that the accommodations have not been more widely publicized; he discovered the change incidentally when speaking to an iPLEDGE program representative to request a waiver for a patient who had taken her pregnancy test too early. The program had denied a similar request for a 15-year-old patient of his the previous week, despite the patient being abstinent and having been in shelter-in-place for several weeks.

“The size of your notice [on the website] should be proportionate to how important it is,” Dr. Goldberg said, and the small red box on the site is easy to miss. By contrast, asking anyone to leave their homes to go to a lab for a pregnancy test in the midst of a global pandemic so they can continue their medication would be putting patients at risk, he added.

The iPLEDGE program is designed in part to ensure unplanned pregnancies do not occur in females while taking the teratogenic acne drug. But the rules are onerous and difficult even during normal times, pointed out Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center in New York City and past president of the American Acne and Rosacea Society.

Male patients taking isotretinoin must visit their physician every month to get a new no-refills prescription, but females must get a pregnancy test at a Clinical Laboratory Improvement Amendments–certified lab, which must then provide physical results to the prescribing physician. The doctor enters the negative pregnancy test and the two forms of birth control the patient is taking in the iPLEDGE program site.

Then the patient must take an online test at home to acknowledge they understand what it means to not get pregnant and enter the two forms of birth control they are using – which must match what the doctor enters – before the pharmacy can dispense the drug. The entire process must occur within 7 days or else the patient has to wait 19 days before starting the process over.

“We run a very tight schedule for girls. And every month, we would worry that something would interfere, a snow storm or something else, and that they wouldn’t be able to complete their objectives within the 7-day period,” Dr Baldwin said in an interview. “It was always difficult, and now with us not being able to see the patient and the patient not wanting to go to the lab, this became completely impossible.”

Until this change, some patients may not have been able to get their prescription for severe nodulocystic acne, which can cause physical and psychological scarring, and “postponing treatment increases the likelihood of scarring,” Dr. Baldwin pointed out.

Patients taking isotretinoin can use telemedicine to meet with their prescribing physicians instead of in-person visits, and female patients can use at-home pregnancy tests to comply with the requirements of the iPLEDGE program during the COVID-19 pandemic, according to an update program posted on the iPLEDGE website.

Obencem/Thinkstock

The program’s other requirements – the prescription window and two forms of birth control – remain unchanged.

The change follows recent guidance from the Department of Health & Human Services and the Food and Drug Administration regarding accommodations for medical care and drugs subject to Risk Evaluation and Mitigation Strategies (REMS) in the midst of a public health emergency that requires most people to remain in their homes except for essential services.

Allowing females to take at-home pregnancy tests and communicate the results to physician according to their preference is “a game changer for the middle of a pandemic, obviously,” Neil Goldberg, MD, a dermatologist in Westchester County, New York, said in an interview. “These are patients who don’t need to spend time outside just to get pregnancy tests done. It makes it a lot easier.”

Dr. Goldberg is frustrated, however, that the accommodations have not been more widely publicized; he discovered the change incidentally when speaking to an iPLEDGE program representative to request a waiver for a patient who had taken her pregnancy test too early. The program had denied a similar request for a 15-year-old patient of his the previous week, despite the patient being abstinent and having been in shelter-in-place for several weeks.

“The size of your notice [on the website] should be proportionate to how important it is,” Dr. Goldberg said, and the small red box on the site is easy to miss. By contrast, asking anyone to leave their homes to go to a lab for a pregnancy test in the midst of a global pandemic so they can continue their medication would be putting patients at risk, he added.

The iPLEDGE program is designed in part to ensure unplanned pregnancies do not occur in females while taking the teratogenic acne drug. But the rules are onerous and difficult even during normal times, pointed out Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center in New York City and past president of the American Acne and Rosacea Society.

Male patients taking isotretinoin must visit their physician every month to get a new no-refills prescription, but females must get a pregnancy test at a Clinical Laboratory Improvement Amendments–certified lab, which must then provide physical results to the prescribing physician. The doctor enters the negative pregnancy test and the two forms of birth control the patient is taking in the iPLEDGE program site.

Then the patient must take an online test at home to acknowledge they understand what it means to not get pregnant and enter the two forms of birth control they are using – which must match what the doctor enters – before the pharmacy can dispense the drug. The entire process must occur within 7 days or else the patient has to wait 19 days before starting the process over.

“We run a very tight schedule for girls. And every month, we would worry that something would interfere, a snow storm or something else, and that they wouldn’t be able to complete their objectives within the 7-day period,” Dr Baldwin said in an interview. “It was always difficult, and now with us not being able to see the patient and the patient not wanting to go to the lab, this became completely impossible.”

Until this change, some patients may not have been able to get their prescription for severe nodulocystic acne, which can cause physical and psychological scarring, and “postponing treatment increases the likelihood of scarring,” Dr. Baldwin pointed out.

Intravenous (IV) esketamine is as safe and effective as IV ketamine for patients with treatment-resistant depression, new research suggests.

“Our study was the first randomized clinical trial directly comparing ketamine and esketamine in treatment-resistant depression,” senior investigator Lucas C. Quarantini, MD, PhD, division of psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil, said in an interview.

The findings showed that esketamine was not inferior to ketamine in remission of depressive symptoms 24 hours after a single IV dose, and the two treatments had similar side effect profiles, Dr. Quarantini said.

Furthermore, “our results showed that only the number of treatment failures was an important factor for the remission of symptoms,” he added.

The findings were scheduled to be presented at the Anxiety and Depression Association of America (ADAA) Conference 2020, along with publication in the Journal of Affective Disorders (2020 Mar 1;264:527-34). However, the ADAA conference was canceled in the wake of the coronavirus pandemic.

