In recent years, there has been increased scrutiny of transitions of care in medicine, particularly at hospital discharge. Much focus has been on preventing readmissions, motivated at least in part by the Affordable Care Act’s Hospital Readmissions Reduction Program, which financially penalizes hospitals for higher-than-expected readmission rates.¹ However, the problem of transition from hospital to home is not just a readmissions issue—it is a quality and patient safety issue.² Therefore, measuring readmissions alone is inadequate. More effective systems for transition from hospital to home are needed in order to deliver high-quality care that actually restores patient well-being after hospitalization.

In this month’s issue of Journal of Hospital Medicine, Schnipper and Samal, et al report the results of a stepped-wedge randomized trial examining the effect of a multifaceted intervention on postdischarge patient-centered outcomes when compared with usual care.³ At 30 days after discharge, adverse events were reduced from 23 per 100 patients in the usual care group to 18 per 100 patients in the intervention group, with an incidence rate ratio of 0.55 (95% CI, 0.35-0.84) after adjustment for study month and baseline characteristics. Interestingly, there was no statistically significant difference in nonelective readmissions, and penetrance was notably poor: The majority of components of the intervention were received by fewer than half of intended patients, and 13% failed to receive any component at all.

With such incomplete implementation, what explains the reduction in adverse events? To best answer this, it is helpful to recognize the transition from hospital to home as a complex problem rather than a complicated one.⁴ The difference is key. Complicated problems follow a predictable set of rules that can be thought of and planned for, and when the plan is methodically followed, complicated problems can be solved. Complex problems, on the other hand, have a more unpredictable interplay between multiple nonindependent and sometimes unknown factors. Complex problems cannot be solved by merely following a well-designed plan; rather, they require tremendous preparation, adaptability, and active management as the problem plays itself out.

Fortunately, Schnipper and Samal, et al properly identified the problem of transition from hospital to home as complex and approached it from a complexity mindset. In their design of a multifaceted intervention, they aimed high and cast a wide net. Understanding that different practices have different cultures and resources, they standardized the function of the intervention components rather than the exact form. As the trial progressed, they allowed for modification of the intervention, incorporating input from multiple stakeholders and feedback from early failures. Thus, by recognizing and embracing the complexity of the problem, the authors set themselves and their patients up for success. The most likely explanation for the observed effect of the intervention on this complex problem is therefore quite simple: The study design allowed for the components most likely to work to be most readily implemented on a patient-by-patient and practice-by-practice basis.

While the trial aims to imitate the “real world,” it does not leave clear-cut answers for real healthcare professionals. Without knowing if any individual component of the intervention was effective on its own, it may be difficult for institutions to justify the cost of implementation. And while there should be adequate incentive to action for any intervention that improves how patients function or feel, without a reduction in readmissions, the financial downside may in some instances be prohibitive.

Despite these limitations, the path forward is clear. Institutions looking to implement a similar program now should approach the problem with a complexity mindset, even if their downstream interventions may differ. Researchers looking to design similar trials should focus on narrowing the scope of the intervention while maintaining a complexity mindset, which might help lead to more widespread implementation of evidence-based interventions in the future. In teaching us more about the approach to finding a solution than the solution itself, the present study marks an important next step in hospital to home transitions of care and transitions-of-care research.

In recent years, there has been increased scrutiny of transitions of care in medicine, particularly at hospital discharge. Much focus has been on preventing readmissions, motivated at least in part by the Affordable Care Act’s Hospital Readmissions Reduction Program, which financially penalizes hospitals for higher-than-expected readmission rates.¹ However, the problem of transition from hospital to home is not just a readmissions issue—it is a quality and patient safety issue.² Therefore, measuring readmissions alone is inadequate. More effective systems for transition from hospital to home are needed in order to deliver high-quality care that actually restores patient well-being after hospitalization.

In this month’s issue of Journal of Hospital Medicine, Schnipper and Samal, et al report the results of a stepped-wedge randomized trial examining the effect of a multifaceted intervention on postdischarge patient-centered outcomes when compared with usual care.³ At 30 days after discharge, adverse events were reduced from 23 per 100 patients in the usual care group to 18 per 100 patients in the intervention group, with an incidence rate ratio of 0.55 (95% CI, 0.35-0.84) after adjustment for study month and baseline characteristics. Interestingly, there was no statistically significant difference in nonelective readmissions, and penetrance was notably poor: The majority of components of the intervention were received by fewer than half of intended patients, and 13% failed to receive any component at all.

With such incomplete implementation, what explains the reduction in adverse events? To best answer this, it is helpful to recognize the transition from hospital to home as a complex problem rather than a complicated one.⁴ The difference is key. Complicated problems follow a predictable set of rules that can be thought of and planned for, and when the plan is methodically followed, complicated problems can be solved. Complex problems, on the other hand, have a more unpredictable interplay between multiple nonindependent and sometimes unknown factors. Complex problems cannot be solved by merely following a well-designed plan; rather, they require tremendous preparation, adaptability, and active management as the problem plays itself out.

Fortunately, Schnipper and Samal, et al properly identified the problem of transition from hospital to home as complex and approached it from a complexity mindset. In their design of a multifaceted intervention, they aimed high and cast a wide net. Understanding that different practices have different cultures and resources, they standardized the function of the intervention components rather than the exact form. As the trial progressed, they allowed for modification of the intervention, incorporating input from multiple stakeholders and feedback from early failures. Thus, by recognizing and embracing the complexity of the problem, the authors set themselves and their patients up for success. The most likely explanation for the observed effect of the intervention on this complex problem is therefore quite simple: The study design allowed for the components most likely to work to be most readily implemented on a patient-by-patient and practice-by-practice basis.

While the trial aims to imitate the “real world,” it does not leave clear-cut answers for real healthcare professionals. Without knowing if any individual component of the intervention was effective on its own, it may be difficult for institutions to justify the cost of implementation. And while there should be adequate incentive to action for any intervention that improves how patients function or feel, without a reduction in readmissions, the financial downside may in some instances be prohibitive.

Despite these limitations, the path forward is clear. Institutions looking to implement a similar program now should approach the problem with a complexity mindset, even if their downstream interventions may differ. Researchers looking to design similar trials should focus on narrowing the scope of the intervention while maintaining a complexity mindset, which might help lead to more widespread implementation of evidence-based interventions in the future. In teaching us more about the approach to finding a solution than the solution itself, the present study marks an important next step in hospital to home transitions of care and transitions-of-care research.

In recent years, there has been increased scrutiny of transitions of care in medicine, particularly at hospital discharge. Much focus has been on preventing readmissions, motivated at least in part by the Affordable Care Act’s Hospital Readmissions Reduction Program, which financially penalizes hospitals for higher-than-expected readmission rates.¹ However, the problem of transition from hospital to home is not just a readmissions issue—it is a quality and patient safety issue.² Therefore, measuring readmissions alone is inadequate. More effective systems for transition from hospital to home are needed in order to deliver high-quality care that actually restores patient well-being after hospitalization.

In this month’s issue of Journal of Hospital Medicine, Schnipper and Samal, et al report the results of a stepped-wedge randomized trial examining the effect of a multifaceted intervention on postdischarge patient-centered outcomes when compared with usual care.³ At 30 days after discharge, adverse events were reduced from 23 per 100 patients in the usual care group to 18 per 100 patients in the intervention group, with an incidence rate ratio of 0.55 (95% CI, 0.35-0.84) after adjustment for study month and baseline characteristics. Interestingly, there was no statistically significant difference in nonelective readmissions, and penetrance was notably poor: The majority of components of the intervention were received by fewer than half of intended patients, and 13% failed to receive any component at all.

With such incomplete implementation, what explains the reduction in adverse events? To best answer this, it is helpful to recognize the transition from hospital to home as a complex problem rather than a complicated one.⁴ The difference is key. Complicated problems follow a predictable set of rules that can be thought of and planned for, and when the plan is methodically followed, complicated problems can be solved. Complex problems, on the other hand, have a more unpredictable interplay between multiple nonindependent and sometimes unknown factors. Complex problems cannot be solved by merely following a well-designed plan; rather, they require tremendous preparation, adaptability, and active management as the problem plays itself out.

Fortunately, Schnipper and Samal, et al properly identified the problem of transition from hospital to home as complex and approached it from a complexity mindset. In their design of a multifaceted intervention, they aimed high and cast a wide net. Understanding that different practices have different cultures and resources, they standardized the function of the intervention components rather than the exact form. As the trial progressed, they allowed for modification of the intervention, incorporating input from multiple stakeholders and feedback from early failures. Thus, by recognizing and embracing the complexity of the problem, the authors set themselves and their patients up for success. The most likely explanation for the observed effect of the intervention on this complex problem is therefore quite simple: The study design allowed for the components most likely to work to be most readily implemented on a patient-by-patient and practice-by-practice basis.

While the trial aims to imitate the “real world,” it does not leave clear-cut answers for real healthcare professionals. Without knowing if any individual component of the intervention was effective on its own, it may be difficult for institutions to justify the cost of implementation. And while there should be adequate incentive to action for any intervention that improves how patients function or feel, without a reduction in readmissions, the financial downside may in some instances be prohibitive.

Despite these limitations, the path forward is clear. Institutions looking to implement a similar program now should approach the problem with a complexity mindset, even if their downstream interventions may differ. Researchers looking to design similar trials should focus on narrowing the scope of the intervention while maintaining a complexity mindset, which might help lead to more widespread implementation of evidence-based interventions in the future. In teaching us more about the approach to finding a solution than the solution itself, the present study marks an important next step in hospital to home transitions of care and transitions-of-care research.

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

Optical treatments for acne are emerging as promising alternatives to conventional treatments, a development that inspires clinician researchers such as Fernanda H. Sakamoto, MD, PhD.

“I love treating acne, because it can have a huge impact on our patients’ lives,” Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, said during a virtual course on laser and aesthetic skin therapy. “Acne is the most common disease in dermatology, affecting about 80% of our patients. Eleven percent of these patients have difficult-to-treat acne, and it is also the No. 1 cause of depression and suicide among teenagers and young adults. And, even though there’s no strong evidence that optical treatments work better than conventional acne treatments, people still spend a lot on those treatments: more than 220 million in 2019.”

Early results from a pilot study suggest that use of a novel laser system known as Accure in patients with mild to moderate acne resulted in an 80% reduction in acne lesions at 12 weeks. The laser prototype, which uses a 1,726 nm wavelength and is being developed by researchers at the Wellman Center for Photomedicine, features a built-in thermal camera in the handpiece that allows the user to monitor the skin’s temperature during treatment.

In initial pilot studies of the device, Dr. Sakamoto and colleagues observed consistent damage of the sebaceous glands, with no damage to the epidermis, surrounding dermis, or other follicular structures. “But because the contrast of absorption of lipids and water is not very high, we needed to create a laser with features that we have never seen before,” she said. “One of them is a robust cooling system. The second prototype features a built-in thermal camera within the handpiece that allows us to see the temperature while we’re treating the patient. It also has built-in software that would shut down the laser if the temperature is too high. “This is the first laser with some safety features that will give the user direct feedback while treating the patient,” she said, noting that its “unique cooling system and real-time monitoring ... makes it different from any of the lasers we see on the market right now.”

Dr. Sakamoto and colleagues (Emil Tanghetti, MD, in San Diego, Roy Geronemus, MD, in New York, and Joel L. Cohen, MD, in Colorado) are conducting a clinical trial of the device, to evaluate whether Accure can selectively target sebaceous glands. As of Oct. 23, 2020, the study enrolled more than 50 patients, who are followed at 4, 8, 12, and 24 weeks post treatment, she said.

To date, 16 patients have completed the study, and the researchers have observed an average lesion reduction of 80% at 12 weeks post treatment, after four treatment sessions. This amounted to more than 12,000 trigger pulls of the device, with no unexpected adverse events. Average visual analogue scale pain scores immediately after treatment have been 1.09 out of 10.

Histologic assessment of skin samples collected from the study participants have revealed selective damage of the sebaceous glands with a normal epidermis and surrounding dermis. “Because this laser is near infrared, it is not absorbed by melanin, making it possible for a safe treatment in darker skin tones,” Dr. Sakamoto said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine.

“We have shown that it is possible to create a selective laser for acne treatment at 1,726 nm. We have proven it mathematically as well as with histological samples,” she said. “Now we are moving on to a larger clinical trial for the FDA clearance.”

Another strategy being developed for acne treatment is to make nonselective lasers selective by adding gold microparticles into the hair follicle and sebaceous glands, to allow the lasers to be absorbed. In a study that used a free electron laser, Dr. Sakamoto and colleagues demonstrated that these microparticles can stay within the sebaceous glands for selective damage of the sebaceous glands. In a subsequent pilot clinical trial they showed that the addition of the gold microparticles followed by a diode laser treatment made it possible to reduce both inflammatory and noninflammatory lesions.

More recently, an open-label European study of acne treatment with light absorbing gold microparticles and optical pulses demonstrated that the treatment led to an 80%-90% reduction of inflammatory lesions at 12 weeks, with a reduction of Investigator’s Global Assessment scale from 2 to 4.

The Food and Drug Administration cleared the treatment, Sebacia Microparticles, for the treatment of mild to moderate acne in September of 2018, but according to Dr. Sakamoto, “the company has struggled, as they were only commercializing the device in California and Washington, DC.”

Photodynamic therapy (PDT) is also being studied as an acne treatment. “PDT uses a photosensitizer that needs to be activated by a light source,” she noted. “The combination of red light and aminolevulinic acid (ALA) or methyl ester ALA has been shown to damage the sebaceous glands”.

