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COVID plus MI confers poor prognosis; 1 in 3 die in hospital
COVID-19 patients with ST-segment elevation MI (STEMI) represent a population with unique demographic and clinical features resulting in a high risk for mortality, according to initial findings from the North American Cardiovascular COVID-19 Myocardial Infarction (NACMI) Registry.
“This is the largest registry of COVID-positive patients presenting with STEMI [and] the results clearly illustrate the challenges and uniqueness of this patient population that deserves prompt and special attention,” study cochair Timothy Henry, MD, president-elect of the Society for Cardiovascular Angiography & Interventions, said in a news release.
The NACMI registry is a collaborative effort between the SCAI, the American College of Cardiology Interventional Council, and the Canadian Association of Interventional Cardiology.
“The rapid development of this ongoing, critically important prospective registry reflects the strong and unique collaboration of all three societies. It was gratifying to be part of this process and hopefully the results will improve the care of our patients and stimulate further research,” Dr. Henry said in the news release.
The registry has enrolled 1,185 patients presenting with STEMI at 64 sites across the United States and Canada. Participants include 230 COVID-positive STEMI patients; 495 STEMI patients suspected but ultimately confirmed not to have COVID-19; and 460 age-and sex-matched control STEMI patients treated prior to the pandemic who are part of the Midwest STEMI Consortium.
The initial findings from the registry were published online in the Journal of the American College of Cardiology.
Atypical symptoms may explain high death rate
The primary outcome – a composite of in-hospital death, stroke, recurrent MI, or repeat unplanned revascularization – occurred in 36% of COVID-positive patients, compared with 13% of COVID-negative patients and 5% of control patients (P < .001 relative to controls).
This difference was driven largely by a “very high” in-hospital death rate in COVID-positive patients, lead author Santiago Garcia, MD, Minneapolis Heart Institute Foundation, said in an interview.
The in-hospital death rate was 33% in COVID-positive patients, compared with 11% in COVID-negative patients and 4% in controls. Stroke also occurred more often in COVID-positive patients at 3% versus 2% in COVID-negative and 0% in controls.
These initial findings suggest that the combination of STEMI and COVID-19 infection “confers a poor prognosis, with one in three patients succumbing to the disease, even among patients selected for invasive angiography (28% mortality),” the investigators wrote.
The data also show that STEMI in COVID-positive patients disproportionately affects ethnic minorities (23% Hispanic and 24% Black) with diabetes, which was present in 46% of COVID-positive patients.
COVID-positive patients with STEMI are more likely to present with atypical symptoms such as dyspnea (54%), pulmonary infiltrates on chest x-ray (46%), and high-risk conditions such as cardiogenic shock (18%), “which may explain the high fatality rate,” Dr. Garcia said.
Despite these high-risk features, COVID-positive patients are less apt to undergo invasive angiography when compared with COVID-negative and control STEMI patients (78% vs. 96% vs. 100%).
The majority of patients (71%) who did under angiography received primary percutaneous coronary intervention (PPCI) with very small treatment delays (at 15 minutes) during the pandemic.
Another notable finding is that “many patients (23%) have ‘no culprit’ vessel and may represent different etiologies of ST-segment elevation including microemboli, myocarditis, Takotsubo cardiomyopathy,” Dr. Garcia said in an interview.
“In line with current guidelines, patients with suspected STEMI should be managed with PPCI, without delay while the safety of health care providers is ensured,” Ran Kornowski, MD, and Katia Orvin, MD, both with Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, wrote in a linked editorial.
“In this case, PPCI should be performed routinely, even if the patient is presumed to have COVID-19, because PPCI should not be postponed. Confirmation of SARS-CoV-2 infection should not delay urgent decision management concerning reperfusion strategy,” they advised.
Looking ahead, Garcia said plans for the registry include determining predictors of in-hospital mortality and studying demographic and treatment trends as the pandemic continues with more virulent strains of the virus.
Various subgroup analyses are also planned as well as an independent angiographic and electrocardiographic core lab analysis. A comparative analysis of data from the US and Canada is also planned.
This work was supported by an ACC Accreditation Grant, Saskatchewan Health Research Foundation, and grants from Medtronic and Abbott Vascular to SCAI. Dr. Garcia has received institutional research grants from Edwards Lifesciences, BSCI, Medtronic, and Abbott Vascular; has served as a consultant for Medtronic and BSCI; and has served as a proctor for Edwards Lifesciences. Dr. Kornowski and Dr. Orvin disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 patients with ST-segment elevation MI (STEMI) represent a population with unique demographic and clinical features resulting in a high risk for mortality, according to initial findings from the North American Cardiovascular COVID-19 Myocardial Infarction (NACMI) Registry.
“This is the largest registry of COVID-positive patients presenting with STEMI [and] the results clearly illustrate the challenges and uniqueness of this patient population that deserves prompt and special attention,” study cochair Timothy Henry, MD, president-elect of the Society for Cardiovascular Angiography & Interventions, said in a news release.
The NACMI registry is a collaborative effort between the SCAI, the American College of Cardiology Interventional Council, and the Canadian Association of Interventional Cardiology.
“The rapid development of this ongoing, critically important prospective registry reflects the strong and unique collaboration of all three societies. It was gratifying to be part of this process and hopefully the results will improve the care of our patients and stimulate further research,” Dr. Henry said in the news release.
The registry has enrolled 1,185 patients presenting with STEMI at 64 sites across the United States and Canada. Participants include 230 COVID-positive STEMI patients; 495 STEMI patients suspected but ultimately confirmed not to have COVID-19; and 460 age-and sex-matched control STEMI patients treated prior to the pandemic who are part of the Midwest STEMI Consortium.
The initial findings from the registry were published online in the Journal of the American College of Cardiology.
Atypical symptoms may explain high death rate
The primary outcome – a composite of in-hospital death, stroke, recurrent MI, or repeat unplanned revascularization – occurred in 36% of COVID-positive patients, compared with 13% of COVID-negative patients and 5% of control patients (P < .001 relative to controls).
This difference was driven largely by a “very high” in-hospital death rate in COVID-positive patients, lead author Santiago Garcia, MD, Minneapolis Heart Institute Foundation, said in an interview.
The in-hospital death rate was 33% in COVID-positive patients, compared with 11% in COVID-negative patients and 4% in controls. Stroke also occurred more often in COVID-positive patients at 3% versus 2% in COVID-negative and 0% in controls.
These initial findings suggest that the combination of STEMI and COVID-19 infection “confers a poor prognosis, with one in three patients succumbing to the disease, even among patients selected for invasive angiography (28% mortality),” the investigators wrote.
The data also show that STEMI in COVID-positive patients disproportionately affects ethnic minorities (23% Hispanic and 24% Black) with diabetes, which was present in 46% of COVID-positive patients.
COVID-positive patients with STEMI are more likely to present with atypical symptoms such as dyspnea (54%), pulmonary infiltrates on chest x-ray (46%), and high-risk conditions such as cardiogenic shock (18%), “which may explain the high fatality rate,” Dr. Garcia said.
Despite these high-risk features, COVID-positive patients are less apt to undergo invasive angiography when compared with COVID-negative and control STEMI patients (78% vs. 96% vs. 100%).
The majority of patients (71%) who did under angiography received primary percutaneous coronary intervention (PPCI) with very small treatment delays (at 15 minutes) during the pandemic.
Another notable finding is that “many patients (23%) have ‘no culprit’ vessel and may represent different etiologies of ST-segment elevation including microemboli, myocarditis, Takotsubo cardiomyopathy,” Dr. Garcia said in an interview.
“In line with current guidelines, patients with suspected STEMI should be managed with PPCI, without delay while the safety of health care providers is ensured,” Ran Kornowski, MD, and Katia Orvin, MD, both with Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, wrote in a linked editorial.
“In this case, PPCI should be performed routinely, even if the patient is presumed to have COVID-19, because PPCI should not be postponed. Confirmation of SARS-CoV-2 infection should not delay urgent decision management concerning reperfusion strategy,” they advised.
Looking ahead, Garcia said plans for the registry include determining predictors of in-hospital mortality and studying demographic and treatment trends as the pandemic continues with more virulent strains of the virus.
Various subgroup analyses are also planned as well as an independent angiographic and electrocardiographic core lab analysis. A comparative analysis of data from the US and Canada is also planned.
This work was supported by an ACC Accreditation Grant, Saskatchewan Health Research Foundation, and grants from Medtronic and Abbott Vascular to SCAI. Dr. Garcia has received institutional research grants from Edwards Lifesciences, BSCI, Medtronic, and Abbott Vascular; has served as a consultant for Medtronic and BSCI; and has served as a proctor for Edwards Lifesciences. Dr. Kornowski and Dr. Orvin disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 patients with ST-segment elevation MI (STEMI) represent a population with unique demographic and clinical features resulting in a high risk for mortality, according to initial findings from the North American Cardiovascular COVID-19 Myocardial Infarction (NACMI) Registry.
“This is the largest registry of COVID-positive patients presenting with STEMI [and] the results clearly illustrate the challenges and uniqueness of this patient population that deserves prompt and special attention,” study cochair Timothy Henry, MD, president-elect of the Society for Cardiovascular Angiography & Interventions, said in a news release.
The NACMI registry is a collaborative effort between the SCAI, the American College of Cardiology Interventional Council, and the Canadian Association of Interventional Cardiology.