More treatment options

The randomized, double-blind noninferiority trial compared IV racemic ketamine and esketamine, two formulations of the glutamate NMDA receptor modulator drug. It included 63 participants (61.9% women; mean age, 47 years) with treatment-resistant major depressive disorder, as determined by DSM-5 criteria.

Participants were enrolled between March 2017 and June 2018 and randomized to receive a single subanesthetic dose of racemic ketamine (0.5 mg/kg; n = 29) or esketamine (0.25 mg/kg; n = 34) for 40 minutes.

Results showed esketamine to be noninferior to ketamine as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS).

At 24 hours following infusion, 24.1% of the ketamine group versus 29.4% of the esketamine group showed remission of depression. The difference of just 5.3% confirmed noninferiority.

Although ketamine showed a tendency to have a longer-lasting antidepressant effect compared with esketamine, the difference did not reach statistical significance and should be evaluated in future studies, the investigators noted.

Both treatments were safe and well tolerated. Consistent with previous studies, the most frequent side effects were dissociative symptoms, including derealization, depersonalization, and cardiovascular changes, and increased blood pressure and heart rate, which occurred equally in both groups. There were no serious adverse events in either study group.

The investigators noted that most of the previous research examining antidepressant effects of ketamine has used the IV racemic type. The current findings are particularly important for situations in which ketamine or intranasal esketamine, which was recently approved by the Food and Drug Administration, are unavailable, Dr. Quarantini said.

“What our study adds to what has been previously published is that the only way to really analyze if two drugs are equivalent is to compare them in a head-to-head trial; and that was what we did,” he said.

“Our findings bring a greater basis for practitioners from locations where intravenous esketamine is more easily obtainable than ketamine to use it as an affordable option for treating depressive patients,” Dr. Quarantini added.

“Since this [lack of availability] is the scenario here in Brazil, and probably in many other countries, all patients from these locations will benefit from this finding,” he said. 

While further evaluating the study results to determine which clinical characteristics were predictive of remission of depressive symptoms, the researchers assessed several key factors. The median duration of disease progression was 12 months, median number of depressive episodes was five, and median number of therapeutic treatment failures was three.

The investigators also looked at the number of suicide attempts and degree of dissociative behavior.

Of these factors, the number of therapeutic failures was the only significant predictor of symptom remission, with an odds ratio of 1.46 for each prior therapeutic failure (95% CI, 1.08-1.99).

“To date, we have not found [other] studies with similar data,” Dr. Quarantini noted.

“Identifying remission predictors may contribute to selecting more suitable candidates for the intervention and result in more individualized and effective patient management,” the investigators wrote.

Consistent findings

Commenting on the findings, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Conn., noted that key study limitations include the small sample size and lack of a placebo group.

Nevertheless, “I think it is fair to say that it is unlikely that the treatments are markedly different in their effects on depression over 24 hours,” he said in an interview.

Dr. Sanacora, director of the Yale Depression Research Program, was not involved with the current research.

The findings are “consistent with what we can extrapolate from other clinical trials examining racemic ketamine and esketamine separately,” he said.

Dr. Sanacora noted that because esketamine has been previously shown to be a more potent anesthetic than arketamine, the other component of racemic ketamine, it is “the primary form of ketamine used as an anesthetic agent in several regions of the world with the idea that it may be more selective for the desired anesthetic effect.”

Even with its limitations, the study does offer some notable yet preliminary insights, he added.

“It is interesting to see varying degrees of numerical differences between the two treatments at different time points,” Dr. Sanacora said. In addition, “there may be some differing effects between the two treatments over time, but we really do not have enough data to say much of anything [about that] with confidence at this point.”

The study was supported by the Programa de Pesquisa para o SUS through Fundação de Amparo à Pesquisa do Estado da Bahia. Dr. Quarantini has reported receiving consulting fees from Allergan, Abbott, Janssen Pharmaceuticals, and Lundbeck, and research fees from Janssen Pharmaceuticals. The other study authors’ disclosures are listed in the published article. Dr. Sanacora has reported consulting and/or conducting research from several pharmaceutical companies. He also holds shares in BioHaven Pharmaceuticals and is coinventor on a patent called “Glutamate Agents in the Treatment of Mental Disorders.”

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

Intravenous (IV) esketamine is as safe and effective as IV ketamine for patients with treatment-resistant depression, new research suggests.

“Our study was the first randomized clinical trial directly comparing ketamine and esketamine in treatment-resistant depression,” senior investigator Lucas C. Quarantini, MD, PhD, division of psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil, said in an interview.

The findings showed that esketamine was not inferior to ketamine in remission of depressive symptoms 24 hours after a single IV dose, and the two treatments had similar side effect profiles, Dr. Quarantini said.

Furthermore, “our results showed that only the number of treatment failures was an important factor for the remission of symptoms,” he added.

The findings were scheduled to be presented at the Anxiety and Depression Association of America (ADAA) Conference 2020, along with publication in the Journal of Affective Disorders (2020 Mar 1;264:527-34). However, the ADAA conference was canceled in the wake of the coronavirus pandemic.

More treatment options

The randomized, double-blind noninferiority trial compared IV racemic ketamine and esketamine, two formulations of the glutamate NMDA receptor modulator drug. It included 63 participants (61.9% women; mean age, 47 years) with treatment-resistant major depressive disorder, as determined by DSM-5 criteria.

Participants were enrolled between March 2017 and June 2018 and randomized to receive a single subanesthetic dose of racemic ketamine (0.5 mg/kg; n = 29) or esketamine (0.25 mg/kg; n = 34) for 40 minutes.

Results showed esketamine to be noninferior to ketamine as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS).