In a recent randomized controlled trial that compared PDT to adapalene gel plus oral doxycycline, PDT showed superiority. “Because PDT induces apoptosis of the sebaceous glands, it causes a lot of pain and side effects after treatment,” Dr. Sakamoto said. “However, it can clear 80%-90% of acne in 80%-90% of patients. But because of the side effects, PDT should be limited to those patients who cannot take conventional treatments.”

Dr. Sakamoto reported having received research funding and/or consulting fees from numerous device and pharmaceutical companies.

[email protected]

The early days of the coronavirus disease 2019 (COVID-19) pandemic were fraught with uncertainty as hospitalists struggled to develop standards of care for noncritically ill patients. Although data were available from intensive care units (ICUs) in Asia and Europe, it was unclear whether these findings applied to the acute but noncritically ill patients who would ultimately make up most coronavirus admissions. Which therapeutics could benefit these patients? Who needs continuous cardiopulmonary monitoring? And perhaps most importantly, which patients are at risk for clinical deterioration?

In this issue, Nemer et al begin to answer these questions using a retrospective analysis of 350 noncritically ill COVID-19 patients admitted to non-ICU care at Cleveland Clinic hospitals in Ohio and Florida between March 13 and May 1, 2020.¹ The primary outcome was a composite of three endpoints: increased respiratory support (high-flow nasal cannula, noninvasive positive pressure ventilation, or intubation), ICU transfer, or death. The primary outcome occurred in 18% of all patients and the risk was greatest among patients with high admission levels of C-reactive protein (CRP). This analysis found that while clinically significant arrhythmias occurred in 14% of patients, 90% of those were in patients with either known cardiac disease or an elevated admission troponin T level and in only one case (<1%) necessitated transition to a higher level of care. Overall mortality for COVID-19 patients initially admitted to non-ICU settings was 3%.

While several tests have been proposed as clinically relevant to coronavirus disease, those recommendations are based on studies performed on critically ill patients outside of the US and have focused on survival, not clinical deterioration.^2,3 In their cohort of noncritically ill patients in the US, Nemer et al found that not only is CRP associated with clinical worsening, but that increasing levels of CRP are associated with increasing risk of deterioration. Perhaps even more interesting was the finding that no patient with a normal CRP suffered the composite outcome, including death. The authors did not report levels of other laboratory tests that have been associated with severe coronavirus disease, such as platelets, fibrin degradation products, or prolonged prothrombin time/activated partial thromboplastin time. As many clinicians will note, CRP’s lack of specificity may be its Achilles heel, potentially lowering its prognostic value. Still, given its wide availability, low cost, and rapid turnaround, CRP could serve as a screening tool to risk stratify admitted coronavirus patients, while also providing reassurance when it is normal.

The results of this study could also impact use of hospital resources. The findings regarding the low risk of arrhythmias provide support for limiting the use of continuous cardiac monitoring in noncritically ill patients without previous histories of cardiac disease or elevated admission troponin levels. Patients with normal admission CRP levels could potentially be monitored safely with intermittent pulse oximetry. Continuous pulse oximetry and cardiac monitoring are already overused in many hospitals, and in the case of coronavirus the implications are even more significant given the importance of minimizing unnecessary healthcare worker exposures.

The vast majority (79% to 90%) of patients hospitalized for coronavirus will be cared for in non–ICU settings,^4,5 yet most research has thus far focused on ICU patients. Nemer et al provide much-needed information on how to care for the noncritically ill coronavirus patients whom hospitalists are most likely to treat. As a resurgence of infections is expected this winter, this work has the potential to help physicians identify not only those who have the highest probability of deteriorating, but also those who may not. In a world of limited resources, knowing which patient is unlikely to deteriorate may be just as important as recognizing which one is.

The early days of the coronavirus disease 2019 (COVID-19) pandemic were fraught with uncertainty as hospitalists struggled to develop standards of care for noncritically ill patients. Although data were available from intensive care units (ICUs) in Asia and Europe, it was unclear whether these findings applied to the acute but noncritically ill patients who would ultimately make up most coronavirus admissions. Which therapeutics could benefit these patients? Who needs continuous cardiopulmonary monitoring? And perhaps most importantly, which patients are at risk for clinical deterioration?

In this issue, Nemer et al begin to answer these questions using a retrospective analysis of 350 noncritically ill COVID-19 patients admitted to non-ICU care at Cleveland Clinic hospitals in Ohio and Florida between March 13 and May 1, 2020.¹ The primary outcome was a composite of three endpoints: increased respiratory support (high-flow nasal cannula, noninvasive positive pressure ventilation, or intubation), ICU transfer, or death. The primary outcome occurred in 18% of all patients and the risk was greatest among patients with high admission levels of C-reactive protein (CRP). This analysis found that while clinically significant arrhythmias occurred in 14% of patients, 90% of those were in patients with either known cardiac disease or an elevated admission troponin T level and in only one case (<1%) necessitated transition to a higher level of care. Overall mortality for COVID-19 patients initially admitted to non-ICU settings was 3%.

While several tests have been proposed as clinically relevant to coronavirus disease, those recommendations are based on studies performed on critically ill patients outside of the US and have focused on survival, not clinical deterioration.^2,3 In their cohort of noncritically ill patients in the US, Nemer et al found that not only is CRP associated with clinical worsening, but that increasing levels of CRP are associated with increasing risk of deterioration. Perhaps even more interesting was the finding that no patient with a normal CRP suffered the composite outcome, including death. The authors did not report levels of other laboratory tests that have been associated with severe coronavirus disease, such as platelets, fibrin degradation products, or prolonged prothrombin time/activated partial thromboplastin time. As many clinicians will note, CRP’s lack of specificity may be its Achilles heel, potentially lowering its prognostic value. Still, given its wide availability, low cost, and rapid turnaround, CRP could serve as a screening tool to risk stratify admitted coronavirus patients, while also providing reassurance when it is normal.

The results of this study could also impact use of hospital resources. The findings regarding the low risk of arrhythmias provide support for limiting the use of continuous cardiac monitoring in noncritically ill patients without previous histories of cardiac disease or elevated admission troponin levels. Patients with normal admission CRP levels could potentially be monitored safely with intermittent pulse oximetry. Continuous pulse oximetry and cardiac monitoring are already overused in many hospitals, and in the case of coronavirus the implications are even more significant given the importance of minimizing unnecessary healthcare worker exposures.

The vast majority (79% to 90%) of patients hospitalized for coronavirus will be cared for in non–ICU settings,^4,5 yet most research has thus far focused on ICU patients. Nemer et al provide much-needed information on how to care for the noncritically ill coronavirus patients whom hospitalists are most likely to treat. As a resurgence of infections is expected this winter, this work has the potential to help physicians identify not only those who have the highest probability of deteriorating, but also those who may not. In a world of limited resources, knowing which patient is unlikely to deteriorate may be just as important as recognizing which one is.

The early days of the coronavirus disease 2019 (COVID-19) pandemic were fraught with uncertainty as hospitalists struggled to develop standards of care for noncritically ill patients. Although data were available from intensive care units (ICUs) in Asia and Europe, it was unclear whether these findings applied to the acute but noncritically ill patients who would ultimately make up most coronavirus admissions. Which therapeutics could benefit these patients? Who needs continuous cardiopulmonary monitoring? And perhaps most importantly, which patients are at risk for clinical deterioration?

In this issue, Nemer et al begin to answer these questions using a retrospective analysis of 350 noncritically ill COVID-19 patients admitted to non-ICU care at Cleveland Clinic hospitals in Ohio and Florida between March 13 and May 1, 2020.¹ The primary outcome was a composite of three endpoints: increased respiratory support (high-flow nasal cannula, noninvasive positive pressure ventilation, or intubation), ICU transfer, or death. The primary outcome occurred in 18% of all patients and the risk was greatest among patients with high admission levels of C-reactive protein (CRP). This analysis found that while clinically significant arrhythmias occurred in 14% of patients, 90% of those were in patients with either known cardiac disease or an elevated admission troponin T level and in only one case (<1%) necessitated transition to a higher level of care. Overall mortality for COVID-19 patients initially admitted to non-ICU settings was 3%.

While several tests have been proposed as clinically relevant to coronavirus disease, those recommendations are based on studies performed on critically ill patients outside of the US and have focused on survival, not clinical deterioration.^2,3 In their cohort of noncritically ill patients in the US, Nemer et al found that not only is CRP associated with clinical worsening, but that increasing levels of CRP are associated with increasing risk of deterioration. Perhaps even more interesting was the finding that no patient with a normal CRP suffered the composite outcome, including death. The authors did not report levels of other laboratory tests that have been associated with severe coronavirus disease, such as platelets, fibrin degradation products, or prolonged prothrombin time/activated partial thromboplastin time. As many clinicians will note, CRP’s lack of specificity may be its Achilles heel, potentially lowering its prognostic value. Still, given its wide availability, low cost, and rapid turnaround, CRP could serve as a screening tool to risk stratify admitted coronavirus patients, while also providing reassurance when it is normal.

The results of this study could also impact use of hospital resources. The findings regarding the low risk of arrhythmias provide support for limiting the use of continuous cardiac monitoring in noncritically ill patients without previous histories of cardiac disease or elevated admission troponin levels. Patients with normal admission CRP levels could potentially be monitored safely with intermittent pulse oximetry. Continuous pulse oximetry and cardiac monitoring are already overused in many hospitals, and in the case of coronavirus the implications are even more significant given the importance of minimizing unnecessary healthcare worker exposures.

The vast majority (79% to 90%) of patients hospitalized for coronavirus will be cared for in non–ICU settings,^4,5 yet most research has thus far focused on ICU patients. Nemer et al provide much-needed information on how to care for the noncritically ill coronavirus patients whom hospitalists are most likely to treat. As a resurgence of infections is expected this winter, this work has the potential to help physicians identify not only those who have the highest probability of deteriorating, but also those who may not. In a world of limited resources, knowing which patient is unlikely to deteriorate may be just as important as recognizing which one is.

“Our goals can only be reached through the vehicle of a plan. There is no other route to success.”

—Pablo Picasso

Whether it be a research manuscript, quality improvement (QI) initiative, or educational curriculum, busy clinicians often struggle getting projects past the idea stage. Barriers to completion, such as a busy clinical schedule or lack of experience and mentorship, are well known. Importantly, these projects serve as “academic currency” used for promotion and advancement and also create generalizable knowledge, which can help others improve clinical practice or operational processes. Those who are successful in completing their academic project frequently follow a well-structured path. Consider the following principles to get your idea across the finish line:

Find a blueprint. Among most academic projects, whether a research paper, QI project or new curriculum, an underlying formula is commonly applied. Before starting, do your background research. Is there a paper or method that resembles your desired approach? Is there a question or concept that caught your eye? Using a blueprint from existing evidence allows you to identify important structures, phrases, and terms to inform your manuscript. Once you have identified the blueprint, define your project and approach.

Find a mentor. While career mentorship is important for professional growth, you first need a project mentor. Being a project mentor is a smaller ask for a more senior colleague than being a career mentor, and it’s a great way to test-drive a potential long-term working relationship. Moreover, the successful completion of one project can potentially lead to further opportunities, and perhaps even a long-term career mentor.

Take initiative. In business, there is a common adage: “Never bring a problem to your boss without a proposed solution in hand.”¹ In academics, consider: “Never show up with an idea without bringing a proposal.” By bringing a defined proposal to the conversation, your inquiry is more likely to get a response because (a) it is not a blind-ask and (b) it creates a foundation to build on. This is analogous to an early learner presenting their assessment and plan in the clinical setting; you don’t stop at the diagnosis (your idea) without having a plan for how you want to manage it.

Get an accountability partner. Publicly committing to a goal increases the probability of accomplishing your task by 65%, while having an accountability partner increases that by 95%.² An accountability partner serves as a coach to help you accomplish a task. This individual can be a colleague, spouse, or friend and is typically not a part of the project. By leveraging peer pressure, you increase the odds of successfully completing your project.

Carve out dedicated time. The entrepreneur and author Jim Rohn once said, “Discipline is the bridge between goals and accomplishments.”³ To complete a project, you have to make the time to do the work. While many believe that successful writers sit and write for hours on end, many famous writers only wrote for a few hours at a time—but they did so consistently.⁴ Create your routine by setting aside consistent, defined time to work on your project. To extract the most value, select a time of the day in which you work best (eg, early morning). Then, set a timer for 30 minutes and write—or work.

Because you are a busy clinician with constant demands on your time, having the skillset to reliably turn an idea into “academic currency” is a necessity. Having a plan and following these principles will help you earn that academic coin.

“Our goals can only be reached through the vehicle of a plan. There is no other route to success.”

—Pablo Picasso

Whether it be a research manuscript, quality improvement (QI) initiative, or educational curriculum, busy clinicians often struggle getting projects past the idea stage. Barriers to completion, such as a busy clinical schedule or lack of experience and mentorship, are well known. Importantly, these projects serve as “academic currency” used for promotion and advancement and also create generalizable knowledge, which can help others improve clinical practice or operational processes. Those who are successful in completing their academic project frequently follow a well-structured path. Consider the following principles to get your idea across the finish line:

Find a blueprint. Among most academic projects, whether a research paper, QI project or new curriculum, an underlying formula is commonly applied. Before starting, do your background research. Is there a paper or method that resembles your desired approach? Is there a question or concept that caught your eye? Using a blueprint from existing evidence allows you to identify important structures, phrases, and terms to inform your manuscript. Once you have identified the blueprint, define your project and approach.

Find a mentor. While career mentorship is important for professional growth, you first need a project mentor. Being a project mentor is a smaller ask for a more senior colleague than being a career mentor, and it’s a great way to test-drive a potential long-term working relationship. Moreover, the successful completion of one project can potentially lead to further opportunities, and perhaps even a long-term career mentor.