“The rapid development of this ongoing, critically important prospective registry reflects the strong and unique collaboration of all three societies. It was gratifying to be part of this process and hopefully the results will improve the care of our patients and stimulate further research,” Dr. Henry said in the news release.
The registry has enrolled 1,185 patients presenting with STEMI at 64 sites across the United States and Canada. Participants include 230 COVID-positive STEMI patients; 495 STEMI patients suspected but ultimately confirmed not to have COVID-19; and 460 age-and sex-matched control STEMI patients treated prior to the pandemic who are part of the Midwest STEMI Consortium.
The initial findings from the registry were published online in the Journal of the American College of Cardiology.
Atypical symptoms may explain high death rate
The primary outcome – a composite of in-hospital death, stroke, recurrent MI, or repeat unplanned revascularization – occurred in 36% of COVID-positive patients, compared with 13% of COVID-negative patients and 5% of control patients (P < .001 relative to controls).
This difference was driven largely by a “very high” in-hospital death rate in COVID-positive patients, lead author Santiago Garcia, MD, Minneapolis Heart Institute Foundation, said in an interview.
The in-hospital death rate was 33% in COVID-positive patients, compared with 11% in COVID-negative patients and 4% in controls. Stroke also occurred more often in COVID-positive patients at 3% versus 2% in COVID-negative and 0% in controls.
These initial findings suggest that the combination of STEMI and COVID-19 infection “confers a poor prognosis, with one in three patients succumbing to the disease, even among patients selected for invasive angiography (28% mortality),” the investigators wrote.
The data also show that STEMI in COVID-positive patients disproportionately affects ethnic minorities (23% Hispanic and 24% Black) with diabetes, which was present in 46% of COVID-positive patients.
COVID-positive patients with STEMI are more likely to present with atypical symptoms such as dyspnea (54%), pulmonary infiltrates on chest x-ray (46%), and high-risk conditions such as cardiogenic shock (18%), “which may explain the high fatality rate,” Dr. Garcia said.
Despite these high-risk features, COVID-positive patients are less apt to undergo invasive angiography when compared with COVID-negative and control STEMI patients (78% vs. 96% vs. 100%).
The majority of patients (71%) who did under angiography received primary percutaneous coronary intervention (PPCI) with very small treatment delays (at 15 minutes) during the pandemic.
Another notable finding is that “many patients (23%) have ‘no culprit’ vessel and may represent different etiologies of ST-segment elevation including microemboli, myocarditis, Takotsubo cardiomyopathy,” Dr. Garcia said in an interview.
“In line with current guidelines, patients with suspected STEMI should be managed with PPCI, without delay while the safety of health care providers is ensured,” Ran Kornowski, MD, and Katia Orvin, MD, both with Rabin Medical Center, Petah Tikva, Israel, and Tel Aviv University, wrote in a linked editorial.
“In this case, PPCI should be performed routinely, even if the patient is presumed to have COVID-19, because PPCI should not be postponed. Confirmation of SARS-CoV-2 infection should not delay urgent decision management concerning reperfusion strategy,” they advised.
Looking ahead, Garcia said plans for the registry include determining predictors of in-hospital mortality and studying demographic and treatment trends as the pandemic continues with more virulent strains of the virus.
Various subgroup analyses are also planned as well as an independent angiographic and electrocardiographic core lab analysis. A comparative analysis of data from the US and Canada is also planned.
This work was supported by an ACC Accreditation Grant, Saskatchewan Health Research Foundation, and grants from Medtronic and Abbott Vascular to SCAI. Dr. Garcia has received institutional research grants from Edwards Lifesciences, BSCI, Medtronic, and Abbott Vascular; has served as a consultant for Medtronic and BSCI; and has served as a proctor for Edwards Lifesciences. Dr. Kornowski and Dr. Orvin disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cushing’s death rate ‘unacceptable,’ triple that of general population
Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.
Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.
Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.
“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.
Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”
She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”
Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”
“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.
In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”
Largest study in scale and scope of Cushing’s syndrome mortality
Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.
Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.
“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.
The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).
Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).
This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).
The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).
The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.
Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).
Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).
Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).
Preventing perioperative mortality: Consider thromboprophylaxis
Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”
Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.
The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.
“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.
A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.
Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”
Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.
A version of this article first appeared on Medscape.com.
Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.
Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.
Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.
“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.
Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”
She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”
Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”
“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.
In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”
Largest study in scale and scope of Cushing’s syndrome mortality
Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.
Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.
“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.
The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).
Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).
This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).
The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).
The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.
Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).
Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).
Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).
Preventing perioperative mortality: Consider thromboprophylaxis
Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”
Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.
The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.
“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.
A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.
Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”
Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.
A version of this article first appeared on Medscape.com.
Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.
Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.
Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.
“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.
Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”
She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”
Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”
“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.
In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”
Largest study in scale and scope of Cushing’s syndrome mortality
Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.
Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.
“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.
The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).
Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).
This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).
The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).
The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.
Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).
Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).
Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).
Preventing perioperative mortality: Consider thromboprophylaxis
Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”
Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.
The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.
“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.
A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.
Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”
Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.
A version of this article first appeared on Medscape.com.
Frontline brentuximab vedotin shows promise in high-risk pediatric Hodgkin lymphoma
A frontline treatment regimen including brentuximab vedotin (Bv) was well tolerated, was highly effective, and significantly reduced radiation exposure in pediatric patients with high-risk Hodgkin lymphoma, according to the results of an open-label, phase 2 trial.
Of 77 patients enrolled in the investigator-initiated, single-arm, multicenter trial, 27 (35%) achieved complete remission (CR) without radiation at the early response assessment (ERA) after two cycles of therapy, reported Monika L. Metzger, MD, of St. Jude Children’s Research Hospital, Memphis, Tenn. and colleagues. The report was published online in the Journal of Clinical Oncology.
The addition of Bv also resulted in superior event-free survival (97.4%) and overall survival (98.7%) at median follow-up of 3.4 years, compared with previously published pediatric trials, such as the HOD99 trial (EFS and OS of 80.8% and 96.5%, respectively), the authors noted.
Bv chemotherapy
Bv, a targeted anti-CD30 antibody-drug conjugate, received expanded Food and Drug Administration approval in March 2018 for frontline use in combination with chemotherapy in adults with stage III or IV classical Hodgkin lymphoma (HL). The current study is the first to include Bv as part of a chemotherapy regimen in the frontline setting for pediatric classical HL, the authors noted, adding that their primary aim was to reduce prescribed radiation thereby limiting late toxicities associated with radiation in this population.
Patients enrolled were children and adolescents aged 18 years and under with stage IIB, IIIB, or IV classical HL. Bv was used in place of vincristine in the standard OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) frontline regimen for pediatric HL.
The Bv-based chemotherapy regimen was well tolerated and mostly limited to low-grade nausea, vomiting, and constipation, and the most common adverse events were hematologic events occurring mainly during the first two cycles of chemotherapy.
“Notably, we observed a very low incidence of neuropathy (4%) by both clinician and patient report, and no participants required Bv dose reduction or discontinuation,” they wrote, explaining that neuropathy is more common with vincristine.
Radiation exposure
Residual node radiotherapy (RNRT) was delivered at a prescribed dose of 25.5 Gy in 17 fractions of 1.5 Gy, 2-4 weeks after completion of chemotherapy only to nodal sites that did not achieve a CR at the early response assessment (ERA) after two cycles of therapy.
“Patients treated with RNRT had significantly lower integral radiation dose compared with patients treated on HOD99 with [involved-field radiation therapy] (78.1 J vs. 249.6 J),” the authors wrote. “Doses to specific organs were also compared ... [t]he mean heart dose was reduced to 5.29 Gy from 16.9 Gy, and the mean thyroid dose was reduced to 4.46 Gy from 25.9 Gy.”
Women also had significantly less breast radiation exposure (mean of 3.21 Gy vs. 6.85 Gy in HOD99).
One irradiated patient experienced disease progression at the end of therapy, but remained disease free more than 6 years following salvage therapy, and one unexpected death occurred, the authors said.
“We have already reduced the use of radiation for low-risk Hodgkin lymphoma patients. In this study we’ve shown that it is also possible to either omit or reduce the extent of radiation for high-risk patients, using highly focal methods such as proton beam radiation or intensity modulated radiation,” co–senior author Matthew Krasin, MD, of St. Jude’s department of radiation oncology, stated in a press release.
Next steps
Co–senior author Melissa Hudson, MD, the St. Jude cancer survivorship division director, added that “[b]eing able to offer Hodgkin lymphoma patients a targeted therapy in the frontline setting is an exciting development.
“The favorable safety and toxicity profile of Bv in combination with chemotherapy for high-risk pediatric patients supports its prospective evaluation in a randomized trial,” the authors concluded, noting that “[l]onger follow-up is required to establish if this approach reduces risk of late-occurring toxicities such as second malignant neoplasms in this cohort of minimally irradiated patients.”
The study was sponsored by Seattle Genetics. The research at St. Jude was funded in part by grants from the National Cancer Institute and ALSAC (American Lebanese Syrian Associated Charities), St. Jude’s fundraising and awareness organization. Dr. Metzger reported research funding from Seattle Genetics. Dr. Krasin reported a consulting or advisory role for Debiopharm Group. Dr. Hudson reported a consulting or advisory role for Oncology Research Information Exchange Network, Princess Máxima Center.