At 24 hours following infusion, 24.1% of the ketamine group versus 29.4% of the esketamine group showed remission of depression. The difference of just 5.3% confirmed noninferiority.

Although ketamine showed a tendency to have a longer-lasting antidepressant effect compared with esketamine, the difference did not reach statistical significance and should be evaluated in future studies, the investigators noted.

Both treatments were safe and well tolerated. Consistent with previous studies, the most frequent side effects were dissociative symptoms, including derealization, depersonalization, and cardiovascular changes, and increased blood pressure and heart rate, which occurred equally in both groups. There were no serious adverse events in either study group.

The investigators noted that most of the previous research examining antidepressant effects of ketamine has used the IV racemic type. The current findings are particularly important for situations in which ketamine or intranasal esketamine, which was recently approved by the Food and Drug Administration, are unavailable, Dr. Quarantini said.

“What our study adds to what has been previously published is that the only way to really analyze if two drugs are equivalent is to compare them in a head-to-head trial; and that was what we did,” he said.

“Our findings bring a greater basis for practitioners from locations where intravenous esketamine is more easily obtainable than ketamine to use it as an affordable option for treating depressive patients,” Dr. Quarantini added.

“Since this [lack of availability] is the scenario here in Brazil, and probably in many other countries, all patients from these locations will benefit from this finding,” he said. 

While further evaluating the study results to determine which clinical characteristics were predictive of remission of depressive symptoms, the researchers assessed several key factors. The median duration of disease progression was 12 months, median number of depressive episodes was five, and median number of therapeutic treatment failures was three.

The investigators also looked at the number of suicide attempts and degree of dissociative behavior.

Of these factors, the number of therapeutic failures was the only significant predictor of symptom remission, with an odds ratio of 1.46 for each prior therapeutic failure (95% CI, 1.08-1.99).

“To date, we have not found [other] studies with similar data,” Dr. Quarantini noted.

“Identifying remission predictors may contribute to selecting more suitable candidates for the intervention and result in more individualized and effective patient management,” the investigators wrote.

Consistent findings

Commenting on the findings, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Conn., noted that key study limitations include the small sample size and lack of a placebo group.

Nevertheless, “I think it is fair to say that it is unlikely that the treatments are markedly different in their effects on depression over 24 hours,” he said in an interview.

Dr. Sanacora, director of the Yale Depression Research Program, was not involved with the current research.

The findings are “consistent with what we can extrapolate from other clinical trials examining racemic ketamine and esketamine separately,” he said.

Dr. Sanacora noted that because esketamine has been previously shown to be a more potent anesthetic than arketamine, the other component of racemic ketamine, it is “the primary form of ketamine used as an anesthetic agent in several regions of the world with the idea that it may be more selective for the desired anesthetic effect.”

Even with its limitations, the study does offer some notable yet preliminary insights, he added.

“It is interesting to see varying degrees of numerical differences between the two treatments at different time points,” Dr. Sanacora said. In addition, “there may be some differing effects between the two treatments over time, but we really do not have enough data to say much of anything [about that] with confidence at this point.”

The study was supported by the Programa de Pesquisa para o SUS through Fundação de Amparo à Pesquisa do Estado da Bahia. Dr. Quarantini has reported receiving consulting fees from Allergan, Abbott, Janssen Pharmaceuticals, and Lundbeck, and research fees from Janssen Pharmaceuticals. The other study authors’ disclosures are listed in the published article. Dr. Sanacora has reported consulting and/or conducting research from several pharmaceutical companies. He also holds shares in BioHaven Pharmaceuticals and is coinventor on a patent called “Glutamate Agents in the Treatment of Mental Disorders.”

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

Intravenous (IV) esketamine is as safe and effective as IV ketamine for patients with treatment-resistant depression, new research suggests.

“Our study was the first randomized clinical trial directly comparing ketamine and esketamine in treatment-resistant depression,” senior investigator Lucas C. Quarantini, MD, PhD, division of psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil, said in an interview.

The findings showed that esketamine was not inferior to ketamine in remission of depressive symptoms 24 hours after a single IV dose, and the two treatments had similar side effect profiles, Dr. Quarantini said.

Furthermore, “our results showed that only the number of treatment failures was an important factor for the remission of symptoms,” he added.

The findings were scheduled to be presented at the Anxiety and Depression Association of America (ADAA) Conference 2020, along with publication in the Journal of Affective Disorders (2020 Mar 1;264:527-34). However, the ADAA conference was canceled in the wake of the coronavirus pandemic.

More treatment options

The randomized, double-blind noninferiority trial compared IV racemic ketamine and esketamine, two formulations of the glutamate NMDA receptor modulator drug. It included 63 participants (61.9% women; mean age, 47 years) with treatment-resistant major depressive disorder, as determined by DSM-5 criteria.

Participants were enrolled between March 2017 and June 2018 and randomized to receive a single subanesthetic dose of racemic ketamine (0.5 mg/kg; n = 29) or esketamine (0.25 mg/kg; n = 34) for 40 minutes.

Results showed esketamine to be noninferior to ketamine as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS).

At 24 hours following infusion, 24.1% of the ketamine group versus 29.4% of the esketamine group showed remission of depression. The difference of just 5.3% confirmed noninferiority.

Although ketamine showed a tendency to have a longer-lasting antidepressant effect compared with esketamine, the difference did not reach statistical significance and should be evaluated in future studies, the investigators noted.

Both treatments were safe and well tolerated. Consistent with previous studies, the most frequent side effects were dissociative symptoms, including derealization, depersonalization, and cardiovascular changes, and increased blood pressure and heart rate, which occurred equally in both groups. There were no serious adverse events in either study group.