Take initiative. In business, there is a common adage: “Never bring a problem to your boss without a proposed solution in hand.”¹ In academics, consider: “Never show up with an idea without bringing a proposal.” By bringing a defined proposal to the conversation, your inquiry is more likely to get a response because (a) it is not a blind-ask and (b) it creates a foundation to build on. This is analogous to an early learner presenting their assessment and plan in the clinical setting; you don’t stop at the diagnosis (your idea) without having a plan for how you want to manage it.

Get an accountability partner. Publicly committing to a goal increases the probability of accomplishing your task by 65%, while having an accountability partner increases that by 95%.² An accountability partner serves as a coach to help you accomplish a task. This individual can be a colleague, spouse, or friend and is typically not a part of the project. By leveraging peer pressure, you increase the odds of successfully completing your project.

Carve out dedicated time. The entrepreneur and author Jim Rohn once said, “Discipline is the bridge between goals and accomplishments.”³ To complete a project, you have to make the time to do the work. While many believe that successful writers sit and write for hours on end, many famous writers only wrote for a few hours at a time—but they did so consistently.⁴ Create your routine by setting aside consistent, defined time to work on your project. To extract the most value, select a time of the day in which you work best (eg, early morning). Then, set a timer for 30 minutes and write—or work.

Because you are a busy clinician with constant demands on your time, having the skillset to reliably turn an idea into “academic currency” is a necessity. Having a plan and following these principles will help you earn that academic coin.

“Our goals can only be reached through the vehicle of a plan. There is no other route to success.”

—Pablo Picasso

Whether it be a research manuscript, quality improvement (QI) initiative, or educational curriculum, busy clinicians often struggle getting projects past the idea stage. Barriers to completion, such as a busy clinical schedule or lack of experience and mentorship, are well known. Importantly, these projects serve as “academic currency” used for promotion and advancement and also create generalizable knowledge, which can help others improve clinical practice or operational processes. Those who are successful in completing their academic project frequently follow a well-structured path. Consider the following principles to get your idea across the finish line:

Find a blueprint. Among most academic projects, whether a research paper, QI project or new curriculum, an underlying formula is commonly applied. Before starting, do your background research. Is there a paper or method that resembles your desired approach? Is there a question or concept that caught your eye? Using a blueprint from existing evidence allows you to identify important structures, phrases, and terms to inform your manuscript. Once you have identified the blueprint, define your project and approach.

Find a mentor. While career mentorship is important for professional growth, you first need a project mentor. Being a project mentor is a smaller ask for a more senior colleague than being a career mentor, and it’s a great way to test-drive a potential long-term working relationship. Moreover, the successful completion of one project can potentially lead to further opportunities, and perhaps even a long-term career mentor.

Take initiative. In business, there is a common adage: “Never bring a problem to your boss without a proposed solution in hand.”¹ In academics, consider: “Never show up with an idea without bringing a proposal.” By bringing a defined proposal to the conversation, your inquiry is more likely to get a response because (a) it is not a blind-ask and (b) it creates a foundation to build on. This is analogous to an early learner presenting their assessment and plan in the clinical setting; you don’t stop at the diagnosis (your idea) without having a plan for how you want to manage it.

Get an accountability partner. Publicly committing to a goal increases the probability of accomplishing your task by 65%, while having an accountability partner increases that by 95%.² An accountability partner serves as a coach to help you accomplish a task. This individual can be a colleague, spouse, or friend and is typically not a part of the project. By leveraging peer pressure, you increase the odds of successfully completing your project.

Carve out dedicated time. The entrepreneur and author Jim Rohn once said, “Discipline is the bridge between goals and accomplishments.”³ To complete a project, you have to make the time to do the work. While many believe that successful writers sit and write for hours on end, many famous writers only wrote for a few hours at a time—but they did so consistently.⁴ Create your routine by setting aside consistent, defined time to work on your project. To extract the most value, select a time of the day in which you work best (eg, early morning). Then, set a timer for 30 minutes and write—or work.

Because you are a busy clinician with constant demands on your time, having the skillset to reliably turn an idea into “academic currency” is a necessity. Having a plan and following these principles will help you earn that academic coin.

We enter the new year still in the midst of the coronavirus disease 2019 (COVID-19) pandemic and remain humbled by its impact. It is remarkable how much, and how little, has changed. Hospitalists in the early days of the COVID-19 pandemic were struggling. We were caring for patients who were suffering and dying from a new and mysterious disease. There weren’t enough tests (or, if there were tests, there weren’t swabs).¹ We were using protocols for managing respiratory failure that, we would learn later, may not have been the best for improving outcomes. Rumors of unproven therapies came from everywhere: our patients, our colleagues, and even the highest realms of the federal government. We also knew very little about how best to protect ourselves. In many cases, we did not have enough personal protective equipment (PPE). There were no face shields, or “zoom rounds,” or even awareness that we probably shouldn’t sit in the tiny conference room (maskless) discussing patients with the large team of doctors, nurses, respiratory therapists, and social workers.

Perhaps worst of all, we were haunted. We were alarmed by the large numbers of young patients who were ill, and our elderly patients, many of whom we knew and had cared for many times, had suddenly just stopped showing up.² In our free moments, we worried about them; maybe they were afraid to come to the hospital, maybe they were home sick with COVID-19, or maybe they had died alone. And children, initially thought to be spared the most serious consequences of COVID-19, started coming to the hospital with a rare but severe new COVID-19-associated complication, termed multisystem inflammatory syndrome in children (MIS-C). We had to learn to manage yet another manifestation of COVID-19, largely through trial and error.

And, of course, clinical care was only one of our many responsibilities. We were also busy hunting for ventilators, setting up makeshift medical wards and intensive care units, revamping medical education, and scouring the literature for any information to help guide patient care. We worried about getting sick ourselves and bringing the disease home to our families. Our impatience grew as day after day there was no (and still is no) coordinated federal response.

A glimmer of hope slowly emerged. Our colleagues designed and rapidly evaluated respiratory protocols and provided early evidence about the strategies (eg, proning) that were associated with improved outcomes.³ Researchers began to generate knowledge and move us beyond rumors regarding potential therapies. We cheered as our administrators concocted unusual strategies to remedy the PPE and testing shortages.⁴

At the Journal of Hospital Medicine, we were faced with another challenge: How would we describe the chaos and the challenges of being a physician during the COVID-19 era? How would we document the way our colleagues were rising to the challenge and identifying opportunities to rethink hospital care in the United States?

In April, we began to receive a deluge of personal essays from frontline physicians about their experiences with COVID-19. Generally, medical journals publish and disseminate original, high-impact research. Personal essays rarely fit this model. Given the unprecedented circumstances, however, we decided these essays could help chronicle an important moment in medical history. In our May 2020 issue, we published only these essays. We continue to publish them online almost daily.

Some of the essays described how the healthcare system—previously thought to be hyperspecialized, profit-driven, and resistant to change—pivoted within days, as hospitalist physicians trained other physicians to “unspecialize” and pediatricians began to care for adults in an otherwise overwhelmed hospital system.^5,6 Another essay focused on the need to trust that medical students who had graduated early would be able to function as physicians.⁷ And yet another essay expressed concern about the widespread use of unproven therapies in hospitalized patients. “Even in times of global pandemic, we need to consider potential harms and adverse consequences of novel treatments,’’ the physicians wrote. “Sometimes inaction is preferable to action.”⁸

Several essays reflected on the impact of the pandemic on healthcare disparities, suggesting that the pandemic had made (the well-known but often ignored) differences in health outcomes between White patients and racial minorities more obvious. Still another essay reflected on the intersection between structural racism, poor access to care, and interpersonal racism, describing the grief caused by losses of Black lives to both police violence and COVID-19.⁹

There also were personal stories of hardship and survival. One hospitalist physician with asthma described coughing as ``the new leprosy.”¹⁰ She wrote, “This is a particularly unpropitious time in history to be a Chinese-American doctor who can’t stop coughing.”

There were drawbacks to our decision to focus on personal essays. Although it was clear even before the pandemic, COVID-19 has highlighted that a path for quick dissemination of original peer-reviewed research is needed. If existing medical journals do not fill that role, websites that publish and disseminate non–peer-reviewed work (aka, “preprints”) will become the preferred method for distribution of high-impact, timely original research.¹¹ The journal’s pivot to reviewing and publishing personal essays may have kept us from improving our approach to rapid peer review and dissemination. In those early days, however, there was no peer-reviewed work to publish, but there was an intense desire (from our members and physicians generally) for information and stories from the front lines. In a way, the essays we published were early “case reports,” that hypothesized about how we might rethink healthcare delivery in pandemic conditions.

Furthermore, our decision to solicit and publish personal essays addressing shortcomings of the federal response and consequences of the pandemic meant that the Journal of Hospital Medicine became part of the pandemic’s political discourse. As editors, we have historically kept the journal away from political arguments or endorsements. In this case, however, we decided that even if some of the opinions were political, they were an appropriate response to the widespread anti-science rhetoric endorsed by the current administration. The resultant erosion of trust in public health has undoubtedly contributed to persistence of the pandemic.¹² A stance against masks, for example, rejects the recommendations of nearly all scientists in favor of (a selfish and problematic idea of) “self-determination.” Those who proclaim that such a mandate infringes on their personal freedom reject evidence-based recommendations of scientists and disregard public health strategies meant to protect everyone.

As we reflect on the past year, our most important lesson may be that our previous emphasis on publishing high-impact original research likely missed important personal and professional insights, insights that could have changed practice, improved patient experience, and reduced physician burnout. Anecdotes are not scientific evidence, but we have discovered their incredible power to help us learn, empathize, commiserate, and survive. Hospitals learned that they must adapt in the moment, a notion that runs counter to the notoriously slow pace of change in paradigms of healthcare. Hospitalists learned to “find their battle buddies” to ward off isolation and to cherish their teams in the face of overwhelming trauma, an approach requiring empathy, humility, and compassion.¹³ We won’t soon forget that, when things were most dire, it was stories—not data—that gave us hope. We look forward to 2021 with great optimism. New vaccines and new federal leaders who value and respect science give us hope that the end of the pandemic is in sight. We are indebted to all frontline workers who have transformed care delivery and remained courageous in the face of great personal risk. As a journal, we will continue, as one scientist noted, to use our “platform for advocacy, unabashedly.”¹⁴

We enter the new year still in the midst of the coronavirus disease 2019 (COVID-19) pandemic and remain humbled by its impact. It is remarkable how much, and how little, has changed. Hospitalists in the early days of the COVID-19 pandemic were struggling. We were caring for patients who were suffering and dying from a new and mysterious disease. There weren’t enough tests (or, if there were tests, there weren’t swabs).¹ We were using protocols for managing respiratory failure that, we would learn later, may not have been the best for improving outcomes. Rumors of unproven therapies came from everywhere: our patients, our colleagues, and even the highest realms of the federal government. We also knew very little about how best to protect ourselves. In many cases, we did not have enough personal protective equipment (PPE). There were no face shields, or “zoom rounds,” or even awareness that we probably shouldn’t sit in the tiny conference room (maskless) discussing patients with the large team of doctors, nurses, respiratory therapists, and social workers.

Perhaps worst of all, we were haunted. We were alarmed by the large numbers of young patients who were ill, and our elderly patients, many of whom we knew and had cared for many times, had suddenly just stopped showing up.² In our free moments, we worried about them; maybe they were afraid to come to the hospital, maybe they were home sick with COVID-19, or maybe they had died alone. And children, initially thought to be spared the most serious consequences of COVID-19, started coming to the hospital with a rare but severe new COVID-19-associated complication, termed multisystem inflammatory syndrome in children (MIS-C). We had to learn to manage yet another manifestation of COVID-19, largely through trial and error.

And, of course, clinical care was only one of our many responsibilities. We were also busy hunting for ventilators, setting up makeshift medical wards and intensive care units, revamping medical education, and scouring the literature for any information to help guide patient care. We worried about getting sick ourselves and bringing the disease home to our families. Our impatience grew as day after day there was no (and still is no) coordinated federal response.

A glimmer of hope slowly emerged. Our colleagues designed and rapidly evaluated respiratory protocols and provided early evidence about the strategies (eg, proning) that were associated with improved outcomes.³ Researchers began to generate knowledge and move us beyond rumors regarding potential therapies. We cheered as our administrators concocted unusual strategies to remedy the PPE and testing shortages.⁴

At the Journal of Hospital Medicine, we were faced with another challenge: How would we describe the chaos and the challenges of being a physician during the COVID-19 era? How would we document the way our colleagues were rising to the challenge and identifying opportunities to rethink hospital care in the United States?

In April, we began to receive a deluge of personal essays from frontline physicians about their experiences with COVID-19. Generally, medical journals publish and disseminate original, high-impact research. Personal essays rarely fit this model. Given the unprecedented circumstances, however, we decided these essays could help chronicle an important moment in medical history. In our May 2020 issue, we published only these essays. We continue to publish them online almost daily.

Some of the essays described how the healthcare system—previously thought to be hyperspecialized, profit-driven, and resistant to change—pivoted within days, as hospitalist physicians trained other physicians to “unspecialize” and pediatricians began to care for adults in an otherwise overwhelmed hospital system.^5,6 Another essay focused on the need to trust that medical students who had graduated early would be able to function as physicians.⁷ And yet another essay expressed concern about the widespread use of unproven therapies in hospitalized patients. “Even in times of global pandemic, we need to consider potential harms and adverse consequences of novel treatments,’’ the physicians wrote. “Sometimes inaction is preferable to action.”⁸

Several essays reflected on the impact of the pandemic on healthcare disparities, suggesting that the pandemic had made (the well-known but often ignored) differences in health outcomes between White patients and racial minorities more obvious. Still another essay reflected on the intersection between structural racism, poor access to care, and interpersonal racism, describing the grief caused by losses of Black lives to both police violence and COVID-19.⁹

There also were personal stories of hardship and survival. One hospitalist physician with asthma described coughing as ``the new leprosy.”¹⁰ She wrote, “This is a particularly unpropitious time in history to be a Chinese-American doctor who can’t stop coughing.”