A frontline treatment regimen including brentuximab vedotin (Bv) was well tolerated, was highly effective, and significantly reduced radiation exposure in pediatric patients with high-risk Hodgkin lymphoma, according to the results of an open-label, phase 2 trial.
Of 77 patients enrolled in the investigator-initiated, single-arm, multicenter trial, 27 (35%) achieved complete remission (CR) without radiation at the early response assessment (ERA) after two cycles of therapy, reported Monika L. Metzger, MD, of St. Jude Children’s Research Hospital, Memphis, Tenn. and colleagues. The report was published online in the Journal of Clinical Oncology.
The addition of Bv also resulted in superior event-free survival (97.4%) and overall survival (98.7%) at median follow-up of 3.4 years, compared with previously published pediatric trials, such as the HOD99 trial (EFS and OS of 80.8% and 96.5%, respectively), the authors noted.
Bv chemotherapy
Bv, a targeted anti-CD30 antibody-drug conjugate, received expanded Food and Drug Administration approval in March 2018 for frontline use in combination with chemotherapy in adults with stage III or IV classical Hodgkin lymphoma (HL). The current study is the first to include Bv as part of a chemotherapy regimen in the frontline setting for pediatric classical HL, the authors noted, adding that their primary aim was to reduce prescribed radiation thereby limiting late toxicities associated with radiation in this population.
Patients enrolled were children and adolescents aged 18 years and under with stage IIB, IIIB, or IV classical HL. Bv was used in place of vincristine in the standard OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) frontline regimen for pediatric HL.
The Bv-based chemotherapy regimen was well tolerated and mostly limited to low-grade nausea, vomiting, and constipation, and the most common adverse events were hematologic events occurring mainly during the first two cycles of chemotherapy.
“Notably, we observed a very low incidence of neuropathy (4%) by both clinician and patient report, and no participants required Bv dose reduction or discontinuation,” they wrote, explaining that neuropathy is more common with vincristine.
Radiation exposure
Residual node radiotherapy (RNRT) was delivered at a prescribed dose of 25.5 Gy in 17 fractions of 1.5 Gy, 2-4 weeks after completion of chemotherapy only to nodal sites that did not achieve a CR at the early response assessment (ERA) after two cycles of therapy.
“Patients treated with RNRT had significantly lower integral radiation dose compared with patients treated on HOD99 with [involved-field radiation therapy] (78.1 J vs. 249.6 J),” the authors wrote. “Doses to specific organs were also compared ... [t]he mean heart dose was reduced to 5.29 Gy from 16.9 Gy, and the mean thyroid dose was reduced to 4.46 Gy from 25.9 Gy.”
Women also had significantly less breast radiation exposure (mean of 3.21 Gy vs. 6.85 Gy in HOD99).
One irradiated patient experienced disease progression at the end of therapy, but remained disease free more than 6 years following salvage therapy, and one unexpected death occurred, the authors said.
“We have already reduced the use of radiation for low-risk Hodgkin lymphoma patients. In this study we’ve shown that it is also possible to either omit or reduce the extent of radiation for high-risk patients, using highly focal methods such as proton beam radiation or intensity modulated radiation,” co–senior author Matthew Krasin, MD, of St. Jude’s department of radiation oncology, stated in a press release.
Next steps
Co–senior author Melissa Hudson, MD, the St. Jude cancer survivorship division director, added that “[b]eing able to offer Hodgkin lymphoma patients a targeted therapy in the frontline setting is an exciting development.
“The favorable safety and toxicity profile of Bv in combination with chemotherapy for high-risk pediatric patients supports its prospective evaluation in a randomized trial,” the authors concluded, noting that “[l]onger follow-up is required to establish if this approach reduces risk of late-occurring toxicities such as second malignant neoplasms in this cohort of minimally irradiated patients.”
The study was sponsored by Seattle Genetics. The research at St. Jude was funded in part by grants from the National Cancer Institute and ALSAC (American Lebanese Syrian Associated Charities), St. Jude’s fundraising and awareness organization. Dr. Metzger reported research funding from Seattle Genetics. Dr. Krasin reported a consulting or advisory role for Debiopharm Group. Dr. Hudson reported a consulting or advisory role for Oncology Research Information Exchange Network, Princess Máxima Center.
A frontline treatment regimen including brentuximab vedotin (Bv) was well tolerated, was highly effective, and significantly reduced radiation exposure in pediatric patients with high-risk Hodgkin lymphoma, according to the results of an open-label, phase 2 trial.
Of 77 patients enrolled in the investigator-initiated, single-arm, multicenter trial, 27 (35%) achieved complete remission (CR) without radiation at the early response assessment (ERA) after two cycles of therapy, reported Monika L. Metzger, MD, of St. Jude Children’s Research Hospital, Memphis, Tenn. and colleagues. The report was published online in the Journal of Clinical Oncology.
The addition of Bv also resulted in superior event-free survival (97.4%) and overall survival (98.7%) at median follow-up of 3.4 years, compared with previously published pediatric trials, such as the HOD99 trial (EFS and OS of 80.8% and 96.5%, respectively), the authors noted.
Bv chemotherapy
Bv, a targeted anti-CD30 antibody-drug conjugate, received expanded Food and Drug Administration approval in March 2018 for frontline use in combination with chemotherapy in adults with stage III or IV classical Hodgkin lymphoma (HL). The current study is the first to include Bv as part of a chemotherapy regimen in the frontline setting for pediatric classical HL, the authors noted, adding that their primary aim was to reduce prescribed radiation thereby limiting late toxicities associated with radiation in this population.
Patients enrolled were children and adolescents aged 18 years and under with stage IIB, IIIB, or IV classical HL. Bv was used in place of vincristine in the standard OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) frontline regimen for pediatric HL.
The Bv-based chemotherapy regimen was well tolerated and mostly limited to low-grade nausea, vomiting, and constipation, and the most common adverse events were hematologic events occurring mainly during the first two cycles of chemotherapy.
“Notably, we observed a very low incidence of neuropathy (4%) by both clinician and patient report, and no participants required Bv dose reduction or discontinuation,” they wrote, explaining that neuropathy is more common with vincristine.
Radiation exposure
Residual node radiotherapy (RNRT) was delivered at a prescribed dose of 25.5 Gy in 17 fractions of 1.5 Gy, 2-4 weeks after completion of chemotherapy only to nodal sites that did not achieve a CR at the early response assessment (ERA) after two cycles of therapy.
“Patients treated with RNRT had significantly lower integral radiation dose compared with patients treated on HOD99 with [involved-field radiation therapy] (78.1 J vs. 249.6 J),” the authors wrote. “Doses to specific organs were also compared ... [t]he mean heart dose was reduced to 5.29 Gy from 16.9 Gy, and the mean thyroid dose was reduced to 4.46 Gy from 25.9 Gy.”
Women also had significantly less breast radiation exposure (mean of 3.21 Gy vs. 6.85 Gy in HOD99).
One irradiated patient experienced disease progression at the end of therapy, but remained disease free more than 6 years following salvage therapy, and one unexpected death occurred, the authors said.
“We have already reduced the use of radiation for low-risk Hodgkin lymphoma patients. In this study we’ve shown that it is also possible to either omit or reduce the extent of radiation for high-risk patients, using highly focal methods such as proton beam radiation or intensity modulated radiation,” co–senior author Matthew Krasin, MD, of St. Jude’s department of radiation oncology, stated in a press release.
Next steps
Co–senior author Melissa Hudson, MD, the St. Jude cancer survivorship division director, added that “[b]eing able to offer Hodgkin lymphoma patients a targeted therapy in the frontline setting is an exciting development.
“The favorable safety and toxicity profile of Bv in combination with chemotherapy for high-risk pediatric patients supports its prospective evaluation in a randomized trial,” the authors concluded, noting that “[l]onger follow-up is required to establish if this approach reduces risk of late-occurring toxicities such as second malignant neoplasms in this cohort of minimally irradiated patients.”
The study was sponsored by Seattle Genetics. The research at St. Jude was funded in part by grants from the National Cancer Institute and ALSAC (American Lebanese Syrian Associated Charities), St. Jude’s fundraising and awareness organization. Dr. Metzger reported research funding from Seattle Genetics. Dr. Krasin reported a consulting or advisory role for Debiopharm Group. Dr. Hudson reported a consulting or advisory role for Oncology Research Information Exchange Network, Princess Máxima Center.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
GENUINE improvements: Ublituximab plus ibrutinib for CLL
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease associated with several known genetic abnormalities, including 17p deletion (del[17p]), 11q deletion (del[11q]), and TP53 gene mutations, which are adverse prognostic markers among patients treated with chemoimmunotherapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is approved for patients with untreated, relapsed, or refractory disease, including those with del(17p). Clinicians will soon have the chance to pair it with ublituximab, a next-generation, glycoengineered, type I, anti-CD20 monoclonal antibody that binds to a unique epitope on CD20, differentiating it from rituximab, ofatumumab, and obinutuzumab. Results from the phase 3 GENUINE trial, which were recently published in The Lancet Haematology, showed that ublituximab plus ibrutinib was superior to ibrutinib alone for patients with relapsed or refractory high-risk CLL.
This news organization spoke with Jennifer R. Brown, MD, PhD, director of the CLL Center and institute physician at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston, about the GENUINE trial and its potential impact on treatment choices going forward.