The investigators noted that most of the previous research examining antidepressant effects of ketamine has used the IV racemic type. The current findings are particularly important for situations in which ketamine or intranasal esketamine, which was recently approved by the Food and Drug Administration, are unavailable, Dr. Quarantini said.

“What our study adds to what has been previously published is that the only way to really analyze if two drugs are equivalent is to compare them in a head-to-head trial; and that was what we did,” he said.

“Our findings bring a greater basis for practitioners from locations where intravenous esketamine is more easily obtainable than ketamine to use it as an affordable option for treating depressive patients,” Dr. Quarantini added.

“Since this [lack of availability] is the scenario here in Brazil, and probably in many other countries, all patients from these locations will benefit from this finding,” he said. 

While further evaluating the study results to determine which clinical characteristics were predictive of remission of depressive symptoms, the researchers assessed several key factors. The median duration of disease progression was 12 months, median number of depressive episodes was five, and median number of therapeutic treatment failures was three.

The investigators also looked at the number of suicide attempts and degree of dissociative behavior.

Of these factors, the number of therapeutic failures was the only significant predictor of symptom remission, with an odds ratio of 1.46 for each prior therapeutic failure (95% CI, 1.08-1.99).

“To date, we have not found [other] studies with similar data,” Dr. Quarantini noted.

“Identifying remission predictors may contribute to selecting more suitable candidates for the intervention and result in more individualized and effective patient management,” the investigators wrote.

Consistent findings

Commenting on the findings, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University, New Haven, Conn., noted that key study limitations include the small sample size and lack of a placebo group.

Nevertheless, “I think it is fair to say that it is unlikely that the treatments are markedly different in their effects on depression over 24 hours,” he said in an interview.

Dr. Sanacora, director of the Yale Depression Research Program, was not involved with the current research.

The findings are “consistent with what we can extrapolate from other clinical trials examining racemic ketamine and esketamine separately,” he said.

Dr. Sanacora noted that because esketamine has been previously shown to be a more potent anesthetic than arketamine, the other component of racemic ketamine, it is “the primary form of ketamine used as an anesthetic agent in several regions of the world with the idea that it may be more selective for the desired anesthetic effect.”

Even with its limitations, the study does offer some notable yet preliminary insights, he added.

“It is interesting to see varying degrees of numerical differences between the two treatments at different time points,” Dr. Sanacora said. In addition, “there may be some differing effects between the two treatments over time, but we really do not have enough data to say much of anything [about that] with confidence at this point.”

The study was supported by the Programa de Pesquisa para o SUS through Fundação de Amparo à Pesquisa do Estado da Bahia. Dr. Quarantini has reported receiving consulting fees from Allergan, Abbott, Janssen Pharmaceuticals, and Lundbeck, and research fees from Janssen Pharmaceuticals. The other study authors’ disclosures are listed in the published article. Dr. Sanacora has reported consulting and/or conducting research from several pharmaceutical companies. He also holds shares in BioHaven Pharmaceuticals and is coinventor on a patent called “Glutamate Agents in the Treatment of Mental Disorders.”

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

Characteristics of patients with chronic lymphocytic leukemia can mask COVID-19 infection, creating a risk for patients, practitioners, and the community, according to a case study published in the Lancet Haematology.

Courtesy NIAID-RML

A 39-year-old man with a history of non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL) presented at a clinic in Wenzhou, China, with symptoms of fever, sore throat, productive cough, and dyspnea, according to the authors. COVID-19 infection was not initially suspected, as his whole blood cell and lymphocyte counts were high, the CLL masked a potential infection, and the patient claimed he had no suspect recent travel history.

However, a CT chest scan showed bilateral ground-glass opacities and a small amount of fluid in the patient’s left pleural cavity, leading the attending physician to suspect COVID-19. Testing was ordered and the real-time reverse-transcription polymerase chain reaction assay result was positive. The patient was immediately transferred to the isolation ward for management and confirmed COVID-19 infection.

Subsequently, the patient admitted travel to the COVID-19 epicenter in Wuhan province, although it was 25 days prior, indicating a longer period of incubation than generally believed, according to the authors. The patient survived treatment and was eventually discharged.

“Clinical and biochemical data of COVID-19 might be partly masked by coexisting chronic lymphocytic leukemia; better diagnostic strategies (i.e., superior CT differential techniques such as radiomics) could be used for diagnosis,” the researchers concluded, speculating that the apparently longer-than-normal COVID-19 incubation period might be the result of the patient’s compromised immune system.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jin X-H et al. Lancet Haematol. 2020;7(4):E351-2.

Characteristics of patients with chronic lymphocytic leukemia can mask COVID-19 infection, creating a risk for patients, practitioners, and the community, according to a case study published in the Lancet Haematology.

Courtesy NIAID-RML

A 39-year-old man with a history of non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL) presented at a clinic in Wenzhou, China, with symptoms of fever, sore throat, productive cough, and dyspnea, according to the authors. COVID-19 infection was not initially suspected, as his whole blood cell and lymphocyte counts were high, the CLL masked a potential infection, and the patient claimed he had no suspect recent travel history.

However, a CT chest scan showed bilateral ground-glass opacities and a small amount of fluid in the patient’s left pleural cavity, leading the attending physician to suspect COVID-19. Testing was ordered and the real-time reverse-transcription polymerase chain reaction assay result was positive. The patient was immediately transferred to the isolation ward for management and confirmed COVID-19 infection.

Subsequently, the patient admitted travel to the COVID-19 epicenter in Wuhan province, although it was 25 days prior, indicating a longer period of incubation than generally believed, according to the authors. The patient survived treatment and was eventually discharged.