There were drawbacks to our decision to focus on personal essays. Although it was clear even before the pandemic, COVID-19 has highlighted that a path for quick dissemination of original peer-reviewed research is needed. If existing medical journals do not fill that role, websites that publish and disseminate non–peer-reviewed work (aka, “preprints”) will become the preferred method for distribution of high-impact, timely original research.¹¹ The journal’s pivot to reviewing and publishing personal essays may have kept us from improving our approach to rapid peer review and dissemination. In those early days, however, there was no peer-reviewed work to publish, but there was an intense desire (from our members and physicians generally) for information and stories from the front lines. In a way, the essays we published were early “case reports,” that hypothesized about how we might rethink healthcare delivery in pandemic conditions.

Furthermore, our decision to solicit and publish personal essays addressing shortcomings of the federal response and consequences of the pandemic meant that the Journal of Hospital Medicine became part of the pandemic’s political discourse. As editors, we have historically kept the journal away from political arguments or endorsements. In this case, however, we decided that even if some of the opinions were political, they were an appropriate response to the widespread anti-science rhetoric endorsed by the current administration. The resultant erosion of trust in public health has undoubtedly contributed to persistence of the pandemic.¹² A stance against masks, for example, rejects the recommendations of nearly all scientists in favor of (a selfish and problematic idea of) “self-determination.” Those who proclaim that such a mandate infringes on their personal freedom reject evidence-based recommendations of scientists and disregard public health strategies meant to protect everyone.

As we reflect on the past year, our most important lesson may be that our previous emphasis on publishing high-impact original research likely missed important personal and professional insights, insights that could have changed practice, improved patient experience, and reduced physician burnout. Anecdotes are not scientific evidence, but we have discovered their incredible power to help us learn, empathize, commiserate, and survive. Hospitals learned that they must adapt in the moment, a notion that runs counter to the notoriously slow pace of change in paradigms of healthcare. Hospitalists learned to “find their battle buddies” to ward off isolation and to cherish their teams in the face of overwhelming trauma, an approach requiring empathy, humility, and compassion.¹³ We won’t soon forget that, when things were most dire, it was stories—not data—that gave us hope. We look forward to 2021 with great optimism. New vaccines and new federal leaders who value and respect science give us hope that the end of the pandemic is in sight. We are indebted to all frontline workers who have transformed care delivery and remained courageous in the face of great personal risk. As a journal, we will continue, as one scientist noted, to use our “platform for advocacy, unabashedly.”¹⁴

We enter the new year still in the midst of the coronavirus disease 2019 (COVID-19) pandemic and remain humbled by its impact. It is remarkable how much, and how little, has changed. Hospitalists in the early days of the COVID-19 pandemic were struggling. We were caring for patients who were suffering and dying from a new and mysterious disease. There weren’t enough tests (or, if there were tests, there weren’t swabs).¹ We were using protocols for managing respiratory failure that, we would learn later, may not have been the best for improving outcomes. Rumors of unproven therapies came from everywhere: our patients, our colleagues, and even the highest realms of the federal government. We also knew very little about how best to protect ourselves. In many cases, we did not have enough personal protective equipment (PPE). There were no face shields, or “zoom rounds,” or even awareness that we probably shouldn’t sit in the tiny conference room (maskless) discussing patients with the large team of doctors, nurses, respiratory therapists, and social workers.

Perhaps worst of all, we were haunted. We were alarmed by the large numbers of young patients who were ill, and our elderly patients, many of whom we knew and had cared for many times, had suddenly just stopped showing up.² In our free moments, we worried about them; maybe they were afraid to come to the hospital, maybe they were home sick with COVID-19, or maybe they had died alone. And children, initially thought to be spared the most serious consequences of COVID-19, started coming to the hospital with a rare but severe new COVID-19-associated complication, termed multisystem inflammatory syndrome in children (MIS-C). We had to learn to manage yet another manifestation of COVID-19, largely through trial and error.

And, of course, clinical care was only one of our many responsibilities. We were also busy hunting for ventilators, setting up makeshift medical wards and intensive care units, revamping medical education, and scouring the literature for any information to help guide patient care. We worried about getting sick ourselves and bringing the disease home to our families. Our impatience grew as day after day there was no (and still is no) coordinated federal response.

A glimmer of hope slowly emerged. Our colleagues designed and rapidly evaluated respiratory protocols and provided early evidence about the strategies (eg, proning) that were associated with improved outcomes.³ Researchers began to generate knowledge and move us beyond rumors regarding potential therapies. We cheered as our administrators concocted unusual strategies to remedy the PPE and testing shortages.⁴

At the Journal of Hospital Medicine, we were faced with another challenge: How would we describe the chaos and the challenges of being a physician during the COVID-19 era? How would we document the way our colleagues were rising to the challenge and identifying opportunities to rethink hospital care in the United States?

In April, we began to receive a deluge of personal essays from frontline physicians about their experiences with COVID-19. Generally, medical journals publish and disseminate original, high-impact research. Personal essays rarely fit this model. Given the unprecedented circumstances, however, we decided these essays could help chronicle an important moment in medical history. In our May 2020 issue, we published only these essays. We continue to publish them online almost daily.

Some of the essays described how the healthcare system—previously thought to be hyperspecialized, profit-driven, and resistant to change—pivoted within days, as hospitalist physicians trained other physicians to “unspecialize” and pediatricians began to care for adults in an otherwise overwhelmed hospital system.^5,6 Another essay focused on the need to trust that medical students who had graduated early would be able to function as physicians.⁷ And yet another essay expressed concern about the widespread use of unproven therapies in hospitalized patients. “Even in times of global pandemic, we need to consider potential harms and adverse consequences of novel treatments,’’ the physicians wrote. “Sometimes inaction is preferable to action.”⁸

Several essays reflected on the impact of the pandemic on healthcare disparities, suggesting that the pandemic had made (the well-known but often ignored) differences in health outcomes between White patients and racial minorities more obvious. Still another essay reflected on the intersection between structural racism, poor access to care, and interpersonal racism, describing the grief caused by losses of Black lives to both police violence and COVID-19.⁹

There also were personal stories of hardship and survival. One hospitalist physician with asthma described coughing as ``the new leprosy.”¹⁰ She wrote, “This is a particularly unpropitious time in history to be a Chinese-American doctor who can’t stop coughing.”

There were drawbacks to our decision to focus on personal essays. Although it was clear even before the pandemic, COVID-19 has highlighted that a path for quick dissemination of original peer-reviewed research is needed. If existing medical journals do not fill that role, websites that publish and disseminate non–peer-reviewed work (aka, “preprints”) will become the preferred method for distribution of high-impact, timely original research.¹¹ The journal’s pivot to reviewing and publishing personal essays may have kept us from improving our approach to rapid peer review and dissemination. In those early days, however, there was no peer-reviewed work to publish, but there was an intense desire (from our members and physicians generally) for information and stories from the front lines. In a way, the essays we published were early “case reports,” that hypothesized about how we might rethink healthcare delivery in pandemic conditions.

Furthermore, our decision to solicit and publish personal essays addressing shortcomings of the federal response and consequences of the pandemic meant that the Journal of Hospital Medicine became part of the pandemic’s political discourse. As editors, we have historically kept the journal away from political arguments or endorsements. In this case, however, we decided that even if some of the opinions were political, they were an appropriate response to the widespread anti-science rhetoric endorsed by the current administration. The resultant erosion of trust in public health has undoubtedly contributed to persistence of the pandemic.¹² A stance against masks, for example, rejects the recommendations of nearly all scientists in favor of (a selfish and problematic idea of) “self-determination.” Those who proclaim that such a mandate infringes on their personal freedom reject evidence-based recommendations of scientists and disregard public health strategies meant to protect everyone.

As we reflect on the past year, our most important lesson may be that our previous emphasis on publishing high-impact original research likely missed important personal and professional insights, insights that could have changed practice, improved patient experience, and reduced physician burnout. Anecdotes are not scientific evidence, but we have discovered their incredible power to help us learn, empathize, commiserate, and survive. Hospitals learned that they must adapt in the moment, a notion that runs counter to the notoriously slow pace of change in paradigms of healthcare. Hospitalists learned to “find their battle buddies” to ward off isolation and to cherish their teams in the face of overwhelming trauma, an approach requiring empathy, humility, and compassion.¹³ We won’t soon forget that, when things were most dire, it was stories—not data—that gave us hope. We look forward to 2021 with great optimism. New vaccines and new federal leaders who value and respect science give us hope that the end of the pandemic is in sight. We are indebted to all frontline workers who have transformed care delivery and remained courageous in the face of great personal risk. As a journal, we will continue, as one scientist noted, to use our “platform for advocacy, unabashedly.”¹⁴

Poor sleep health and attention regulation problems are common in young children with atopic dermatitis (AD), and the burden intensifies with worse severity, results from a national survey demonstrated.

“We think it’s important for dermatologists and pediatricians to be monitoring children with AD for sleep and attention dysregulation,” Nina Y. Zhou said during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium. “It’s also important to highlight sleep hygiene habits to improve sleep health overall.”

In an effort to determine the impact of AD severity on these symptoms in young children with AD and characterize sleep health and attention regulation behaviors, Ms. Zhou, a medical student at Northwestern University, Chicago, and colleagues drew from a national survey distributed via panel company OP4G and the National Eczema Association that was conducted with parents of 60 children with AD aged 1-5 years. Questionnaires included the Patient Reported Outcomes Measurement Information System (PROMIS) Early Childhood Sleep Health Measures to assess sleep health, the Peak Pruritus NRS to measure itch severity, and the Multidimensional Assessment Profile of Attention Regulation (MAPS-AR) to measure attention dysregulation related to inattention and hyperactivity. The researchers performed linear regression to determine the predictors of sleep health and attention dysregulation.

The mean age of 60 children was 3 years, 55% were male, 32% were black, 42% had severe disease, 42% had moderate disease, and 16% had mild disease. Children with more extensive AD were significantly more likely to report worse sleep disturbance. The proportion of children who reported sleep disturbance on at least 5 nights per week was 67% among those with severe AD, 24% among those with moderate AD, and 0% among those with mild AD.

In addition, 72% of parents of children with severe AD reported trouble paying attention at least 3 times per week “no matter what was going on,” compared with 24% of those with moderate AD and none of those with mild AD.

Parents of children with more severe AD reported more itch-related burden and significantly decreased quality of life for their children. For example, 76% of parents with children who had severe AD reported “because of itch, their child was frustrated,” compared to 44% of those with moderate AD and 10% with mild AD.

In fully adjusted linear regression analysis, the strongest predictors of sleep disturbance were AD severity (unstandardized beta value = 0.79, P less than .01) and being Black (unstandardized beta value = 3.89, P = .03). AD severity (unstandardized beta value = 1.22, P less than .01) and being Black (unstandardized beta value = 7.79, P less than .01) also predicted more attention dysregulation.

Household income appeared to differ significantly based on AD severity groups. “If you have mild AD, you are more likely to come from a higher income household,” Ms. Zhou said.

She concluded her presentation by calling for future studies with larger samples sizes to establish causality and directional effects between AD severity, itch, sleep, race, and attention.

The study was funded by the Agency for Healthcare Research and Quality. Ms. Zhou reported having no financial disclosures.

[email protected]

Poor sleep health and attention regulation problems are common in young children with atopic dermatitis (AD), and the burden intensifies with worse severity, results from a national survey demonstrated.

“We think it’s important for dermatologists and pediatricians to be monitoring children with AD for sleep and attention dysregulation,” Nina Y. Zhou said during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium. “It’s also important to highlight sleep hygiene habits to improve sleep health overall.”

In an effort to determine the impact of AD severity on these symptoms in young children with AD and characterize sleep health and attention regulation behaviors, Ms. Zhou, a medical student at Northwestern University, Chicago, and colleagues drew from a national survey distributed via panel company OP4G and the National Eczema Association that was conducted with parents of 60 children with AD aged 1-5 years. Questionnaires included the Patient Reported Outcomes Measurement Information System (PROMIS) Early Childhood Sleep Health Measures to assess sleep health, the Peak Pruritus NRS to measure itch severity, and the Multidimensional Assessment Profile of Attention Regulation (MAPS-AR) to measure attention dysregulation related to inattention and hyperactivity. The researchers performed linear regression to determine the predictors of sleep health and attention dysregulation.

The mean age of 60 children was 3 years, 55% were male, 32% were black, 42% had severe disease, 42% had moderate disease, and 16% had mild disease. Children with more extensive AD were significantly more likely to report worse sleep disturbance. The proportion of children who reported sleep disturbance on at least 5 nights per week was 67% among those with severe AD, 24% among those with moderate AD, and 0% among those with mild AD.

In addition, 72% of parents of children with severe AD reported trouble paying attention at least 3 times per week “no matter what was going on,” compared with 24% of those with moderate AD and none of those with mild AD.

Parents of children with more severe AD reported more itch-related burden and significantly decreased quality of life for their children. For example, 76% of parents with children who had severe AD reported “because of itch, their child was frustrated,” compared to 44% of those with moderate AD and 10% with mild AD.