What type of patients were treated in the GENUINE trial?
Dr. Brown: This is a trial among relapsed/refractory CLL patients with 17p or 11q deletion or TP53 mutation. Patients aged 18 years or older with CLL who warranted treatment, as defined by International Workshop on CLL criteria, were eligible if they had previously received at least two cycles of at least one standard treatment regimen, had an Eastern Cooperative Oncology Group performance status of 2 or lower, and had high-risk cytogenetics, defined as the presence of at least one of del(17p), del(11q), or TP53 mutation confirmed by a central laboratory with fluorescence in situ hybridization and/or next-generation sequencing.
What were the main outcomes of the trial?
Originally, the GENUINE trial had coprimary endpoints of progression-free survival (PFS) and overall response rate. Because of slow accrual, it was amended to have one primary endpoint of independent review committee (IRC)–assessed ORR.
IRC-assessed ORR was improved from 65% to 83% with the addition of ublituximab. PFS also improved significantly in the ublituximab group, with an even greater improvement when the analysis was limited to those with del(17p) or TP53 aberrancy, but this outcome was limited by the reduced sample size of the study as well as the relatively short PFS of the ibrutinib arm.
After a median follow-up of 41.6 months, the median IRC-assessed PFS in all treated patients was not reached in the ublituximab plus ibrutinib group after 15 PFS events but was 35.9 months in the ibrutinib group after 25 PFS events (hazard ratio, 0.46; 95% confidence interval, 0.24-0.87; P = .016).
Undetectable minimal residual disease was also seen in 42% of the combination arm, compared with 6% of the ibrutinib arm.
What types of adverse events were found in the trial?
The researchers found mostly mild and known side effects of ibrutinib. More atrial fibrillation and neutropenia were seen in the antibody group, but this was not marked.
Most adverse events were of grade 1 or 2. The most common grade 3 and 4 adverse events were neutropenia (11 [19%] patients in the ublituximab plus ibrutinib group and 7 [12%] in the ibrutinib group), anemia (5 [8%] and 5 [9%], respectively), and diarrhea (6 [10%] and 3 [5%], respectively).
What about serious adverse events?
Hospitalization from infection was seen, as expected. There were two cardiac arrests and an unexplained death, across both arms, which was concerning, given the known association of ibrutinib with ventricular arrhythmia and sudden death. There were also several hemorrhages, including one fatal one, which was again consistent with the known side effects of ibrutinib.
Are there treatments comparable with ublituximab plus ibrutinib that clinicians should perhaps first consider using?
In terms of other anti-CD20 antibodies, we have two randomized trials that have failed to show a benefit from adding rituximab to ibrutinib.
Obinutuzumab, like ublituximab, is also a next-generation glycoengineered antibody, and it is reasonably likely that it might lead to similar results. However, the only data we have on ibrutinib with obinutuzumab are from a single arm in a more heterogeneous, lower-risk patient population, and it is unlikely that a randomized comparison will ever be done.
On the basis of these trial results, how would you use the combination of ublituximab and ibrutinib for your patients?
I would consider the addition of ublituximab to a BTK inhibitor in high-risk patients (once ublituximab is approved). I already usually use a next-generation BTK inhibitor rather than ibrutinib.
Are there any other implications of the GENUINE trial?
I think this trial underscores the importance of studying genetic subgroups of patients separately. In this case, that was done in high-risk patients, but this observation likely also applies to low-risk patients.
Most trials to date have enrolled unselected patient populations, often without stratification, and their results therefore tend to obscure the outcomes in both the very high risk (as studied here) and in the low risk (patients with immunoglobulin heavy chain variable region gene mutations).
Dr. Brown has served as a consultant for AbbVie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys, and Novartis, and has received research funding from Gilead, Loxo/Lilly, TG Therapeutics, Verastem/SecuraBio.
A version of this article first appeared on Medscape.com.
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease associated with several known genetic abnormalities, including 17p deletion (del[17p]), 11q deletion (del[11q]), and TP53 gene mutations, which are adverse prognostic markers among patients treated with chemoimmunotherapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is approved for patients with untreated, relapsed, or refractory disease, including those with del(17p). Clinicians will soon have the chance to pair it with ublituximab, a next-generation, glycoengineered, type I, anti-CD20 monoclonal antibody that binds to a unique epitope on CD20, differentiating it from rituximab, ofatumumab, and obinutuzumab. Results from the phase 3 GENUINE trial, which were recently published in The Lancet Haematology, showed that ublituximab plus ibrutinib was superior to ibrutinib alone for patients with relapsed or refractory high-risk CLL.
This news organization spoke with Jennifer R. Brown, MD, PhD, director of the CLL Center and institute physician at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston, about the GENUINE trial and its potential impact on treatment choices going forward.
What type of patients were treated in the GENUINE trial?
Dr. Brown: This is a trial among relapsed/refractory CLL patients with 17p or 11q deletion or TP53 mutation. Patients aged 18 years or older with CLL who warranted treatment, as defined by International Workshop on CLL criteria, were eligible if they had previously received at least two cycles of at least one standard treatment regimen, had an Eastern Cooperative Oncology Group performance status of 2 or lower, and had high-risk cytogenetics, defined as the presence of at least one of del(17p), del(11q), or TP53 mutation confirmed by a central laboratory with fluorescence in situ hybridization and/or next-generation sequencing.
What were the main outcomes of the trial?
Originally, the GENUINE trial had coprimary endpoints of progression-free survival (PFS) and overall response rate. Because of slow accrual, it was amended to have one primary endpoint of independent review committee (IRC)–assessed ORR.
IRC-assessed ORR was improved from 65% to 83% with the addition of ublituximab. PFS also improved significantly in the ublituximab group, with an even greater improvement when the analysis was limited to those with del(17p) or TP53 aberrancy, but this outcome was limited by the reduced sample size of the study as well as the relatively short PFS of the ibrutinib arm.
After a median follow-up of 41.6 months, the median IRC-assessed PFS in all treated patients was not reached in the ublituximab plus ibrutinib group after 15 PFS events but was 35.9 months in the ibrutinib group after 25 PFS events (hazard ratio, 0.46; 95% confidence interval, 0.24-0.87; P = .016).
Undetectable minimal residual disease was also seen in 42% of the combination arm, compared with 6% of the ibrutinib arm.
What types of adverse events were found in the trial?
The researchers found mostly mild and known side effects of ibrutinib. More atrial fibrillation and neutropenia were seen in the antibody group, but this was not marked.
Most adverse events were of grade 1 or 2. The most common grade 3 and 4 adverse events were neutropenia (11 [19%] patients in the ublituximab plus ibrutinib group and 7 [12%] in the ibrutinib group), anemia (5 [8%] and 5 [9%], respectively), and diarrhea (6 [10%] and 3 [5%], respectively).
What about serious adverse events?
Hospitalization from infection was seen, as expected. There were two cardiac arrests and an unexplained death, across both arms, which was concerning, given the known association of ibrutinib with ventricular arrhythmia and sudden death. There were also several hemorrhages, including one fatal one, which was again consistent with the known side effects of ibrutinib.
Are there treatments comparable with ublituximab plus ibrutinib that clinicians should perhaps first consider using?
In terms of other anti-CD20 antibodies, we have two randomized trials that have failed to show a benefit from adding rituximab to ibrutinib.
Obinutuzumab, like ublituximab, is also a next-generation glycoengineered antibody, and it is reasonably likely that it might lead to similar results. However, the only data we have on ibrutinib with obinutuzumab are from a single arm in a more heterogeneous, lower-risk patient population, and it is unlikely that a randomized comparison will ever be done.
On the basis of these trial results, how would you use the combination of ublituximab and ibrutinib for your patients?
I would consider the addition of ublituximab to a BTK inhibitor in high-risk patients (once ublituximab is approved). I already usually use a next-generation BTK inhibitor rather than ibrutinib.
Are there any other implications of the GENUINE trial?
I think this trial underscores the importance of studying genetic subgroups of patients separately. In this case, that was done in high-risk patients, but this observation likely also applies to low-risk patients.
Most trials to date have enrolled unselected patient populations, often without stratification, and their results therefore tend to obscure the outcomes in both the very high risk (as studied here) and in the low risk (patients with immunoglobulin heavy chain variable region gene mutations).
Dr. Brown has served as a consultant for AbbVie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys, and Novartis, and has received research funding from Gilead, Loxo/Lilly, TG Therapeutics, Verastem/SecuraBio.
A version of this article first appeared on Medscape.com.
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease associated with several known genetic abnormalities, including 17p deletion (del[17p]), 11q deletion (del[11q]), and TP53 gene mutations, which are adverse prognostic markers among patients treated with chemoimmunotherapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is approved for patients with untreated, relapsed, or refractory disease, including those with del(17p). Clinicians will soon have the chance to pair it with ublituximab, a next-generation, glycoengineered, type I, anti-CD20 monoclonal antibody that binds to a unique epitope on CD20, differentiating it from rituximab, ofatumumab, and obinutuzumab. Results from the phase 3 GENUINE trial, which were recently published in The Lancet Haematology, showed that ublituximab plus ibrutinib was superior to ibrutinib alone for patients with relapsed or refractory high-risk CLL.