“Clinical and biochemical data of COVID-19 might be partly masked by coexisting chronic lymphocytic leukemia; better diagnostic strategies (i.e., superior CT differential techniques such as radiomics) could be used for diagnosis,” the researchers concluded, speculating that the apparently longer-than-normal COVID-19 incubation period might be the result of the patient’s compromised immune system.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jin X-H et al. Lancet Haematol. 2020;7(4):E351-2.

Characteristics of patients with chronic lymphocytic leukemia can mask COVID-19 infection, creating a risk for patients, practitioners, and the community, according to a case study published in the Lancet Haematology.

Courtesy NIAID-RML

A 39-year-old man with a history of non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL) presented at a clinic in Wenzhou, China, with symptoms of fever, sore throat, productive cough, and dyspnea, according to the authors. COVID-19 infection was not initially suspected, as his whole blood cell and lymphocyte counts were high, the CLL masked a potential infection, and the patient claimed he had no suspect recent travel history.

However, a CT chest scan showed bilateral ground-glass opacities and a small amount of fluid in the patient’s left pleural cavity, leading the attending physician to suspect COVID-19. Testing was ordered and the real-time reverse-transcription polymerase chain reaction assay result was positive. The patient was immediately transferred to the isolation ward for management and confirmed COVID-19 infection.

Subsequently, the patient admitted travel to the COVID-19 epicenter in Wuhan province, although it was 25 days prior, indicating a longer period of incubation than generally believed, according to the authors. The patient survived treatment and was eventually discharged.

“Clinical and biochemical data of COVID-19 might be partly masked by coexisting chronic lymphocytic leukemia; better diagnostic strategies (i.e., superior CT differential techniques such as radiomics) could be used for diagnosis,” the researchers concluded, speculating that the apparently longer-than-normal COVID-19 incubation period might be the result of the patient’s compromised immune system.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jin X-H et al. Lancet Haematol. 2020;7(4):E351-2.

Skin manifestations were observed in about one-fifth of a group of patients with COVID-19 in the Alessandro Manzoni Hospital in Lecco, in northern Italy.

Courtesy of Dr. Randy Jacobs

Dermatologists there were pulled from their usual duty to help with the pandemic and looked at what was going on with the skin in 148 COVID-19 inpatients. They excluded 60 who had started new drugs within 15 days to rule out acute drug reactions, then reported what they saw (J Eur Acad Dermatol Venereol. 2020 Mar 26. doi: 10.1111/jdv.16387).

Of the 88 COVID-19 patients, 20.5% developed skin manifestations. Eight of the 18 (44%) had skin eruptions at symptom onset, and the rest after hospitalization. Fourteen (78%) had red rashes, three had widespread urticaria, and one had chickenpox-like vesicles. The most commonly affected area was the trunk. Itching was mild or absent, and lesions usually healed up in a few days. Most importantly, skin manifestations did not correlate with disease severity.

These skin manifestations “are similar to cutaneous involvement occurring during common viral infections,” said the author of the report, Sebastiano Recalcati, MD, a dermatologist at Alessandro Manzoni Hospital.

COVID-19 skin manifestations can cloud the diagnosis, according to the authors of another report from Thailand, where the first case of COVID-19 outside of China was reported.

They described a case of a COVID-19 infection in a Bangkok hospital that masqueraded as dengue fever. A person there presented with only a skin rash, petechiae, and a low platelet count, and was diagnosed with Dengue because that’s exactly what it looked like, the authors wrote (J Am Acad Dermatol. 2020 Mar 22. pii: S0190-9622[20]30454-0. doi: 10.1016/j.jaad.2020.03.036).

The correct diagnosis, COVID-19, was made at a tertiary care center after the patient was admitted with respiratory problems.

“There is a possibility that a COVID-19 patient might initially present with a skin rash that can be misdiagnosed as another common disease. ... The practitioner should recognize the possibility that the patient might have only a skin rash” at first, said the lead author of that report, Beuy Joob, PhD, of the Sanitation1 Medical Academic Center, Bangkok, and a coauthor.

There are similar reports in the United States, too. “Many have wondered if COVID-19 presents with any particular skin changes. The answer is yes,” said Randy Jacobs, MD, an assistant clinical professor of dermatology at the University of California, Riverside, who also has a private practice in southern California.

“COVID-19 can feature signs of small blood vessel occlusion. These can be petechiae or tiny bruises, and transient livedoid eruptions,” he said in an interview.

Dr. Jacobs had a 67-year-old patient who presented with a low fever, nasal congestion, postnasal drip, and a wet cough but no shortness of breath. It looked like a common cold. But a week later, the man had a nonpruritic blanching livedoid vascular eruption on his right anterior thigh, and blood in his urine, and he felt weak. The vascular eruption and bloody urine resolved in 24 hours, but the COVID-19 test came back positive and his cough became dry and hacking, and the weakness persisted. He’s in a hospital now and on oxygen, but not ventilated so far.

“Another dermatologist friend of mine also reported a similar transient COVID-19 unilateral livedoid eruption,” Dr. Jacobs said.

It suggests vaso-occlusion. Whether it’s neurogenic, microthrombotic, or immune complex mediated is unknown, but it’s “a skin finding that can help clinicians as they work up their patients with COVID-19 symptoms,” he noted.

Dr. Jacobs and the authors of the studies had no disclosures.

[email protected]

Skin manifestations were observed in about one-fifth of a group of patients with COVID-19 in the Alessandro Manzoni Hospital in Lecco, in northern Italy.

Courtesy of Dr. Randy Jacobs

Dermatologists there were pulled from their usual duty to help with the pandemic and looked at what was going on with the skin in 148 COVID-19 inpatients. They excluded 60 who had started new drugs within 15 days to rule out acute drug reactions, then reported what they saw (J Eur Acad Dermatol Venereol. 2020 Mar 26. doi: 10.1111/jdv.16387).