In fully adjusted linear regression analysis, the strongest predictors of sleep disturbance were AD severity (unstandardized beta value = 0.79, P less than .01) and being Black (unstandardized beta value = 3.89, P = .03). AD severity (unstandardized beta value = 1.22, P less than .01) and being Black (unstandardized beta value = 7.79, P less than .01) also predicted more attention dysregulation.

Household income appeared to differ significantly based on AD severity groups. “If you have mild AD, you are more likely to come from a higher income household,” Ms. Zhou said.

She concluded her presentation by calling for future studies with larger samples sizes to establish causality and directional effects between AD severity, itch, sleep, race, and attention.

The study was funded by the Agency for Healthcare Research and Quality. Ms. Zhou reported having no financial disclosures.

[email protected]

Poor sleep health and attention regulation problems are common in young children with atopic dermatitis (AD), and the burden intensifies with worse severity, results from a national survey demonstrated.

“We think it’s important for dermatologists and pediatricians to be monitoring children with AD for sleep and attention dysregulation,” Nina Y. Zhou said during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium. “It’s also important to highlight sleep hygiene habits to improve sleep health overall.”

In an effort to determine the impact of AD severity on these symptoms in young children with AD and characterize sleep health and attention regulation behaviors, Ms. Zhou, a medical student at Northwestern University, Chicago, and colleagues drew from a national survey distributed via panel company OP4G and the National Eczema Association that was conducted with parents of 60 children with AD aged 1-5 years. Questionnaires included the Patient Reported Outcomes Measurement Information System (PROMIS) Early Childhood Sleep Health Measures to assess sleep health, the Peak Pruritus NRS to measure itch severity, and the Multidimensional Assessment Profile of Attention Regulation (MAPS-AR) to measure attention dysregulation related to inattention and hyperactivity. The researchers performed linear regression to determine the predictors of sleep health and attention dysregulation.

The mean age of 60 children was 3 years, 55% were male, 32% were black, 42% had severe disease, 42% had moderate disease, and 16% had mild disease. Children with more extensive AD were significantly more likely to report worse sleep disturbance. The proportion of children who reported sleep disturbance on at least 5 nights per week was 67% among those with severe AD, 24% among those with moderate AD, and 0% among those with mild AD.

In addition, 72% of parents of children with severe AD reported trouble paying attention at least 3 times per week “no matter what was going on,” compared with 24% of those with moderate AD and none of those with mild AD.

Parents of children with more severe AD reported more itch-related burden and significantly decreased quality of life for their children. For example, 76% of parents with children who had severe AD reported “because of itch, their child was frustrated,” compared to 44% of those with moderate AD and 10% with mild AD.

In fully adjusted linear regression analysis, the strongest predictors of sleep disturbance were AD severity (unstandardized beta value = 0.79, P less than .01) and being Black (unstandardized beta value = 3.89, P = .03). AD severity (unstandardized beta value = 1.22, P less than .01) and being Black (unstandardized beta value = 7.79, P less than .01) also predicted more attention dysregulation.

Household income appeared to differ significantly based on AD severity groups. “If you have mild AD, you are more likely to come from a higher income household,” Ms. Zhou said.

She concluded her presentation by calling for future studies with larger samples sizes to establish causality and directional effects between AD severity, itch, sleep, race, and attention.

The study was funded by the Agency for Healthcare Research and Quality. Ms. Zhou reported having no financial disclosures.

[email protected]

Mortality rates for inpatients with COVID-19 dropped significantly during the first 6 months of the pandemic, but outcomes depend on the hospital where patients receive care, new data show.

“[T]he characteristic that is most associated with poor or worsening hospital outcomes is high or increasing community case rates,” write David A. Asch, MD, MBA, executive director of the Center for Health Care Innovation at the University of Pennsylvania in Philadelphia, and colleagues.

The relationship between COVID-19 mortality rates and local disease prevalence suggests that “hospitals do worse when they are burdened with cases and is consistent with imperatives to flatten the curve,” the authors continue. “As case rates of COVID-19 increase across the nation, hospital mortality outcomes may worsen.”

The researchers published their study online December 22 in JAMA Internal Medicine.

The quick and substantial improvement in survival “is a tribute in part to new science — for example, the science that revealed the benefits of dexamethasone,” Asch told Medscape Medical News. “But it’s also a tribute to the doctors and nurses in the hospitals who developed experience. It’s a cliché to refer to them as heroes, but that is what they are. The science and the heroic experience continues on, and so I’m optimistic that we’ll see even more improvement over time.”

However, the data also indicate that “with lots of disease in the community, hospitals may have a harder time keeping patients alive,” Asch said.  “And of course the reason this is bad news is that community level case rates are rising all over, and in some cases at rapid rates. With that rise, we might be giving back some of our past gains in survival — just as the vaccine is beginning to be distributed.”
 

Examining mortality trends

The researchers analyzed administrative claims data from a large national health insurer. They included data from 38,517 adults who were admitted with COVID-19 to 955 US hospitals between January 1 and June 30 of this year. The investigators estimated hospitals’ risk-standardized rate of 30-day in-hospital mortality or referral to hospice, adjusted for patient-level characteristics.

Overall, 3179 patients (8.25%) died, and 1433 patients (3.7%) were referred to hospice. Risk-standardized mortality or hospice referral rates for individual hospitals ranged from 5.7% to 24.7%. The average rate was 9.1% in the best-performing quintile, compared with 15.7% in the worst-performing quintile.

In a subset of 398 hospitals that had at least 10 patients admitted for COVID-19 during early (January 1 through April 30) and later periods (between May 1 and June 30), rates in all but one hospital improved, and 94% improved by at least 25%. The average risk-standardized event rate declined from 16.6% to 9.3%.

“That rate of relative improvement is striking and encouraging, but perhaps not surprising,” Asch and coauthors write. “Early efforts at treating patients with COVID-19 were based on experience with previously known causes of severe respiratory illness. Later efforts could draw on experiences specific to SARS-CoV-2 infection.”

For instance, doctors tried different inpatient management approaches, such as early vs late assisted ventilation, differences in oxygen flow, prone or supine positioning, and anticoagulation. “Those efforts varied in how systematically they were evaluated, but our results suggest that valuable experience was gained,” the authors note.

In addition, variation between hospitals could reflect differences in quality or different admission thresholds, they continue.

The study provides “a reason for optimism that our healthcare system has improved in our ability to care for persons with COVID-19,” write Leon Boudourakis, MD, MHS, and Amit Uppal, MD, in a related commentary. Boudourakis and Uppal are both affiliated with NYC Health + Hospitals in New York City and with SUNY Downstate and New York University School of Medicine, respectively.

Similar improvements in mortality rates have been reported in the United Kingdom and in a New York City hospital system, the editorialists note. The lower mortality rates may represent clinical, healthcare system, and epidemiologic trends.

“Since the first wave of serious COVID-19 cases, physicians have learned a great deal about the best ways to treat this serious infection,” they say. “Steroids may decrease mortality in patients with respiratory failure. Remdesivir may shorten hospitalizations of patients with serious illness. Anticoagulation and prone positioning may help certain patients. Using noninvasive ventilation and high-flow oxygen therapy may spare subsets of patients from the harms of intubation, such as ventilator-induced lung injury.»
 

Overwhelmed hospitals

“Hospitals do not perform as well when they are overwhelmed,” which may be a reason for the correlation between community prevalence and mortality rates, Boudourakis and Uppal suggested. “In particular, patients with a precarious respiratory status require expert, meticulous therapy to avoid intubation; those who undergo intubation or have kidney failure require nuanced and timely expert care with ventilatory adjustments and kidney replacement therapy, which are difficult to perform optimally when hospital capacity is strained.”

Although the death rate has fallen to about 9% for hospitalized patients, “9% is still high,” Asch said.

“Our results show that hospitals can’t do it on their own,” Asch said. “They need all of us to keep the community spread of the disease down. The right answer now is the right answer since the beginning of the pandemic: Keep your distance, wash your hands, and wear a mask.”

Asch, Boudourakis, and Uppal have disclosed no relevant financial relationships. A study coauthor reported personal fees and grants from pharmaceutical companies outside the submitted work.

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

Mortality rates for inpatients with COVID-19 dropped significantly during the first 6 months of the pandemic, but outcomes depend on the hospital where patients receive care, new data show.

“[T]he characteristic that is most associated with poor or worsening hospital outcomes is high or increasing community case rates,” write David A. Asch, MD, MBA, executive director of the Center for Health Care Innovation at the University of Pennsylvania in Philadelphia, and colleagues.

The relationship between COVID-19 mortality rates and local disease prevalence suggests that “hospitals do worse when they are burdened with cases and is consistent with imperatives to flatten the curve,” the authors continue. “As case rates of COVID-19 increase across the nation, hospital mortality outcomes may worsen.”

The researchers published their study online December 22 in JAMA Internal Medicine.

The quick and substantial improvement in survival “is a tribute in part to new science — for example, the science that revealed the benefits of dexamethasone,” Asch told Medscape Medical News. “But it’s also a tribute to the doctors and nurses in the hospitals who developed experience. It’s a cliché to refer to them as heroes, but that is what they are. The science and the heroic experience continues on, and so I’m optimistic that we’ll see even more improvement over time.”

However, the data also indicate that “with lots of disease in the community, hospitals may have a harder time keeping patients alive,” Asch said.  “And of course the reason this is bad news is that community level case rates are rising all over, and in some cases at rapid rates. With that rise, we might be giving back some of our past gains in survival — just as the vaccine is beginning to be distributed.”
 

Examining mortality trends

The researchers analyzed administrative claims data from a large national health insurer. They included data from 38,517 adults who were admitted with COVID-19 to 955 US hospitals between January 1 and June 30 of this year. The investigators estimated hospitals’ risk-standardized rate of 30-day in-hospital mortality or referral to hospice, adjusted for patient-level characteristics.

Overall, 3179 patients (8.25%) died, and 1433 patients (3.7%) were referred to hospice. Risk-standardized mortality or hospice referral rates for individual hospitals ranged from 5.7% to 24.7%. The average rate was 9.1% in the best-performing quintile, compared with 15.7% in the worst-performing quintile.

In a subset of 398 hospitals that had at least 10 patients admitted for COVID-19 during early (January 1 through April 30) and later periods (between May 1 and June 30), rates in all but one hospital improved, and 94% improved by at least 25%. The average risk-standardized event rate declined from 16.6% to 9.3%.

“That rate of relative improvement is striking and encouraging, but perhaps not surprising,” Asch and coauthors write. “Early efforts at treating patients with COVID-19 were based on experience with previously known causes of severe respiratory illness. Later efforts could draw on experiences specific to SARS-CoV-2 infection.”

For instance, doctors tried different inpatient management approaches, such as early vs late assisted ventilation, differences in oxygen flow, prone or supine positioning, and anticoagulation. “Those efforts varied in how systematically they were evaluated, but our results suggest that valuable experience was gained,” the authors note.

In addition, variation between hospitals could reflect differences in quality or different admission thresholds, they continue.

The study provides “a reason for optimism that our healthcare system has improved in our ability to care for persons with COVID-19,” write Leon Boudourakis, MD, MHS, and Amit Uppal, MD, in a related commentary. Boudourakis and Uppal are both affiliated with NYC Health + Hospitals in New York City and with SUNY Downstate and New York University School of Medicine, respectively.

Similar improvements in mortality rates have been reported in the United Kingdom and in a New York City hospital system, the editorialists note. The lower mortality rates may represent clinical, healthcare system, and epidemiologic trends.

“Since the first wave of serious COVID-19 cases, physicians have learned a great deal about the best ways to treat this serious infection,” they say. “Steroids may decrease mortality in patients with respiratory failure. Remdesivir may shorten hospitalizations of patients with serious illness. Anticoagulation and prone positioning may help certain patients. Using noninvasive ventilation and high-flow oxygen therapy may spare subsets of patients from the harms of intubation, such as ventilator-induced lung injury.»
 

Overwhelmed hospitals

“Hospitals do not perform as well when they are overwhelmed,” which may be a reason for the correlation between community prevalence and mortality rates, Boudourakis and Uppal suggested. “In particular, patients with a precarious respiratory status require expert, meticulous therapy to avoid intubation; those who undergo intubation or have kidney failure require nuanced and timely expert care with ventilatory adjustments and kidney replacement therapy, which are difficult to perform optimally when hospital capacity is strained.”

Although the death rate has fallen to about 9% for hospitalized patients, “9% is still high,” Asch said.

“Our results show that hospitals can’t do it on their own,” Asch said. “They need all of us to keep the community spread of the disease down. The right answer now is the right answer since the beginning of the pandemic: Keep your distance, wash your hands, and wear a mask.”

Asch, Boudourakis, and Uppal have disclosed no relevant financial relationships. A study coauthor reported personal fees and grants from pharmaceutical companies outside the submitted work.

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

Mortality rates for inpatients with COVID-19 dropped significantly during the first 6 months of the pandemic, but outcomes depend on the hospital where patients receive care, new data show.

“[T]he characteristic that is most associated with poor or worsening hospital outcomes is high or increasing community case rates,” write David A. Asch, MD, MBA, executive director of the Center for Health Care Innovation at the University of Pennsylvania in Philadelphia, and colleagues.

The relationship between COVID-19 mortality rates and local disease prevalence suggests that “hospitals do worse when they are burdened with cases and is consistent with imperatives to flatten the curve,” the authors continue. “As case rates of COVID-19 increase across the nation, hospital mortality outcomes may worsen.”

The researchers published their study online December 22 in JAMA Internal Medicine.