This news organization spoke with Jennifer R. Brown, MD, PhD, director of the CLL Center and institute physician at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston, about the GENUINE trial and its potential impact on treatment choices going forward.
What type of patients were treated in the GENUINE trial?
Dr. Brown: This is a trial among relapsed/refractory CLL patients with 17p or 11q deletion or TP53 mutation. Patients aged 18 years or older with CLL who warranted treatment, as defined by International Workshop on CLL criteria, were eligible if they had previously received at least two cycles of at least one standard treatment regimen, had an Eastern Cooperative Oncology Group performance status of 2 or lower, and had high-risk cytogenetics, defined as the presence of at least one of del(17p), del(11q), or TP53 mutation confirmed by a central laboratory with fluorescence in situ hybridization and/or next-generation sequencing.
What were the main outcomes of the trial?
Originally, the GENUINE trial had coprimary endpoints of progression-free survival (PFS) and overall response rate. Because of slow accrual, it was amended to have one primary endpoint of independent review committee (IRC)–assessed ORR.
IRC-assessed ORR was improved from 65% to 83% with the addition of ublituximab. PFS also improved significantly in the ublituximab group, with an even greater improvement when the analysis was limited to those with del(17p) or TP53 aberrancy, but this outcome was limited by the reduced sample size of the study as well as the relatively short PFS of the ibrutinib arm.
After a median follow-up of 41.6 months, the median IRC-assessed PFS in all treated patients was not reached in the ublituximab plus ibrutinib group after 15 PFS events but was 35.9 months in the ibrutinib group after 25 PFS events (hazard ratio, 0.46; 95% confidence interval, 0.24-0.87; P = .016).
Undetectable minimal residual disease was also seen in 42% of the combination arm, compared with 6% of the ibrutinib arm.
What types of adverse events were found in the trial?
The researchers found mostly mild and known side effects of ibrutinib. More atrial fibrillation and neutropenia were seen in the antibody group, but this was not marked.
Most adverse events were of grade 1 or 2. The most common grade 3 and 4 adverse events were neutropenia (11 [19%] patients in the ublituximab plus ibrutinib group and 7 [12%] in the ibrutinib group), anemia (5 [8%] and 5 [9%], respectively), and diarrhea (6 [10%] and 3 [5%], respectively).
What about serious adverse events?
Hospitalization from infection was seen, as expected. There were two cardiac arrests and an unexplained death, across both arms, which was concerning, given the known association of ibrutinib with ventricular arrhythmia and sudden death. There were also several hemorrhages, including one fatal one, which was again consistent with the known side effects of ibrutinib.
Are there treatments comparable with ublituximab plus ibrutinib that clinicians should perhaps first consider using?
In terms of other anti-CD20 antibodies, we have two randomized trials that have failed to show a benefit from adding rituximab to ibrutinib.
Obinutuzumab, like ublituximab, is also a next-generation glycoengineered antibody, and it is reasonably likely that it might lead to similar results. However, the only data we have on ibrutinib with obinutuzumab are from a single arm in a more heterogeneous, lower-risk patient population, and it is unlikely that a randomized comparison will ever be done.
On the basis of these trial results, how would you use the combination of ublituximab and ibrutinib for your patients?
I would consider the addition of ublituximab to a BTK inhibitor in high-risk patients (once ublituximab is approved). I already usually use a next-generation BTK inhibitor rather than ibrutinib.
Are there any other implications of the GENUINE trial?
I think this trial underscores the importance of studying genetic subgroups of patients separately. In this case, that was done in high-risk patients, but this observation likely also applies to low-risk patients.
Most trials to date have enrolled unselected patient populations, often without stratification, and their results therefore tend to obscure the outcomes in both the very high risk (as studied here) and in the low risk (patients with immunoglobulin heavy chain variable region gene mutations).
Dr. Brown has served as a consultant for AbbVie, Acerta/AstraZeneca, Beigene, Bristol-Myers Squibb/Juno/Celgene, Catapult, Genentech/Roche, Janssen, MEI Pharma, Morphosys, and Novartis, and has received research funding from Gilead, Loxo/Lilly, TG Therapeutics, Verastem/SecuraBio.
A version of this article first appeared on Medscape.com.
Ten reasons airborne transmission of SARS-CoV-2 appears airtight
The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.
Not that it’s without controversy.
The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.
“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).
“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.
“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.
“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.
Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
Top 10 reasons
They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:
- The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
- Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
- Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
- Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
- Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
- Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
- Investigators found SARS-CoV-2 in hospital air filters and building ducts.
- It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
- No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
- Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.
“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.
“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.
The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
Response to a review
The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”
However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”
The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”
Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.
“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”
As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”
The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.
A version of this article first appeared on Medscape.com.
The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.
Not that it’s without controversy.
The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.
“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).
“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.
“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.
“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.
Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
Top 10 reasons
They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:
- The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
- Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
- Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
- Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
- Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
- Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
- Investigators found SARS-CoV-2 in hospital air filters and building ducts.
- It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
- No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
- Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.
“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.
“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.
The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
Response to a review
The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”
However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”
The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”
Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.
“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”
As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”
The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.
A version of this article first appeared on Medscape.com.
The scientific evidence for airborne transmission of the SARS-CoV-2 virus from different researchers all point in the same direction – that infectious aerosols are the principal means of person-to-person transmission, according to experts.
Not that it’s without controversy.
The science backing aerosol transmission “is clear-cut, but it is not accepted in many circles,” Trisha Greenhalgh, PhD, said in an interview.
“In particular, some in the evidence-based medicine movement and some infectious diseases clinicians are remarkably resistant to the evidence,” added Dr. Greenhalgh, professor of primary care health sciences at the University of Oxford (England).
“It’s very hard to see why, since the evidence all stacks up,” Dr. Greenhalgh said.
“The scientific evidence on spread from both near-field and far-field aerosols has been clear since early on in the pandemic, but there was resistance to acknowledging this in some circles, including the medical journals,” Joseph G. Allen, DSc, MPH, told this news organization when asked to comment.
“This is the week the dam broke. Three new commentaries came out … in top medical journals – BMJ, The Lancet, JAMA – all making the same point that aerosols are the dominant mode of transmission,” added Dr. Allen, associate professor of exposure assessment science at the Harvard T.H. Chan School of Public Health in Boston.
Dr. Greenhalgh and colleagues point to an increase in COVID-19 cases in the aftermath of so-called “super-spreader” events, spread of SARS-CoV-2 to people across different hotel rooms, and the relatively lower transmission detected after outdoor events.
Top 10 reasons
They outlined 10 scientific reasons backing airborne transmission in a commentary published online April 15 in The Lancet:
- The dominance of airborne transmission is supported by long-range transmission observed at super-spreader events.
- Long-range transmission has been reported among rooms at COVID-19 quarantine hotels, settings where infected people never spent time in the same room.
- Asymptomatic individuals account for an estimated 33%-59% of SARS-CoV-2 transmission, and could be spreading the virus through speaking, which produces thousands of aerosol particles and few large droplets.
- Transmission outdoors and in well-ventilated indoor spaces is lower than in enclosed spaces.
- Nosocomial infections are reported in health care settings where protective measures address large droplets but not aerosols.
- Viable SARS-CoV-2 has been detected in the air of hospital rooms and in the car of an infected person.
- Investigators found SARS-CoV-2 in hospital air filters and building ducts.
- It’s not just humans – infected animals can infect animals in other cages connected only through an air duct.
- No strong evidence refutes airborne transmission, and contact tracing supports secondary transmission in crowded, poorly ventilated indoor spaces.
- Only limited evidence supports other means of SARS-CoV-2 transmission, including through fomites or large droplets.
“We thought we’d summarize [the evidence] to clarify the arguments for and against. We looked hard for evidence against but found none,” Dr. Greenhalgh said.
“Although other routes can contribute, we believe that the airborne route is likely to be dominant,” the authors note.
The evidence on airborne transmission was there very early on but the Centers for Disease Control and Prevention, World Health Organization, and others repeated the message that the primary concern was droplets and fomites.
Response to a review
The top 10 list is also part rebuttal of a systematic review funded by the WHO and published last month that points to inconclusive evidence for airborne transmission. The researchers involved with that review state that “the lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions to be drawn about airborne transmission.”
However, Dr. Greenhalgh and colleagues note that “this conclusion, and the wide circulation of the review’s findings, is concerning because of the public health implications.”
The current authors also argue that enough evidence already exists on airborne transmission. “Policy should change. We don’t need more research on this topic; we need different policy,” Dr. Greenhalgh said. “We need ventilation front and center, air filtration when necessary, and better-fitting masks worn whenever indoors.”
Dr. Allen agreed that guidance hasn’t always kept pace with the science. “With all of the new evidence accumulated on airborne transmission since last winter, there is still widespread confusion in the public about modes of transmission,” he said. Dr. Allen also serves as commissioner of The Lancet COVID-19 Commission and is chair of the commission’s Task Force on Safe Work, Safe Schools, and Safe Travel.
“It was only just last week that CDC pulled back on guidance on ‘deep cleaning’ and in its place correctly said that the risk from touching surfaces is low,” he added. “The science has been clear on this for over a year, but official guidance was only recently updated.”
As a result, many companies and organizations continued to focus on “hygiene theatre,” Dr. Allen said, “wasting resources on overcleaning surfaces. Unbelievably, many schools still close for an entire day each week for deep cleaning and some still quarantine library books. The message that shared air is the problem, not shared surfaces, is a message that still needs to be reinforced.”