Of the 88 COVID-19 patients, 20.5% developed skin manifestations. Eight of the 18 (44%) had skin eruptions at symptom onset, and the rest after hospitalization. Fourteen (78%) had red rashes, three had widespread urticaria, and one had chickenpox-like vesicles. The most commonly affected area was the trunk. Itching was mild or absent, and lesions usually healed up in a few days. Most importantly, skin manifestations did not correlate with disease severity.

These skin manifestations “are similar to cutaneous involvement occurring during common viral infections,” said the author of the report, Sebastiano Recalcati, MD, a dermatologist at Alessandro Manzoni Hospital.

COVID-19 skin manifestations can cloud the diagnosis, according to the authors of another report from Thailand, where the first case of COVID-19 outside of China was reported.

They described a case of a COVID-19 infection in a Bangkok hospital that masqueraded as dengue fever. A person there presented with only a skin rash, petechiae, and a low platelet count, and was diagnosed with Dengue because that’s exactly what it looked like, the authors wrote (J Am Acad Dermatol. 2020 Mar 22. pii: S0190-9622[20]30454-0. doi: 10.1016/j.jaad.2020.03.036).

The correct diagnosis, COVID-19, was made at a tertiary care center after the patient was admitted with respiratory problems.

“There is a possibility that a COVID-19 patient might initially present with a skin rash that can be misdiagnosed as another common disease. ... The practitioner should recognize the possibility that the patient might have only a skin rash” at first, said the lead author of that report, Beuy Joob, PhD, of the Sanitation1 Medical Academic Center, Bangkok, and a coauthor.

There are similar reports in the United States, too. “Many have wondered if COVID-19 presents with any particular skin changes. The answer is yes,” said Randy Jacobs, MD, an assistant clinical professor of dermatology at the University of California, Riverside, who also has a private practice in southern California.

“COVID-19 can feature signs of small blood vessel occlusion. These can be petechiae or tiny bruises, and transient livedoid eruptions,” he said in an interview.

Dr. Jacobs had a 67-year-old patient who presented with a low fever, nasal congestion, postnasal drip, and a wet cough but no shortness of breath. It looked like a common cold. But a week later, the man had a nonpruritic blanching livedoid vascular eruption on his right anterior thigh, and blood in his urine, and he felt weak. The vascular eruption and bloody urine resolved in 24 hours, but the COVID-19 test came back positive and his cough became dry and hacking, and the weakness persisted. He’s in a hospital now and on oxygen, but not ventilated so far.

“Another dermatologist friend of mine also reported a similar transient COVID-19 unilateral livedoid eruption,” Dr. Jacobs said.

It suggests vaso-occlusion. Whether it’s neurogenic, microthrombotic, or immune complex mediated is unknown, but it’s “a skin finding that can help clinicians as they work up their patients with COVID-19 symptoms,” he noted.

Dr. Jacobs and the authors of the studies had no disclosures.

[email protected]

Skin manifestations were observed in about one-fifth of a group of patients with COVID-19 in the Alessandro Manzoni Hospital in Lecco, in northern Italy.

Courtesy of Dr. Randy Jacobs

Dermatologists there were pulled from their usual duty to help with the pandemic and looked at what was going on with the skin in 148 COVID-19 inpatients. They excluded 60 who had started new drugs within 15 days to rule out acute drug reactions, then reported what they saw (J Eur Acad Dermatol Venereol. 2020 Mar 26. doi: 10.1111/jdv.16387).

Of the 88 COVID-19 patients, 20.5% developed skin manifestations. Eight of the 18 (44%) had skin eruptions at symptom onset, and the rest after hospitalization. Fourteen (78%) had red rashes, three had widespread urticaria, and one had chickenpox-like vesicles. The most commonly affected area was the trunk. Itching was mild or absent, and lesions usually healed up in a few days. Most importantly, skin manifestations did not correlate with disease severity.

These skin manifestations “are similar to cutaneous involvement occurring during common viral infections,” said the author of the report, Sebastiano Recalcati, MD, a dermatologist at Alessandro Manzoni Hospital.

COVID-19 skin manifestations can cloud the diagnosis, according to the authors of another report from Thailand, where the first case of COVID-19 outside of China was reported.

They described a case of a COVID-19 infection in a Bangkok hospital that masqueraded as dengue fever. A person there presented with only a skin rash, petechiae, and a low platelet count, and was diagnosed with Dengue because that’s exactly what it looked like, the authors wrote (J Am Acad Dermatol. 2020 Mar 22. pii: S0190-9622[20]30454-0. doi: 10.1016/j.jaad.2020.03.036).

The correct diagnosis, COVID-19, was made at a tertiary care center after the patient was admitted with respiratory problems.

“There is a possibility that a COVID-19 patient might initially present with a skin rash that can be misdiagnosed as another common disease. ... The practitioner should recognize the possibility that the patient might have only a skin rash” at first, said the lead author of that report, Beuy Joob, PhD, of the Sanitation1 Medical Academic Center, Bangkok, and a coauthor.

There are similar reports in the United States, too. “Many have wondered if COVID-19 presents with any particular skin changes. The answer is yes,” said Randy Jacobs, MD, an assistant clinical professor of dermatology at the University of California, Riverside, who also has a private practice in southern California.

“COVID-19 can feature signs of small blood vessel occlusion. These can be petechiae or tiny bruises, and transient livedoid eruptions,” he said in an interview.

Dr. Jacobs had a 67-year-old patient who presented with a low fever, nasal congestion, postnasal drip, and a wet cough but no shortness of breath. It looked like a common cold. But a week later, the man had a nonpruritic blanching livedoid vascular eruption on his right anterior thigh, and blood in his urine, and he felt weak. The vascular eruption and bloody urine resolved in 24 hours, but the COVID-19 test came back positive and his cough became dry and hacking, and the weakness persisted. He’s in a hospital now and on oxygen, but not ventilated so far.