The quick and substantial improvement in survival “is a tribute in part to new science — for example, the science that revealed the benefits of dexamethasone,” Asch told Medscape Medical News. “But it’s also a tribute to the doctors and nurses in the hospitals who developed experience. It’s a cliché to refer to them as heroes, but that is what they are. The science and the heroic experience continues on, and so I’m optimistic that we’ll see even more improvement over time.”

However, the data also indicate that “with lots of disease in the community, hospitals may have a harder time keeping patients alive,” Asch said.  “And of course the reason this is bad news is that community level case rates are rising all over, and in some cases at rapid rates. With that rise, we might be giving back some of our past gains in survival — just as the vaccine is beginning to be distributed.”
 

Examining mortality trends

The researchers analyzed administrative claims data from a large national health insurer. They included data from 38,517 adults who were admitted with COVID-19 to 955 US hospitals between January 1 and June 30 of this year. The investigators estimated hospitals’ risk-standardized rate of 30-day in-hospital mortality or referral to hospice, adjusted for patient-level characteristics.

Overall, 3179 patients (8.25%) died, and 1433 patients (3.7%) were referred to hospice. Risk-standardized mortality or hospice referral rates for individual hospitals ranged from 5.7% to 24.7%. The average rate was 9.1% in the best-performing quintile, compared with 15.7% in the worst-performing quintile.

In a subset of 398 hospitals that had at least 10 patients admitted for COVID-19 during early (January 1 through April 30) and later periods (between May 1 and June 30), rates in all but one hospital improved, and 94% improved by at least 25%. The average risk-standardized event rate declined from 16.6% to 9.3%.

“That rate of relative improvement is striking and encouraging, but perhaps not surprising,” Asch and coauthors write. “Early efforts at treating patients with COVID-19 were based on experience with previously known causes of severe respiratory illness. Later efforts could draw on experiences specific to SARS-CoV-2 infection.”

For instance, doctors tried different inpatient management approaches, such as early vs late assisted ventilation, differences in oxygen flow, prone or supine positioning, and anticoagulation. “Those efforts varied in how systematically they were evaluated, but our results suggest that valuable experience was gained,” the authors note.

In addition, variation between hospitals could reflect differences in quality or different admission thresholds, they continue.

The study provides “a reason for optimism that our healthcare system has improved in our ability to care for persons with COVID-19,” write Leon Boudourakis, MD, MHS, and Amit Uppal, MD, in a related commentary. Boudourakis and Uppal are both affiliated with NYC Health + Hospitals in New York City and with SUNY Downstate and New York University School of Medicine, respectively.

Similar improvements in mortality rates have been reported in the United Kingdom and in a New York City hospital system, the editorialists note. The lower mortality rates may represent clinical, healthcare system, and epidemiologic trends.

“Since the first wave of serious COVID-19 cases, physicians have learned a great deal about the best ways to treat this serious infection,” they say. “Steroids may decrease mortality in patients with respiratory failure. Remdesivir may shorten hospitalizations of patients with serious illness. Anticoagulation and prone positioning may help certain patients. Using noninvasive ventilation and high-flow oxygen therapy may spare subsets of patients from the harms of intubation, such as ventilator-induced lung injury.»
 

Overwhelmed hospitals

“Hospitals do not perform as well when they are overwhelmed,” which may be a reason for the correlation between community prevalence and mortality rates, Boudourakis and Uppal suggested. “In particular, patients with a precarious respiratory status require expert, meticulous therapy to avoid intubation; those who undergo intubation or have kidney failure require nuanced and timely expert care with ventilatory adjustments and kidney replacement therapy, which are difficult to perform optimally when hospital capacity is strained.”

Although the death rate has fallen to about 9% for hospitalized patients, “9% is still high,” Asch said.

“Our results show that hospitals can’t do it on their own,” Asch said. “They need all of us to keep the community spread of the disease down. The right answer now is the right answer since the beginning of the pandemic: Keep your distance, wash your hands, and wear a mask.”

Asch, Boudourakis, and Uppal have disclosed no relevant financial relationships. A study coauthor reported personal fees and grants from pharmaceutical companies outside the submitted work.

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

Breast cancer recurrence rates are similar with anastrozole and tamoxifen in postmenopausal women with hormone receptor–positive ductal carcinoma in situ (HR-positive DCIS), according to long-term results of the IBIS-II DCIS trial.

“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.

Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.

“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.

She presented these results at the 2020 San Antonio Breast Cancer Symposium.
 

Comparing IBIS-II DCIS with prior results

“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.

However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.

Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”

In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.

The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.

“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
 

IBIS-II DCIS details and results

Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.

The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.

“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”

Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).

Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).

Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.

Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
 

Adverse events could be the deciding factor

“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.

During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.

“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.

She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.

Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.

“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”

The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.

SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.

Breast cancer recurrence rates are similar with anastrozole and tamoxifen in postmenopausal women with hormone receptor–positive ductal carcinoma in situ (HR-positive DCIS), according to long-term results of the IBIS-II DCIS trial.

“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.

Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.

“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.

She presented these results at the 2020 San Antonio Breast Cancer Symposium.
 

Comparing IBIS-II DCIS with prior results

“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.

However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.

Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”

In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.

The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.

“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
 

IBIS-II DCIS details and results

Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.

The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.

“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”

Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).

Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).

Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.

Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
 

Adverse events could be the deciding factor

“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.

During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.

“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.

She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.

Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.

“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”

The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.

SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.

Breast cancer recurrence rates are similar with anastrozole and tamoxifen in postmenopausal women with hormone receptor–positive ductal carcinoma in situ (HR-positive DCIS), according to long-term results of the IBIS-II DCIS trial.

“Our analysis shows that there was really no significant difference in recurrences,” said investigator Ivana Sestak, PhD, of Queen Mary University of London.

Similarly, there were no significant differences in overall deaths or breast cancer deaths. On the other hand, there were “clear differences” in adverse events with the two treatments, Dr. Sestak said.

“[W]e observed an excess of endometrial cancer and ovarian cancers in women who were randomized to tamoxifen and an excess of fractures, strokes, and transient ischemic attacks for women who were randomized to anastrozole,” Dr. Sestak said.

She presented these results at the 2020 San Antonio Breast Cancer Symposium.
 

Comparing IBIS-II DCIS with prior results

“The long-term results of the IBIS-II [DCIS] trial are consistent with previous results,” said Halle Moore, MD, of the Cleveland Clinic, who was not involved in this study.

However, the results do contrast with the findings of the NSABP-B35 study, “which demonstrated a very modest advantage to anastrozole that was mostly limited to younger postmenopausal women,” she said.

Indeed, a significant 27% reduction in recurrence was seen with anastrozole, compared with tamoxifen at a median of 9 years of follow-up in the NSABP-B35 study. But, as Dr. Sestak pointed out, that reduction “was mainly observed during the posttreatment follow-up period and not during the active treatment period.”

In the IBIS-II DCIS study, there was a nonsignificant 11% reduction in breast cancer recurrence with anastrozole.

The investigators did examine the potential effect of age on the rate of breast cancer recurrence, but no significant differences were found. They also looked at the active and post–endocrine therapy treatment periods, all showing no benefit of one drug over the other.

“So we clearly cannot replicate the findings of the NSABP-B35 study,” Dr. Sestak acknowledged.
 

IBIS-II DCIS details and results

Aromatase inhibitors such as anastrozole have been shown to be more effective than tamoxifen for preventing recurrence in postmenopausal HR+ women with invasive breast cancer, but it wasn’t previously known if this included women with HR-positive DCIS.

The IBIS-II DCIS study was therefore designed to determine if there was any advantage of anastrazole over tamoxifen. The phase 3 trial enrolled 2,980 postmenopausal women with HR-positive DCIS. They were randomized to 5 years of anastrozole or 5 years of tamoxifen.

“Women were followed up during this active period of treatment by clinic visits,” explained Dr. Sestak. “Thereafter, we collected data via questionnaire, registry data sets, and clinic visits.”

Baseline characteristics were similar between the treatment arms. The median age was about 60 years in both arms. Similar proportions of patients had received hormone replacement therapy (44.2% in the tamoxifen arm and 46.8% in the anastrozole arm) or undergone radiotherapy (71.5% and 70.9%, respectively).

Results showed little difference in breast cancer recurrence rates. At a median follow-up of 11.6 years, the rate of recurrence was 9.7% with tamoxifen and 8.5% with anastrozole (hazard ratio, 0.89; P = .401).

Trends were seen favoring anastrozole in estrogen receptor–positive and HER2-negative women, but this was only while women were being actively treated.

Death rates were similar – 4.2% with anastrozole and 4.5% with tamoxifen (odds ratio, 0.93). There were three breast cancer deaths in each treatment arm.
 

Adverse events could be the deciding factor

“The main take-away from this presentation is that choice of adjuvant endocrine therapy for DCIS should be individualized based primarily on the different side effect profiles of the two medications,” Dr. Moore said.

During the trial, “a significant 34% increase in fractures was observed in women who received anastrozole, compared to tamoxifen [HR, 1.34; P = .013],” Dr. Sestak said.

“We also observed a threefold increase in strokes and transient ischemic attacks with anastrozole, compared to tamoxifen [HR, 3.10; P = .021 for both strokes and transient ischemic attacks],” Dr. Sestak added.

She acknowledged that this finding is inconsistent with what is known about aromatase inhibitors in general. It could be that, rather than anastrozole raising the risk of strokes and transient ischemic attacks, tamoxifen was having a beneficial effect. This could be a result of tamoxifen improving endothelial function by increasing vasodilation, “but it is really not clear what the mechanism is,” Dr. Sestak said.

Also contrary to what is known about tamoxifen was an excess of deaths because of endometrial cancer or ovarian cancers. Wherever possible, the pathology reports had been requested to confirm the cause of death, “so we are pretty sure that they are true ovarian cancers and not some other abdominal tumors,” Dr. Sestak said.

“We did observe very clear differences in terms of adverse events,” she said, adding that “improved understanding of adverse event profiles will help patients with HR-positive DCIS to make an informed decision regarding their treatment.”

The IBIS-II DCIS trial was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, AstraZeneca, and Sanofi Aventis. Two investigators disclosed relationships with AstraZeneca, and one disclosed a relationship with Cancer Research UK. Dr. Sestak and Dr. Moore had no relevant disclosures.

SOURCE: Sestak I et al. SABCS 2020, Abstract GS2-02.

Shared medical appointments (SMAs) are an acceptable way to receive treatment for opioid use disorder (OUD), new research suggests.

In a survey study, participants attending an urban outpatient buprenorphine clinic reported a high degree of satisfaction with SMAs. However, the majority also reported they preferred individual appointments.

Still, SMAs may serve a role in providing comprehensive care for certain subpopulations with OUD who are prone to isolation and may also increase capacity to treat more patients with a substance use disorder (SUD), said coinvestigator Serra Akyar, MD, Northwell Health Staten Island University Hospital, New York.

“By providing education and a forum for sharing, SMAs can lead to changes in behavior and enhance and reinforce coping and problem-solving skills,” Dr. Akyar said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

SMA vs. group therapy

SMA is not a form of group therapy, Dr. Akyar noted. Group therapy has a psychotherapy component and is led by a therapist. SMAs do not have a psychotherapeutic or a behavioral therapy component but provide education and an opportunity for sharing personal experiences of recovery.

“For example, the doctor participating in the group describes what happens in the brain to drive addiction and fellow participants share their personal anecdotes of recovery, including their struggles and successes,” Dr. Akyar said.

“While SMAs and group therapy seem similar, using the terms interchangeably would be incorrect given the differences in the type of care each group provides,” she added.

Recent research on SMAs for OUD is limited. Although previous studies have shown that the practice is highly acceptable and has comparable or better retention in care rates with buprenorphine versus individual appointments, these studies have been conducted in predominantly White populations and in suburban settings.

For the new study, the investigators wanted to examine how acceptable SMAs for OUD would be in an urban setting involving predominantly racial and ethnic minorities.

They administered a 15-minute survey to patients with OUD who were attending the Comprehensive Addiction Resources and Education Center, an outpatient psychiatry clinic located at New Jersey Medical School, from December 2019 to February 2020.

Of the 42 participants who initially consented, 39 completed the survey. The majority of the responders were Black (64.1%), had an annual income that was less than $20,000 (61.5%), and/or were unemployed or disabled (69.3%).

Most of the participants agreed or strongly agreed with the following statements:

• Scheduling appointments for SMAs is easy.
• I gain valuable information from the responses to other patients’ questions in SMAs.
• There is enough time for questions during SMAs.
• I gain valuable information from the doctor and social worker in SMAs.
• My medical needs are met during SMAs.
• I would recommend an SMA to other patients.
• Since starting SMAs, I find it easier to stick to my treatment plan.
• I have a lot of support outside of SMAs.
• People in SMAs give me the support I need to stick to my treatment plan.

Interestingly, despite the overall high satisfaction with SMAs, just 33% of participants said they preferred them to one-on-one visits, Dr. Akyar noted.

Further analyses showed that total satisfaction scores were positively associated with older age, being on disability, or being in retirement.
 

Bridging the gap

In a comment, Philip Wong, MD, New Jersey Medical School, Newark, noted that a more widespread use of SMAs could potentially bridge the treatment gap that currently exists in the United States.

“For providers, SMAs help reduce costs, improve productivity, prevent repeating of common advice, and increase outreach. These are all important at a time when the need for OUD treatment is increasing. This is especially true for places like Newark, which is one of the prime epicenters of the opioid epidemic,” said Dr. Wong.

Although he was not involved with this research, he and his colleagues recently conducted a literature review of publications relating to SMAs and found seven peer-reviewed articles. However, none was appropriately designed to compare SMAs with traditional one-on-one recovery treatment.