The National Institute for Health Research, Economic and Social Research Council, and Wellcome support Dr. Greenhalgh’s research. Dr. Greenhalgh and Dr. Allen had no relevant financial relationships to disclose.
A version of this article first appeared on Medscape.com.
What COVID did to MD income in 2020
, according to the Medscape Physician Compensation Report 2021: The Recovery Begins.
Almost 18,000 physicians in more than 29 specialties told Medscape about their income, hours worked, greatest challenges, and the unexpected impact of COVID-19 on their compensation.
How many physicians avoided massive losses
When the pandemic started around March 2020, “a great many physicians saw reductions in volume at first,” says Robert Pearl, MD, former CEO of the Permanente Medical Group and a professor at Stanford (Calif.) University.
Medscape’s survey report shows that a staggering 44% saw a 1%-25% reduction in patient volume, and 9% saw a 26%-50% decline. “That is indeed breathtaking,” Dr. Pearl says.
Several key factors saved many practices from hemorrhaging money, says Michael Belkin, JD, divisional vice president at Merritt Hawkins and Associates in Dallas. “Many physicians used the federal Paycheck Protection Program [PPP] to help keep themselves afloat,” he says. “A large percentage reduced their staff, which reduced their expenses, and many got some of their volume back by transitioning to telemedicine.”
In a 2020 survey for the Physicians Foundation, conducted by Merritt Hawkins, 48% of physicians said their practice had received PPP support, and most of those said the support was enough to allow them to stay open without reducing staff. Only 6% of practices that received PPP support did not stay open.
Telemedicine helped many practices
Early in the pandemic, Medicare reimbursements for telemedicine were equal with those for face-to-face visits. “Since telemedicine takes a third less time than an inpatient visit, doctors could see more patients,” Dr. Pearl says.
The switch was almost instantaneous in some practices. Within 3 days, a 200-provider multispecialty practice in Wilmington, N.C., went from not using telehealth to its being used by all physicians, the Medical Group Management Association reported. By late April, the practice was already back up to about 70% of normal overall production.
However, telemedicine could not help every specialty equally. “Generally, allergists can’t do their allergy testing virtually, and patients with mild problems probably put off visits,” Dr. Pearl says. Allergists experienced a large percentage decline in compensation, according to Medscape’s survey. For some, income fell from $301,000 the prior year to $274,000 this year.
Primary care struggled
Primary care physicians posted lower compensation than they did the prior year, but most rebounded to some degree. A study released in June 2020 projected that, even with telemedicine, primary care physicians would lose an average of $67,774 for the year.
However, Medscape’s survey found that internists’ average compensation declined from $251,000 in the prior year to $248,000, and average family physicians’ compensation actually rose from $234,000.
Pediatricians had a harder slog. Their average compensation sank from $232,000 to $221,000, according to the report. Even with telemedicine, parents of young children were not contacting the doctor. In May 2020, visits by children aged 3-5 years were down by 56%.
Many proceduralists recovered
Procedure-oriented specialties were particularly hard-hit at first, because many hospitals and some states banned all elective surgeries at the beginning of the pandemic.
“In March and April, ophthalmology practices were virtually at a standstill,” says John B. Pinto, an ophthalmology practice management consultant in San Diego. “But by the fourth quarter, operations were back to normal. Practices were fully open, and patients were coming back in.”
Medscape’s survey shows that, by year’s end, compensation was about the same as the year before for orthopedic surgeons ($511,000 in both the 2020 and 2021 reports); cardiologists actually did better ($438,000 in our 2020 report and $459,000 in 2021); and ophthalmologists’ compensation was about the same ($378,000 in our prior report and $379,000 in 2021).
Some other proceduralists, however, did not do as well. Otolaryngologists’ compensation fell to $417,000, the second-biggest percentage drop. “This may be because otolaryngologists’ chief procedures are tonsillectomies, sinus surgery, and nasal surgery, which can be put off,” Dr. Pearl says.
Anesthesiologists, who depend on surgical volume, also did not earn as much in 2020. Their compensation declined from $398,000 in our 2020 report to $378,000 in Medscape’s 2021 report.
“Not only has 70% of our revenue disappeared, but our physicians are still working every day,” an independent anesthesiology practice in Alabama told the MGMA early in the pandemic.
Plastic surgeons now the top earners
The biggest increase in compensation by far was made by plastic surgeons, whose income rose 9.8% over the year before, to $526,000. This put them at the top of the list
Dr. Pearl adds that plastic surgeons can perform their procedures in their offices, rather than in a hospital, where elective surgeries were often canceled.
Mr. Belkin says specialties other than plastic surgery had been offering more boutique cosmetic care even before the pandemic. In 2020, nonsurgical cosmetic procedures such as neurotoxin therapy, dermal filler procedures, chemical peels, and hair removal earned $3.1 billion in revenue, according to a survey by the Aesthetic Society.
Other specialties that earned more even during COVID
In Medscape’s survey, several specialties actually earned more during the pandemic than in 2019. Some specialties, such as critical care and public health, were integral in managing COVID patients and the pandemic.
However, some specialties involved in COVID care did not see an increase. Compensation for infectious disease specialists (at $245,000) and emergency medicine specialists (at $354,000) remained basically unchanged from the prior year, and for pulmonologists, it was slightly down.
Emergency departments reported decreases in volume of 40% or more early in the pandemic, according to the American College of Emergency Physicians. It was reported that patients were avoiding EDs for fear of contracting COVID, and car accidents were down because people ventured out less.
In this year’s report, psychiatrists saw a modest rise in compensation, to $275,000. “There has been an increase in mental health visits in the pandemic,” Dr. Pearl says. In 2020, about 4 in 10 adults in the United States reported symptoms of anxiety or depressive disorder, up from 1 in 10 adults the prior year. In addition, psychiatrists were third on the list of Merritt Hawkins’ most requested recruiting engagements.
Oncologists saw a rise in compensation, from $377,000 to $403,000. “Volume likely did not fall because cancer patients would go through with their chemotherapy in spite of the pandemic,” Dr. Pearl says. “The increase in income might have to do with the usual inflation in the cost of chemotherapy drugs.” Dr. Pinto saw the same trend for retinal surgeons, whose care also cannot be delayed.
Medscape’s survey also reports increases in compensation for rheumatologists, endocrinologists, and neurologists, but it reports small declines among dermatologists, radiologists, and gastroenterologists.
Gender-based pay gap remains in place
The gender-based pay gap in this year’s report is similar to that seen in Medscape’s report for the prior year. Men earned 27% more than women in 2021, compared with 25% more the year before. Some physicians commented that more women physicians maintained flexible or shorter work schedules to help with children who could not go into school.
“Having to be a full-time physician, full-time mom, and full-time teacher during our surge was unbelievable,” a primary care pediatrician in group practice and mother of two reported in November. “I felt pulled in all directions and didn’t do anything well.”
In addition, “men dominate some specialties that seem to have seen a smaller drop in volume in the pandemic, such as emergency medicine, infectious disease, pulmonology, and oncology,” says Halee Fischer-Wright, MD, CEO of MGMA.
Employed physicians shared their employers’ pain
Employed physicians, who typically work at hospitals, shared the financial pains of their institutions, particularly in the early stages of the pandemic. In April, hospital admissions were 34.1% below prepandemic levels, according to a study published in Health Affairs. That figure had risen by June, but it was still 8.3% below prepandemic volume.
By the end of the year, many hospitals and hospital systems were in the black, thanks in large part to generous federal subsidies, but actual operations still lost money for the year. Altogether, 42% of them posted an operational loss in 2020, up from the 23% in 2019, according to a survey by Moody’s Investors Service.
Medscape’s report shows that many employed physicians lost pay in 2020, and for many, pay had not returned to pre-COVID levels. Only 28% of primary care physicians and 32% of specialists who lost pay have seen it restored, according to the report. In addition, 15% of surveyed physicians did not receive an annual raise.
Many employed doctors are paid on the basis of relative value units (RVUs), which is a measure of the value of their work. In many cases, there was not enough work to reach RVU thresholds. Would hospitals and other employers lower RVU targets to meet the problem? “I haven’t seen our clients make concessions to providers along those lines,” Mr. Belkin says.
Physicians had to work longer hours
The Medscape report also found that in 2020, physicians saw fewer patients because each visit took longer.
“With the threat of COVID, in-person visits take more time than before,” Mr. Belkin says. “Physicians and staff have to prepare the exam room after each visit, and doctors must spend more time answering patients’ questions about COVID.”
“The new protocols to keep everyone safe add time between patients, and physicians have to answer patients’ questions about the pandemic and vaccines,” Dr. Fischer-Wright says. “You might see a 20% increase in time spent just on these non–revenue-generating COVID activities.”
Physicians still like their specialty
Although 2020 was a challenging year for physicians, the percentage of those who were satisfied with their specialty choice generally did not slip from the year before. It actually rose for several specialties – most notably, rheumatology, pulmonology, physical medicine and rehabilitation, and nephrology.
One specialty saw a decline in satisfaction with their specialty choice, and that was public health and preventive medicine, which plummeted 16 percentage points to 67% – putting it at the bottom of the list.