“Another dermatologist friend of mine also reported a similar transient COVID-19 unilateral livedoid eruption,” Dr. Jacobs said.

It suggests vaso-occlusion. Whether it’s neurogenic, microthrombotic, or immune complex mediated is unknown, but it’s “a skin finding that can help clinicians as they work up their patients with COVID-19 symptoms,” he noted.

Dr. Jacobs and the authors of the studies had no disclosures.

[email protected]

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The experimental agent adavosertib showed hints of efficacy against recurrent uterine serous carcinoma in early data from a phase 2 trial.

The overall response rate among 21 patients with advanced uterine serous carcinoma treated with adavosertib monotherapy was 30%, and an additional patient had an unconfirmed response at the time of data cutoff, reported Joyce F. Liu, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues.

“These results were noteworthy for the preliminary response rate of 30% that was observed in the first cohort of patients on this study, especially as, on average, patients on this study had received three prior treatments for their cancer. For us, this was an exciting signal of activity, especially for a targeted therapy used by itself in this type of cancer,” Dr. Liu said in an interview.

Preliminary results of the phase 2 trial were published in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

Adavosertib is a small molecule that inhibits the Wee1 kinase, a “gatekeeper” of the G2-M cell cycle checkpoint that is highly expressed and active in several types of cancer.

“Molecular characterization of these cancers has demonstrated that they have frequent p53 mutations as well as significant alterations in oncogenes,” Dr. Liu said. “These characteristics mean that these are cancers that may both have significant dysregulation of their cell cycle combined with high levels of replication stress. We hypothesized that these cancers could therefore be particularly vulnerable to further dysregulation of the cell cycle, which can be mediated by a drug such as adavosertib, which interrupts regulation of the G2-M cell cycle checkpoint by inhibiting the protein Wee1.”
 

Study details

The study enrolled women with recurrent uterine serous carcinoma. Patients were eligible if any disease component was considered to be serous, except for carcinosarcomas. The patients had a minimum of one prior platinum-based chemotherapy regimen (median 3, range 1-7), with no upper limit on prior lines of therapy required for eligibility.

Patients with microsatellite high/deficient mismatch repair disease had to have received prior therapy with programmed death-1/ligand-1 inhibitor, or to have been deemed ineligible for immunotherapy with a checkpoint inhibitor.

The patients received adavosertib at 300 mg daily on days 1 through 5 and days 8 through 12 of each 21-day cycle.

The trial would be considered successful if at least of 4 of 35 patients planned for accrual had a confirmed response or if 8 patients were progression free at 6 months. The coprimary endpoints are overall response rate of 20% or more, or a progression-free survival rate at 6 months of 30% or more.
 

Results and next steps

As of Aug. 20, 2019, the investigators had enrolled 27 patients, of whom 21 were evaluable for response.

The overall response rate was 30%, consisting of six confirmed partial responses. One additional patient had an unconfirmed response. Eleven of the 21 patients had stable disease, and 3 had disease progression.

Eleven patients remained on treatment with adavosertib at the time of data cutoff. Progression-free survival data were not mature.

The most frequent adverse events included anemia and diarrhea in 67% of patients each, nausea in 58%, and fatigue in 50%.

Frequent grade 3 or higher adverse effects included anemia, neutropenia, and syncope, all occurring in 21% of patients.

Dr. Liu said the investigators plan to present updated data from the study at a future meeting.

“We are planning additional cohorts in this study that will allow us to more deeply investigate why certain uterine serous cancer patients had very good responses to adavosertib and to identify potential biomarkers of response,” she said.

“Additionally, we plan to investigate whether adavosertib has similar activity in another type of uterine cancer, uterine carcinosarcoma, that shares many similar molecular characteristics with uterine serous carcinoma, including p53 mutations and oncogenic alterations, that might make it similarly vulnerable to targeting Wee1,” she said.

Dr. Liu disclosed ties with AstraZeneca, which supported the trial, as well as Merck and other companies.

SOURCE: Liu JF et al. SGO 2020, Abstract 7.

The experimental agent adavosertib showed hints of efficacy against recurrent uterine serous carcinoma in early data from a phase 2 trial.

The overall response rate among 21 patients with advanced uterine serous carcinoma treated with adavosertib monotherapy was 30%, and an additional patient had an unconfirmed response at the time of data cutoff, reported Joyce F. Liu, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues.

“These results were noteworthy for the preliminary response rate of 30% that was observed in the first cohort of patients on this study, especially as, on average, patients on this study had received three prior treatments for their cancer. For us, this was an exciting signal of activity, especially for a targeted therapy used by itself in this type of cancer,” Dr. Liu said in an interview.

Preliminary results of the phase 2 trial were published in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

Adavosertib is a small molecule that inhibits the Wee1 kinase, a “gatekeeper” of the G2-M cell cycle checkpoint that is highly expressed and active in several types of cancer.

“Molecular characterization of these cancers has demonstrated that they have frequent p53 mutations as well as significant alterations in oncogenes,” Dr. Liu said. “These characteristics mean that these are cancers that may both have significant dysregulation of their cell cycle combined with high levels of replication stress. We hypothesized that these cancers could therefore be particularly vulnerable to further dysregulation of the cell cycle, which can be mediated by a drug such as adavosertib, which interrupts regulation of the G2-M cell cycle checkpoint by inhibiting the protein Wee1.”
 