“We definitely need more clinical studies to further our understanding of SMAs as a tool for the medication-assisted treatment of opioid use disorder,” Dr. Wong said.

“There are currently a very limited number of physicians who can prescribe medication-assisted treatment in the first place. So, if that one provider can reach a larger community by doing these SMAs, then the potential is very great in terms of addressing the opioid epidemic,” he said.

David Kan, MD, chief medical officer of Bright Heart Health, San Ramon, Calif., agreed.

“SMAs are promising because they are efficient and allow more people to access treatment,” Dr. Kan said in an interview.

“Although the mechanism of SMA satisfaction is unclear, other research shows peer support and groups helpful for SUD treatment as a whole. SMA takes the best of many worlds and increases the potential number of patients treated for SUD,” he said.

Also asked to comment, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, said SMAs “are one of a number of important interventions that should be considered” in order to increase availability and access to medication providers for OUD.

However, more research is needed “to examine the impact on treatment uptake and patient and provider experiences,” said Dr. Lin.

Dr. Akyar, Dr. Wong, Dr. Kan, and Dr. Lin disclosed no relevant financial relationships.

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

Shared medical appointments (SMAs) are an acceptable way to receive treatment for opioid use disorder (OUD), new research suggests.

In a survey study, participants attending an urban outpatient buprenorphine clinic reported a high degree of satisfaction with SMAs. However, the majority also reported they preferred individual appointments.

Still, SMAs may serve a role in providing comprehensive care for certain subpopulations with OUD who are prone to isolation and may also increase capacity to treat more patients with a substance use disorder (SUD), said coinvestigator Serra Akyar, MD, Northwell Health Staten Island University Hospital, New York.

“By providing education and a forum for sharing, SMAs can lead to changes in behavior and enhance and reinforce coping and problem-solving skills,” Dr. Akyar said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

SMA vs. group therapy

SMA is not a form of group therapy, Dr. Akyar noted. Group therapy has a psychotherapy component and is led by a therapist. SMAs do not have a psychotherapeutic or a behavioral therapy component but provide education and an opportunity for sharing personal experiences of recovery.

“For example, the doctor participating in the group describes what happens in the brain to drive addiction and fellow participants share their personal anecdotes of recovery, including their struggles and successes,” Dr. Akyar said.

“While SMAs and group therapy seem similar, using the terms interchangeably would be incorrect given the differences in the type of care each group provides,” she added.

Recent research on SMAs for OUD is limited. Although previous studies have shown that the practice is highly acceptable and has comparable or better retention in care rates with buprenorphine versus individual appointments, these studies have been conducted in predominantly White populations and in suburban settings.

For the new study, the investigators wanted to examine how acceptable SMAs for OUD would be in an urban setting involving predominantly racial and ethnic minorities.

They administered a 15-minute survey to patients with OUD who were attending the Comprehensive Addiction Resources and Education Center, an outpatient psychiatry clinic located at New Jersey Medical School, from December 2019 to February 2020.

Of the 42 participants who initially consented, 39 completed the survey. The majority of the responders were Black (64.1%), had an annual income that was less than $20,000 (61.5%), and/or were unemployed or disabled (69.3%).

Most of the participants agreed or strongly agreed with the following statements:

• Scheduling appointments for SMAs is easy.
• I gain valuable information from the responses to other patients’ questions in SMAs.
• There is enough time for questions during SMAs.
• I gain valuable information from the doctor and social worker in SMAs.
• My medical needs are met during SMAs.
• I would recommend an SMA to other patients.
• Since starting SMAs, I find it easier to stick to my treatment plan.
• I have a lot of support outside of SMAs.
• People in SMAs give me the support I need to stick to my treatment plan.

Interestingly, despite the overall high satisfaction with SMAs, just 33% of participants said they preferred them to one-on-one visits, Dr. Akyar noted.

Further analyses showed that total satisfaction scores were positively associated with older age, being on disability, or being in retirement.
 

Bridging the gap

In a comment, Philip Wong, MD, New Jersey Medical School, Newark, noted that a more widespread use of SMAs could potentially bridge the treatment gap that currently exists in the United States.

“For providers, SMAs help reduce costs, improve productivity, prevent repeating of common advice, and increase outreach. These are all important at a time when the need for OUD treatment is increasing. This is especially true for places like Newark, which is one of the prime epicenters of the opioid epidemic,” said Dr. Wong.

Although he was not involved with this research, he and his colleagues recently conducted a literature review of publications relating to SMAs and found seven peer-reviewed articles. However, none was appropriately designed to compare SMAs with traditional one-on-one recovery treatment.

“We definitely need more clinical studies to further our understanding of SMAs as a tool for the medication-assisted treatment of opioid use disorder,” Dr. Wong said.

“There are currently a very limited number of physicians who can prescribe medication-assisted treatment in the first place. So, if that one provider can reach a larger community by doing these SMAs, then the potential is very great in terms of addressing the opioid epidemic,” he said.

David Kan, MD, chief medical officer of Bright Heart Health, San Ramon, Calif., agreed.

“SMAs are promising because they are efficient and allow more people to access treatment,” Dr. Kan said in an interview.

“Although the mechanism of SMA satisfaction is unclear, other research shows peer support and groups helpful for SUD treatment as a whole. SMA takes the best of many worlds and increases the potential number of patients treated for SUD,” he said.

Also asked to comment, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, said SMAs “are one of a number of important interventions that should be considered” in order to increase availability and access to medication providers for OUD.

However, more research is needed “to examine the impact on treatment uptake and patient and provider experiences,” said Dr. Lin.

Dr. Akyar, Dr. Wong, Dr. Kan, and Dr. Lin disclosed no relevant financial relationships.

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

Shared medical appointments (SMAs) are an acceptable way to receive treatment for opioid use disorder (OUD), new research suggests.

In a survey study, participants attending an urban outpatient buprenorphine clinic reported a high degree of satisfaction with SMAs. However, the majority also reported they preferred individual appointments.

Still, SMAs may serve a role in providing comprehensive care for certain subpopulations with OUD who are prone to isolation and may also increase capacity to treat more patients with a substance use disorder (SUD), said coinvestigator Serra Akyar, MD, Northwell Health Staten Island University Hospital, New York.

“By providing education and a forum for sharing, SMAs can lead to changes in behavior and enhance and reinforce coping and problem-solving skills,” Dr. Akyar said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

SMA vs. group therapy

SMA is not a form of group therapy, Dr. Akyar noted. Group therapy has a psychotherapy component and is led by a therapist. SMAs do not have a psychotherapeutic or a behavioral therapy component but provide education and an opportunity for sharing personal experiences of recovery.

“For example, the doctor participating in the group describes what happens in the brain to drive addiction and fellow participants share their personal anecdotes of recovery, including their struggles and successes,” Dr. Akyar said.

“While SMAs and group therapy seem similar, using the terms interchangeably would be incorrect given the differences in the type of care each group provides,” she added.

Recent research on SMAs for OUD is limited. Although previous studies have shown that the practice is highly acceptable and has comparable or better retention in care rates with buprenorphine versus individual appointments, these studies have been conducted in predominantly White populations and in suburban settings.

For the new study, the investigators wanted to examine how acceptable SMAs for OUD would be in an urban setting involving predominantly racial and ethnic minorities.

They administered a 15-minute survey to patients with OUD who were attending the Comprehensive Addiction Resources and Education Center, an outpatient psychiatry clinic located at New Jersey Medical School, from December 2019 to February 2020.

Of the 42 participants who initially consented, 39 completed the survey. The majority of the responders were Black (64.1%), had an annual income that was less than $20,000 (61.5%), and/or were unemployed or disabled (69.3%).

Most of the participants agreed or strongly agreed with the following statements:

• Scheduling appointments for SMAs is easy.
• I gain valuable information from the responses to other patients’ questions in SMAs.
• There is enough time for questions during SMAs.
• I gain valuable information from the doctor and social worker in SMAs.
• My medical needs are met during SMAs.
• I would recommend an SMA to other patients.
• Since starting SMAs, I find it easier to stick to my treatment plan.
• I have a lot of support outside of SMAs.
• People in SMAs give me the support I need to stick to my treatment plan.

Interestingly, despite the overall high satisfaction with SMAs, just 33% of participants said they preferred them to one-on-one visits, Dr. Akyar noted.

Further analyses showed that total satisfaction scores were positively associated with older age, being on disability, or being in retirement.
 

Bridging the gap

In a comment, Philip Wong, MD, New Jersey Medical School, Newark, noted that a more widespread use of SMAs could potentially bridge the treatment gap that currently exists in the United States.

“For providers, SMAs help reduce costs, improve productivity, prevent repeating of common advice, and increase outreach. These are all important at a time when the need for OUD treatment is increasing. This is especially true for places like Newark, which is one of the prime epicenters of the opioid epidemic,” said Dr. Wong.

Although he was not involved with this research, he and his colleagues recently conducted a literature review of publications relating to SMAs and found seven peer-reviewed articles. However, none was appropriately designed to compare SMAs with traditional one-on-one recovery treatment.

“We definitely need more clinical studies to further our understanding of SMAs as a tool for the medication-assisted treatment of opioid use disorder,” Dr. Wong said.

“There are currently a very limited number of physicians who can prescribe medication-assisted treatment in the first place. So, if that one provider can reach a larger community by doing these SMAs, then the potential is very great in terms of addressing the opioid epidemic,” he said.

David Kan, MD, chief medical officer of Bright Heart Health, San Ramon, Calif., agreed.

“SMAs are promising because they are efficient and allow more people to access treatment,” Dr. Kan said in an interview.

“Although the mechanism of SMA satisfaction is unclear, other research shows peer support and groups helpful for SUD treatment as a whole. SMA takes the best of many worlds and increases the potential number of patients treated for SUD,” he said.

Also asked to comment, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, said SMAs “are one of a number of important interventions that should be considered” in order to increase availability and access to medication providers for OUD.

However, more research is needed “to examine the impact on treatment uptake and patient and provider experiences,” said Dr. Lin.

Dr. Akyar, Dr. Wong, Dr. Kan, and Dr. Lin disclosed no relevant financial relationships.

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

Rare cancers comprise about 20% of all cancers in the United States and Europe, according to recent estimates, but patients with rare cancers are vastly underrepresented in clinical trials.

Recently, there has been a focus on immune checkpoint blockade (ICB) in common cancer types. Since several rare tumor types share similar biologic features with the more common tumors, there is a need to test ICB in rare tumors, particularly because remissions with ICB can be durable.

Enter the DART trial, a phase 2, single-arm study of combinatorial ICB with ipilimumab plus nivolumab in patients with unresectable or metastatic rare cancers.

Results from DART were recently presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting. Michael J. Wagner, MD, of the University of Washington, Seattle, reported results in patients with advanced or unresectable angiosarcoma, one of the rare tumor types included in DART.
 

About angiosarcomas

Angiosarcomas account for less than 3% of all adult soft-tissue sarcomas, according to a review published in The Lancet Oncology. Angiosarcomas may arise in any part of the body, especially the head and neck (27%), breast (19.7%), and extremities (15.3%). These cancers can be primary or secondary (i.e., associated with prior radiation therapy or chronic lymphedema).

Angiosarcomas are aggressive, difficult to treat, and confer high mortality. The tumors are responsive to chemotherapy, but responses are brief. The estimated 5-year survival rate for all patients with angiosarcoma, including those who present with localized disease, is 30%-40%.

According to Dr. Wagner, a subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and COSMIC signature 7, a DNA mutational signature that is consistent with other cancers caused by ultraviolet light exposure.

The high TMB subset of angiosarcomas is comparable with other cancer types that are responsive to ICB. Indeed, patients with angiosarcoma treated with ICB have shown responses, according to research published in the Journal for Immunotherapy of Cancer. However, no prospective studies of ICB in angiosarcoma have been published.
 

About DART

The DART trial includes more than 50 cohorts of rare cancer subtypes. Patients receive IV ipilimumab at 1 mg/kg every 6 weeks and IV nivolumab at 240 mg every 2 weeks.

The primary endpoint is objective response rate, as assessed by RECIST v1.1. Secondary endpoints include progression-free survival, overall survival, stable disease at 6 months, and toxicity.

The trial has a two-stage design. Six patients are enrolled in the first stage, and, if at least one patient responds to treatment, an additional 10 patients are enrolled in the second stage.

If at least two responses are seen among the 16 patients enrolled, further study of ICB is considered warranted.
 

Results in angiosarcoma

Dr. Wagner reported on the 16 angiosarcoma patients enrolled in DART. Nine patients had cutaneous primary tumors, seven had noncutaneous primary tumors, and three patients had radiation-associated angiosarcoma of the breast or chest wall.

Patients had received a median of two (range, zero to five) prior lines of therapy.

Adverse events (AEs) were consistent with prior safety results of the ipilimumab-nivolumab combination. Three-quarters of patients experienced an AE of any grade. The most common AEs were transaminase elevation, anemia, diarrhea, fatigue, hypothyroidism, pneumonitis, pruritus, and rash.

A quarter of patients had a grade 3-4 AE, and 12.5% of AEs led to premature treatment discontinuation. There were no fatal AEs.

The ORR was 25%. Responses occurred in 4 of the 16 patients, including 3 of 5 patients with primary cutaneous tumors of the scalp or face and 1 of 3 patients with radiation-associated breast angiosarcoma.

Two of the four responses and one case of stable disease have persisted for almost a year, and these patients remain on treatment. To put these results into perspective, Dr. Wagner noted that responses to cytotoxic chemotherapy rarely last 6 months.

The 6-month progression-free survival rate was 38%. The median overall survival has not yet been reached.