Even before the pandemic, many public health departments were chronically underfunded. This problem was possibly exacerbated by the pressures to keep up with COVID reporting and testing responsibilities.
Conclusion
Although 2020 was a wild ride for many physicians, many came out of it with only minor reductions in overall compensation, and some saw increases. Still, some specialties and many individuals experienced terrible financial stress and had to make changes in their lives and their spending in order to stay afloat.
“The biggest inhibitor to getting back to normal had to do with doctors who did not want to return because they did not want to risk getting COVID,” Dr. Pinto reports. But he notes that by February 2021 most doctors were completely vaccinated and could feel safe again.
A version of this article first appeared on Medscape.com.
, according to the Medscape Physician Compensation Report 2021: The Recovery Begins.
Almost 18,000 physicians in more than 29 specialties told Medscape about their income, hours worked, greatest challenges, and the unexpected impact of COVID-19 on their compensation.
How many physicians avoided massive losses
When the pandemic started around March 2020, “a great many physicians saw reductions in volume at first,” says Robert Pearl, MD, former CEO of the Permanente Medical Group and a professor at Stanford (Calif.) University.
Medscape’s survey report shows that a staggering 44% saw a 1%-25% reduction in patient volume, and 9% saw a 26%-50% decline. “That is indeed breathtaking,” Dr. Pearl says.
Several key factors saved many practices from hemorrhaging money, says Michael Belkin, JD, divisional vice president at Merritt Hawkins and Associates in Dallas. “Many physicians used the federal Paycheck Protection Program [PPP] to help keep themselves afloat,” he says. “A large percentage reduced their staff, which reduced their expenses, and many got some of their volume back by transitioning to telemedicine.”
In a 2020 survey for the Physicians Foundation, conducted by Merritt Hawkins, 48% of physicians said their practice had received PPP support, and most of those said the support was enough to allow them to stay open without reducing staff. Only 6% of practices that received PPP support did not stay open.
Telemedicine helped many practices
Early in the pandemic, Medicare reimbursements for telemedicine were equal with those for face-to-face visits. “Since telemedicine takes a third less time than an inpatient visit, doctors could see more patients,” Dr. Pearl says.
The switch was almost instantaneous in some practices. Within 3 days, a 200-provider multispecialty practice in Wilmington, N.C., went from not using telehealth to its being used by all physicians, the Medical Group Management Association reported. By late April, the practice was already back up to about 70% of normal overall production.
However, telemedicine could not help every specialty equally. “Generally, allergists can’t do their allergy testing virtually, and patients with mild problems probably put off visits,” Dr. Pearl says. Allergists experienced a large percentage decline in compensation, according to Medscape’s survey. For some, income fell from $301,000 the prior year to $274,000 this year.
Primary care struggled
Primary care physicians posted lower compensation than they did the prior year, but most rebounded to some degree. A study released in June 2020 projected that, even with telemedicine, primary care physicians would lose an average of $67,774 for the year.
However, Medscape’s survey found that internists’ average compensation declined from $251,000 in the prior year to $248,000, and average family physicians’ compensation actually rose from $234,000.
Pediatricians had a harder slog. Their average compensation sank from $232,000 to $221,000, according to the report. Even with telemedicine, parents of young children were not contacting the doctor. In May 2020, visits by children aged 3-5 years were down by 56%.
Many proceduralists recovered
Procedure-oriented specialties were particularly hard-hit at first, because many hospitals and some states banned all elective surgeries at the beginning of the pandemic.
“In March and April, ophthalmology practices were virtually at a standstill,” says John B. Pinto, an ophthalmology practice management consultant in San Diego. “But by the fourth quarter, operations were back to normal. Practices were fully open, and patients were coming back in.”
Medscape’s survey shows that, by year’s end, compensation was about the same as the year before for orthopedic surgeons ($511,000 in both the 2020 and 2021 reports); cardiologists actually did better ($438,000 in our 2020 report and $459,000 in 2021); and ophthalmologists’ compensation was about the same ($378,000 in our prior report and $379,000 in 2021).
Some other proceduralists, however, did not do as well. Otolaryngologists’ compensation fell to $417,000, the second-biggest percentage drop. “This may be because otolaryngologists’ chief procedures are tonsillectomies, sinus surgery, and nasal surgery, which can be put off,” Dr. Pearl says.
Anesthesiologists, who depend on surgical volume, also did not earn as much in 2020. Their compensation declined from $398,000 in our 2020 report to $378,000 in Medscape’s 2021 report.
“Not only has 70% of our revenue disappeared, but our physicians are still working every day,” an independent anesthesiology practice in Alabama told the MGMA early in the pandemic.
Plastic surgeons now the top earners
The biggest increase in compensation by far was made by plastic surgeons, whose income rose 9.8% over the year before, to $526,000. This put them at the top of the list
Dr. Pearl adds that plastic surgeons can perform their procedures in their offices, rather than in a hospital, where elective surgeries were often canceled.
Mr. Belkin says specialties other than plastic surgery had been offering more boutique cosmetic care even before the pandemic. In 2020, nonsurgical cosmetic procedures such as neurotoxin therapy, dermal filler procedures, chemical peels, and hair removal earned $3.1 billion in revenue, according to a survey by the Aesthetic Society.
Other specialties that earned more even during COVID
In Medscape’s survey, several specialties actually earned more during the pandemic than in 2019. Some specialties, such as critical care and public health, were integral in managing COVID patients and the pandemic.
However, some specialties involved in COVID care did not see an increase. Compensation for infectious disease specialists (at $245,000) and emergency medicine specialists (at $354,000) remained basically unchanged from the prior year, and for pulmonologists, it was slightly down.
Emergency departments reported decreases in volume of 40% or more early in the pandemic, according to the American College of Emergency Physicians. It was reported that patients were avoiding EDs for fear of contracting COVID, and car accidents were down because people ventured out less.
In this year’s report, psychiatrists saw a modest rise in compensation, to $275,000. “There has been an increase in mental health visits in the pandemic,” Dr. Pearl says. In 2020, about 4 in 10 adults in the United States reported symptoms of anxiety or depressive disorder, up from 1 in 10 adults the prior year. In addition, psychiatrists were third on the list of Merritt Hawkins’ most requested recruiting engagements.
Oncologists saw a rise in compensation, from $377,000 to $403,000. “Volume likely did not fall because cancer patients would go through with their chemotherapy in spite of the pandemic,” Dr. Pearl says. “The increase in income might have to do with the usual inflation in the cost of chemotherapy drugs.” Dr. Pinto saw the same trend for retinal surgeons, whose care also cannot be delayed.
Medscape’s survey also reports increases in compensation for rheumatologists, endocrinologists, and neurologists, but it reports small declines among dermatologists, radiologists, and gastroenterologists.
Gender-based pay gap remains in place
The gender-based pay gap in this year’s report is similar to that seen in Medscape’s report for the prior year. Men earned 27% more than women in 2021, compared with 25% more the year before. Some physicians commented that more women physicians maintained flexible or shorter work schedules to help with children who could not go into school.
“Having to be a full-time physician, full-time mom, and full-time teacher during our surge was unbelievable,” a primary care pediatrician in group practice and mother of two reported in November. “I felt pulled in all directions and didn’t do anything well.”
In addition, “men dominate some specialties that seem to have seen a smaller drop in volume in the pandemic, such as emergency medicine, infectious disease, pulmonology, and oncology,” says Halee Fischer-Wright, MD, CEO of MGMA.
Employed physicians shared their employers’ pain
Employed physicians, who typically work at hospitals, shared the financial pains of their institutions, particularly in the early stages of the pandemic. In April, hospital admissions were 34.1% below prepandemic levels, according to a study published in Health Affairs. That figure had risen by June, but it was still 8.3% below prepandemic volume.
By the end of the year, many hospitals and hospital systems were in the black, thanks in large part to generous federal subsidies, but actual operations still lost money for the year. Altogether, 42% of them posted an operational loss in 2020, up from the 23% in 2019, according to a survey by Moody’s Investors Service.
Medscape’s report shows that many employed physicians lost pay in 2020, and for many, pay had not returned to pre-COVID levels. Only 28% of primary care physicians and 32% of specialists who lost pay have seen it restored, according to the report. In addition, 15% of surveyed physicians did not receive an annual raise.
Many employed doctors are paid on the basis of relative value units (RVUs), which is a measure of the value of their work. In many cases, there was not enough work to reach RVU thresholds. Would hospitals and other employers lower RVU targets to meet the problem? “I haven’t seen our clients make concessions to providers along those lines,” Mr. Belkin says.
Physicians had to work longer hours
The Medscape report also found that in 2020, physicians saw fewer patients because each visit took longer.
“With the threat of COVID, in-person visits take more time than before,” Mr. Belkin says. “Physicians and staff have to prepare the exam room after each visit, and doctors must spend more time answering patients’ questions about COVID.”
“The new protocols to keep everyone safe add time between patients, and physicians have to answer patients’ questions about the pandemic and vaccines,” Dr. Fischer-Wright says. “You might see a 20% increase in time spent just on these non–revenue-generating COVID activities.”
Physicians still like their specialty
Although 2020 was a challenging year for physicians, the percentage of those who were satisfied with their specialty choice generally did not slip from the year before. It actually rose for several specialties – most notably, rheumatology, pulmonology, physical medicine and rehabilitation, and nephrology.