Study details

The study enrolled women with recurrent uterine serous carcinoma. Patients were eligible if any disease component was considered to be serous, except for carcinosarcomas. The patients had a minimum of one prior platinum-based chemotherapy regimen (median 3, range 1-7), with no upper limit on prior lines of therapy required for eligibility.

Patients with microsatellite high/deficient mismatch repair disease had to have received prior therapy with programmed death-1/ligand-1 inhibitor, or to have been deemed ineligible for immunotherapy with a checkpoint inhibitor.

The patients received adavosertib at 300 mg daily on days 1 through 5 and days 8 through 12 of each 21-day cycle.

The trial would be considered successful if at least of 4 of 35 patients planned for accrual had a confirmed response or if 8 patients were progression free at 6 months. The coprimary endpoints are overall response rate of 20% or more, or a progression-free survival rate at 6 months of 30% or more.
 

Results and next steps

As of Aug. 20, 2019, the investigators had enrolled 27 patients, of whom 21 were evaluable for response.

The overall response rate was 30%, consisting of six confirmed partial responses. One additional patient had an unconfirmed response. Eleven of the 21 patients had stable disease, and 3 had disease progression.

Eleven patients remained on treatment with adavosertib at the time of data cutoff. Progression-free survival data were not mature.

The most frequent adverse events included anemia and diarrhea in 67% of patients each, nausea in 58%, and fatigue in 50%.

Frequent grade 3 or higher adverse effects included anemia, neutropenia, and syncope, all occurring in 21% of patients.

Dr. Liu said the investigators plan to present updated data from the study at a future meeting.

“We are planning additional cohorts in this study that will allow us to more deeply investigate why certain uterine serous cancer patients had very good responses to adavosertib and to identify potential biomarkers of response,” she said.

“Additionally, we plan to investigate whether adavosertib has similar activity in another type of uterine cancer, uterine carcinosarcoma, that shares many similar molecular characteristics with uterine serous carcinoma, including p53 mutations and oncogenic alterations, that might make it similarly vulnerable to targeting Wee1,” she said.

Dr. Liu disclosed ties with AstraZeneca, which supported the trial, as well as Merck and other companies.

SOURCE: Liu JF et al. SGO 2020, Abstract 7.

The experimental agent adavosertib showed hints of efficacy against recurrent uterine serous carcinoma in early data from a phase 2 trial.

The overall response rate among 21 patients with advanced uterine serous carcinoma treated with adavosertib monotherapy was 30%, and an additional patient had an unconfirmed response at the time of data cutoff, reported Joyce F. Liu, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues.

“These results were noteworthy for the preliminary response rate of 30% that was observed in the first cohort of patients on this study, especially as, on average, patients on this study had received three prior treatments for their cancer. For us, this was an exciting signal of activity, especially for a targeted therapy used by itself in this type of cancer,” Dr. Liu said in an interview.

Preliminary results of the phase 2 trial were published in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

Adavosertib is a small molecule that inhibits the Wee1 kinase, a “gatekeeper” of the G2-M cell cycle checkpoint that is highly expressed and active in several types of cancer.

“Molecular characterization of these cancers has demonstrated that they have frequent p53 mutations as well as significant alterations in oncogenes,” Dr. Liu said. “These characteristics mean that these are cancers that may both have significant dysregulation of their cell cycle combined with high levels of replication stress. We hypothesized that these cancers could therefore be particularly vulnerable to further dysregulation of the cell cycle, which can be mediated by a drug such as adavosertib, which interrupts regulation of the G2-M cell cycle checkpoint by inhibiting the protein Wee1.”
 

Study details

The study enrolled women with recurrent uterine serous carcinoma. Patients were eligible if any disease component was considered to be serous, except for carcinosarcomas. The patients had a minimum of one prior platinum-based chemotherapy regimen (median 3, range 1-7), with no upper limit on prior lines of therapy required for eligibility.

Patients with microsatellite high/deficient mismatch repair disease had to have received prior therapy with programmed death-1/ligand-1 inhibitor, or to have been deemed ineligible for immunotherapy with a checkpoint inhibitor.

The patients received adavosertib at 300 mg daily on days 1 through 5 and days 8 through 12 of each 21-day cycle.

The trial would be considered successful if at least of 4 of 35 patients planned for accrual had a confirmed response or if 8 patients were progression free at 6 months. The coprimary endpoints are overall response rate of 20% or more, or a progression-free survival rate at 6 months of 30% or more.
 

Results and next steps

As of Aug. 20, 2019, the investigators had enrolled 27 patients, of whom 21 were evaluable for response.

The overall response rate was 30%, consisting of six confirmed partial responses. One additional patient had an unconfirmed response. Eleven of the 21 patients had stable disease, and 3 had disease progression.

Eleven patients remained on treatment with adavosertib at the time of data cutoff. Progression-free survival data were not mature.

The most frequent adverse events included anemia and diarrhea in 67% of patients each, nausea in 58%, and fatigue in 50%.

Frequent grade 3 or higher adverse effects included anemia, neutropenia, and syncope, all occurring in 21% of patients.

Dr. Liu said the investigators plan to present updated data from the study at a future meeting.

“We are planning additional cohorts in this study that will allow us to more deeply investigate why certain uterine serous cancer patients had very good responses to adavosertib and to identify potential biomarkers of response,” she said.

“Additionally, we plan to investigate whether adavosertib has similar activity in another type of uterine cancer, uterine carcinosarcoma, that shares many similar molecular characteristics with uterine serous carcinoma, including p53 mutations and oncogenic alterations, that might make it similarly vulnerable to targeting Wee1,” she said.

Dr. Liu disclosed ties with AstraZeneca, which supported the trial, as well as Merck and other companies.

SOURCE: Liu JF et al. SGO 2020, Abstract 7.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.