Dr. Wagner concluded that the combinatorial ICB regimen employed in DART was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site. Per the criteria of the DART trial, further investigation of ICB in angiosarcoma is warranted.
 

Molecular insights

Although correlative analyses of tumor tissue and peripheral blood are embedded in the DART trial, those analyses have not yet been performed. Eight of the 16 angiosarcoma patients had diagnostic molecular studies performed at their parent institutions, utilizing a variety of commercial platforms.

All eight patients for whom molecular data were available had at least two deleterious genomic alterations detected, but each had a distinct molecular profile.

Seven patients had TMB analyzed, including two partial responders to ICB. One of the seven patients had a high TMB, and this patient was one of the two responders. The other responder had an intermediate TMB.

Three patients had programmed death–ligand 1 staining on their tumors. Two of the three had high expression of PD-L1, including the responder with an intermediate TMB.
 

The real impact of DART

The DART trial is a “basket trial,” employing a similar treatment regimen for multiple tumor types. It provides a uniform framework for studying tumors that have been neglected in clinical trials heretofore.

Although the cohort of angiosarcoma patients is small, central pathology review was not required, and the treatment regimen was not compared directly with other potential therapies, the reported results of the ipilimumab-nivolumab regimen justify further study.

The biospecimens collected in DART will provide a rich source of data to identify common themes among responders and nonresponders, among patients who experience durable remissions and those who do not.

Angiosarcoma is not the only rare cancer for which combinatorial ICB has been valuable under the auspices of the DART trial. In Clinical Cancer Research, investigators reported an ORR of 44% among patients with high-grade neuroendocrine cancers, independent of primary site of origin. Progression-free survival at 6 months was 31%.

The DART trial is available at more than 800 sites, providing access to potentially promising treatment in a rigorous, scientifically valuable study for geographically underserved populations, including patients who live in rural areas.

The key message for practicing oncologists and clinical investigators is that clinical trials in rare tumors are feasible and can yield hope for patients who might lack it otherwise.

DART is funded by the National Cancer Institute and Bristol-Myers Squibb. Dr. Wagner disclosed relationships with Deciphera, Adaptimmune, GlaxoSmithKline, Athenex, and Incyte.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Wagner M et al. SITC 2020, Abstract 795.

Rare cancers comprise about 20% of all cancers in the United States and Europe, according to recent estimates, but patients with rare cancers are vastly underrepresented in clinical trials.

Recently, there has been a focus on immune checkpoint blockade (ICB) in common cancer types. Since several rare tumor types share similar biologic features with the more common tumors, there is a need to test ICB in rare tumors, particularly because remissions with ICB can be durable.

Enter the DART trial, a phase 2, single-arm study of combinatorial ICB with ipilimumab plus nivolumab in patients with unresectable or metastatic rare cancers.

Results from DART were recently presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting. Michael J. Wagner, MD, of the University of Washington, Seattle, reported results in patients with advanced or unresectable angiosarcoma, one of the rare tumor types included in DART.
 

About angiosarcomas

Angiosarcomas account for less than 3% of all adult soft-tissue sarcomas, according to a review published in The Lancet Oncology. Angiosarcomas may arise in any part of the body, especially the head and neck (27%), breast (19.7%), and extremities (15.3%). These cancers can be primary or secondary (i.e., associated with prior radiation therapy or chronic lymphedema).

Angiosarcomas are aggressive, difficult to treat, and confer high mortality. The tumors are responsive to chemotherapy, but responses are brief. The estimated 5-year survival rate for all patients with angiosarcoma, including those who present with localized disease, is 30%-40%.

According to Dr. Wagner, a subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and COSMIC signature 7, a DNA mutational signature that is consistent with other cancers caused by ultraviolet light exposure.

The high TMB subset of angiosarcomas is comparable with other cancer types that are responsive to ICB. Indeed, patients with angiosarcoma treated with ICB have shown responses, according to research published in the Journal for Immunotherapy of Cancer. However, no prospective studies of ICB in angiosarcoma have been published.
 

About DART

The DART trial includes more than 50 cohorts of rare cancer subtypes. Patients receive IV ipilimumab at 1 mg/kg every 6 weeks and IV nivolumab at 240 mg every 2 weeks.

The primary endpoint is objective response rate, as assessed by RECIST v1.1. Secondary endpoints include progression-free survival, overall survival, stable disease at 6 months, and toxicity.

The trial has a two-stage design. Six patients are enrolled in the first stage, and, if at least one patient responds to treatment, an additional 10 patients are enrolled in the second stage.

If at least two responses are seen among the 16 patients enrolled, further study of ICB is considered warranted.
 

Results in angiosarcoma

Dr. Wagner reported on the 16 angiosarcoma patients enrolled in DART. Nine patients had cutaneous primary tumors, seven had noncutaneous primary tumors, and three patients had radiation-associated angiosarcoma of the breast or chest wall.

Patients had received a median of two (range, zero to five) prior lines of therapy.

Adverse events (AEs) were consistent with prior safety results of the ipilimumab-nivolumab combination. Three-quarters of patients experienced an AE of any grade. The most common AEs were transaminase elevation, anemia, diarrhea, fatigue, hypothyroidism, pneumonitis, pruritus, and rash.

A quarter of patients had a grade 3-4 AE, and 12.5% of AEs led to premature treatment discontinuation. There were no fatal AEs.

The ORR was 25%. Responses occurred in 4 of the 16 patients, including 3 of 5 patients with primary cutaneous tumors of the scalp or face and 1 of 3 patients with radiation-associated breast angiosarcoma.

Two of the four responses and one case of stable disease have persisted for almost a year, and these patients remain on treatment. To put these results into perspective, Dr. Wagner noted that responses to cytotoxic chemotherapy rarely last 6 months.

The 6-month progression-free survival rate was 38%. The median overall survival has not yet been reached.

Dr. Wagner concluded that the combinatorial ICB regimen employed in DART was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site. Per the criteria of the DART trial, further investigation of ICB in angiosarcoma is warranted.
 

Molecular insights

Although correlative analyses of tumor tissue and peripheral blood are embedded in the DART trial, those analyses have not yet been performed. Eight of the 16 angiosarcoma patients had diagnostic molecular studies performed at their parent institutions, utilizing a variety of commercial platforms.

All eight patients for whom molecular data were available had at least two deleterious genomic alterations detected, but each had a distinct molecular profile.

Seven patients had TMB analyzed, including two partial responders to ICB. One of the seven patients had a high TMB, and this patient was one of the two responders. The other responder had an intermediate TMB.

Three patients had programmed death–ligand 1 staining on their tumors. Two of the three had high expression of PD-L1, including the responder with an intermediate TMB.
 

The real impact of DART

The DART trial is a “basket trial,” employing a similar treatment regimen for multiple tumor types. It provides a uniform framework for studying tumors that have been neglected in clinical trials heretofore.

Although the cohort of angiosarcoma patients is small, central pathology review was not required, and the treatment regimen was not compared directly with other potential therapies, the reported results of the ipilimumab-nivolumab regimen justify further study.

The biospecimens collected in DART will provide a rich source of data to identify common themes among responders and nonresponders, among patients who experience durable remissions and those who do not.

Angiosarcoma is not the only rare cancer for which combinatorial ICB has been valuable under the auspices of the DART trial. In Clinical Cancer Research, investigators reported an ORR of 44% among patients with high-grade neuroendocrine cancers, independent of primary site of origin. Progression-free survival at 6 months was 31%.

The DART trial is available at more than 800 sites, providing access to potentially promising treatment in a rigorous, scientifically valuable study for geographically underserved populations, including patients who live in rural areas.

The key message for practicing oncologists and clinical investigators is that clinical trials in rare tumors are feasible and can yield hope for patients who might lack it otherwise.

DART is funded by the National Cancer Institute and Bristol-Myers Squibb. Dr. Wagner disclosed relationships with Deciphera, Adaptimmune, GlaxoSmithKline, Athenex, and Incyte.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Wagner M et al. SITC 2020, Abstract 795.

Rare cancers comprise about 20% of all cancers in the United States and Europe, according to recent estimates, but patients with rare cancers are vastly underrepresented in clinical trials.

Recently, there has been a focus on immune checkpoint blockade (ICB) in common cancer types. Since several rare tumor types share similar biologic features with the more common tumors, there is a need to test ICB in rare tumors, particularly because remissions with ICB can be durable.

Enter the DART trial, a phase 2, single-arm study of combinatorial ICB with ipilimumab plus nivolumab in patients with unresectable or metastatic rare cancers.

Results from DART were recently presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting. Michael J. Wagner, MD, of the University of Washington, Seattle, reported results in patients with advanced or unresectable angiosarcoma, one of the rare tumor types included in DART.
 

About angiosarcomas

Angiosarcomas account for less than 3% of all adult soft-tissue sarcomas, according to a review published in The Lancet Oncology. Angiosarcomas may arise in any part of the body, especially the head and neck (27%), breast (19.7%), and extremities (15.3%). These cancers can be primary or secondary (i.e., associated with prior radiation therapy or chronic lymphedema).

Angiosarcomas are aggressive, difficult to treat, and confer high mortality. The tumors are responsive to chemotherapy, but responses are brief. The estimated 5-year survival rate for all patients with angiosarcoma, including those who present with localized disease, is 30%-40%.

According to Dr. Wagner, a subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and COSMIC signature 7, a DNA mutational signature that is consistent with other cancers caused by ultraviolet light exposure.

The high TMB subset of angiosarcomas is comparable with other cancer types that are responsive to ICB. Indeed, patients with angiosarcoma treated with ICB have shown responses, according to research published in the Journal for Immunotherapy of Cancer. However, no prospective studies of ICB in angiosarcoma have been published.
 

About DART

The DART trial includes more than 50 cohorts of rare cancer subtypes. Patients receive IV ipilimumab at 1 mg/kg every 6 weeks and IV nivolumab at 240 mg every 2 weeks.

The primary endpoint is objective response rate, as assessed by RECIST v1.1. Secondary endpoints include progression-free survival, overall survival, stable disease at 6 months, and toxicity.

The trial has a two-stage design. Six patients are enrolled in the first stage, and, if at least one patient responds to treatment, an additional 10 patients are enrolled in the second stage.

If at least two responses are seen among the 16 patients enrolled, further study of ICB is considered warranted.
 

Results in angiosarcoma

Dr. Wagner reported on the 16 angiosarcoma patients enrolled in DART. Nine patients had cutaneous primary tumors, seven had noncutaneous primary tumors, and three patients had radiation-associated angiosarcoma of the breast or chest wall.

Patients had received a median of two (range, zero to five) prior lines of therapy.

Adverse events (AEs) were consistent with prior safety results of the ipilimumab-nivolumab combination. Three-quarters of patients experienced an AE of any grade. The most common AEs were transaminase elevation, anemia, diarrhea, fatigue, hypothyroidism, pneumonitis, pruritus, and rash.

A quarter of patients had a grade 3-4 AE, and 12.5% of AEs led to premature treatment discontinuation. There were no fatal AEs.

The ORR was 25%. Responses occurred in 4 of the 16 patients, including 3 of 5 patients with primary cutaneous tumors of the scalp or face and 1 of 3 patients with radiation-associated breast angiosarcoma.

Two of the four responses and one case of stable disease have persisted for almost a year, and these patients remain on treatment. To put these results into perspective, Dr. Wagner noted that responses to cytotoxic chemotherapy rarely last 6 months.

The 6-month progression-free survival rate was 38%. The median overall survival has not yet been reached.

Dr. Wagner concluded that the combinatorial ICB regimen employed in DART was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site. Per the criteria of the DART trial, further investigation of ICB in angiosarcoma is warranted.
 

Molecular insights

Although correlative analyses of tumor tissue and peripheral blood are embedded in the DART trial, those analyses have not yet been performed. Eight of the 16 angiosarcoma patients had diagnostic molecular studies performed at their parent institutions, utilizing a variety of commercial platforms.

All eight patients for whom molecular data were available had at least two deleterious genomic alterations detected, but each had a distinct molecular profile.

Seven patients had TMB analyzed, including two partial responders to ICB. One of the seven patients had a high TMB, and this patient was one of the two responders. The other responder had an intermediate TMB.

Three patients had programmed death–ligand 1 staining on their tumors. Two of the three had high expression of PD-L1, including the responder with an intermediate TMB.
 

The real impact of DART

The DART trial is a “basket trial,” employing a similar treatment regimen for multiple tumor types. It provides a uniform framework for studying tumors that have been neglected in clinical trials heretofore.

Although the cohort of angiosarcoma patients is small, central pathology review was not required, and the treatment regimen was not compared directly with other potential therapies, the reported results of the ipilimumab-nivolumab regimen justify further study.

The biospecimens collected in DART will provide a rich source of data to identify common themes among responders and nonresponders, among patients who experience durable remissions and those who do not.

Angiosarcoma is not the only rare cancer for which combinatorial ICB has been valuable under the auspices of the DART trial. In Clinical Cancer Research, investigators reported an ORR of 44% among patients with high-grade neuroendocrine cancers, independent of primary site of origin. Progression-free survival at 6 months was 31%.

The DART trial is available at more than 800 sites, providing access to potentially promising treatment in a rigorous, scientifically valuable study for geographically underserved populations, including patients who live in rural areas.

The key message for practicing oncologists and clinical investigators is that clinical trials in rare tumors are feasible and can yield hope for patients who might lack it otherwise.

DART is funded by the National Cancer Institute and Bristol-Myers Squibb. Dr. Wagner disclosed relationships with Deciphera, Adaptimmune, GlaxoSmithKline, Athenex, and Incyte.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Wagner M et al. SITC 2020, Abstract 795.