One specialty saw a decline in satisfaction with their specialty choice, and that was public health and preventive medicine, which plummeted 16 percentage points to 67% – putting it at the bottom of the list.
Even before the pandemic, many public health departments were chronically underfunded. This problem was possibly exacerbated by the pressures to keep up with COVID reporting and testing responsibilities.
Conclusion
Although 2020 was a wild ride for many physicians, many came out of it with only minor reductions in overall compensation, and some saw increases. Still, some specialties and many individuals experienced terrible financial stress and had to make changes in their lives and their spending in order to stay afloat.
“The biggest inhibitor to getting back to normal had to do with doctors who did not want to return because they did not want to risk getting COVID,” Dr. Pinto reports. But he notes that by February 2021 most doctors were completely vaccinated and could feel safe again.
A version of this article first appeared on Medscape.com.
, according to the Medscape Physician Compensation Report 2021: The Recovery Begins.
Almost 18,000 physicians in more than 29 specialties told Medscape about their income, hours worked, greatest challenges, and the unexpected impact of COVID-19 on their compensation.
How many physicians avoided massive losses
When the pandemic started around March 2020, “a great many physicians saw reductions in volume at first,” says Robert Pearl, MD, former CEO of the Permanente Medical Group and a professor at Stanford (Calif.) University.
Medscape’s survey report shows that a staggering 44% saw a 1%-25% reduction in patient volume, and 9% saw a 26%-50% decline. “That is indeed breathtaking,” Dr. Pearl says.
Several key factors saved many practices from hemorrhaging money, says Michael Belkin, JD, divisional vice president at Merritt Hawkins and Associates in Dallas. “Many physicians used the federal Paycheck Protection Program [PPP] to help keep themselves afloat,” he says. “A large percentage reduced their staff, which reduced their expenses, and many got some of their volume back by transitioning to telemedicine.”
In a 2020 survey for the Physicians Foundation, conducted by Merritt Hawkins, 48% of physicians said their practice had received PPP support, and most of those said the support was enough to allow them to stay open without reducing staff. Only 6% of practices that received PPP support did not stay open.
Telemedicine helped many practices
Early in the pandemic, Medicare reimbursements for telemedicine were equal with those for face-to-face visits. “Since telemedicine takes a third less time than an inpatient visit, doctors could see more patients,” Dr. Pearl says.
The switch was almost instantaneous in some practices. Within 3 days, a 200-provider multispecialty practice in Wilmington, N.C., went from not using telehealth to its being used by all physicians, the Medical Group Management Association reported. By late April, the practice was already back up to about 70% of normal overall production.
However, telemedicine could not help every specialty equally. “Generally, allergists can’t do their allergy testing virtually, and patients with mild problems probably put off visits,” Dr. Pearl says. Allergists experienced a large percentage decline in compensation, according to Medscape’s survey. For some, income fell from $301,000 the prior year to $274,000 this year.
Primary care struggled
Primary care physicians posted lower compensation than they did the prior year, but most rebounded to some degree. A study released in June 2020 projected that, even with telemedicine, primary care physicians would lose an average of $67,774 for the year.
However, Medscape’s survey found that internists’ average compensation declined from $251,000 in the prior year to $248,000, and average family physicians’ compensation actually rose from $234,000.
Pediatricians had a harder slog. Their average compensation sank from $232,000 to $221,000, according to the report. Even with telemedicine, parents of young children were not contacting the doctor. In May 2020, visits by children aged 3-5 years were down by 56%.
Many proceduralists recovered
Procedure-oriented specialties were particularly hard-hit at first, because many hospitals and some states banned all elective surgeries at the beginning of the pandemic.
“In March and April, ophthalmology practices were virtually at a standstill,” says John B. Pinto, an ophthalmology practice management consultant in San Diego. “But by the fourth quarter, operations were back to normal. Practices were fully open, and patients were coming back in.”
Medscape’s survey shows that, by year’s end, compensation was about the same as the year before for orthopedic surgeons ($511,000 in both the 2020 and 2021 reports); cardiologists actually did better ($438,000 in our 2020 report and $459,000 in 2021); and ophthalmologists’ compensation was about the same ($378,000 in our prior report and $379,000 in 2021).
Some other proceduralists, however, did not do as well. Otolaryngologists’ compensation fell to $417,000, the second-biggest percentage drop. “This may be because otolaryngologists’ chief procedures are tonsillectomies, sinus surgery, and nasal surgery, which can be put off,” Dr. Pearl says.
Anesthesiologists, who depend on surgical volume, also did not earn as much in 2020. Their compensation declined from $398,000 in our 2020 report to $378,000 in Medscape’s 2021 report.
“Not only has 70% of our revenue disappeared, but our physicians are still working every day,” an independent anesthesiology practice in Alabama told the MGMA early in the pandemic.
Plastic surgeons now the top earners
The biggest increase in compensation by far was made by plastic surgeons, whose income rose 9.8% over the year before, to $526,000. This put them at the top of the list
Dr. Pearl adds that plastic surgeons can perform their procedures in their offices, rather than in a hospital, where elective surgeries were often canceled.
Mr. Belkin says specialties other than plastic surgery had been offering more boutique cosmetic care even before the pandemic. In 2020, nonsurgical cosmetic procedures such as neurotoxin therapy, dermal filler procedures, chemical peels, and hair removal earned $3.1 billion in revenue, according to a survey by the Aesthetic Society.
Other specialties that earned more even during COVID
In Medscape’s survey, several specialties actually earned more during the pandemic than in 2019. Some specialties, such as critical care and public health, were integral in managing COVID patients and the pandemic.
However, some specialties involved in COVID care did not see an increase. Compensation for infectious disease specialists (at $245,000) and emergency medicine specialists (at $354,000) remained basically unchanged from the prior year, and for pulmonologists, it was slightly down.
Emergency departments reported decreases in volume of 40% or more early in the pandemic, according to the American College of Emergency Physicians. It was reported that patients were avoiding EDs for fear of contracting COVID, and car accidents were down because people ventured out less.
In this year’s report, psychiatrists saw a modest rise in compensation, to $275,000. “There has been an increase in mental health visits in the pandemic,” Dr. Pearl says. In 2020, about 4 in 10 adults in the United States reported symptoms of anxiety or depressive disorder, up from 1 in 10 adults the prior year. In addition, psychiatrists were third on the list of Merritt Hawkins’ most requested recruiting engagements.
Oncologists saw a rise in compensation, from $377,000 to $403,000. “Volume likely did not fall because cancer patients would go through with their chemotherapy in spite of the pandemic,” Dr. Pearl says. “The increase in income might have to do with the usual inflation in the cost of chemotherapy drugs.” Dr. Pinto saw the same trend for retinal surgeons, whose care also cannot be delayed.
Medscape’s survey also reports increases in compensation for rheumatologists, endocrinologists, and neurologists, but it reports small declines among dermatologists, radiologists, and gastroenterologists.
Gender-based pay gap remains in place
The gender-based pay gap in this year’s report is similar to that seen in Medscape’s report for the prior year. Men earned 27% more than women in 2021, compared with 25% more the year before. Some physicians commented that more women physicians maintained flexible or shorter work schedules to help with children who could not go into school.
“Having to be a full-time physician, full-time mom, and full-time teacher during our surge was unbelievable,” a primary care pediatrician in group practice and mother of two reported in November. “I felt pulled in all directions and didn’t do anything well.”
In addition, “men dominate some specialties that seem to have seen a smaller drop in volume in the pandemic, such as emergency medicine, infectious disease, pulmonology, and oncology,” says Halee Fischer-Wright, MD, CEO of MGMA.
Employed physicians shared their employers’ pain
Employed physicians, who typically work at hospitals, shared the financial pains of their institutions, particularly in the early stages of the pandemic. In April, hospital admissions were 34.1% below prepandemic levels, according to a study published in Health Affairs. That figure had risen by June, but it was still 8.3% below prepandemic volume.
By the end of the year, many hospitals and hospital systems were in the black, thanks in large part to generous federal subsidies, but actual operations still lost money for the year. Altogether, 42% of them posted an operational loss in 2020, up from the 23% in 2019, according to a survey by Moody’s Investors Service.
Medscape’s report shows that many employed physicians lost pay in 2020, and for many, pay had not returned to pre-COVID levels. Only 28% of primary care physicians and 32% of specialists who lost pay have seen it restored, according to the report. In addition, 15% of surveyed physicians did not receive an annual raise.
Many employed doctors are paid on the basis of relative value units (RVUs), which is a measure of the value of their work. In many cases, there was not enough work to reach RVU thresholds. Would hospitals and other employers lower RVU targets to meet the problem? “I haven’t seen our clients make concessions to providers along those lines,” Mr. Belkin says.
Physicians had to work longer hours
The Medscape report also found that in 2020, physicians saw fewer patients because each visit took longer.
“With the threat of COVID, in-person visits take more time than before,” Mr. Belkin says. “Physicians and staff have to prepare the exam room after each visit, and doctors must spend more time answering patients’ questions about COVID.”
“The new protocols to keep everyone safe add time between patients, and physicians have to answer patients’ questions about the pandemic and vaccines,” Dr. Fischer-Wright says. “You might see a 20% increase in time spent just on these non–revenue-generating COVID activities.”
Physicians still like their specialty
Although 2020 was a challenging year for physicians, the percentage of those who were satisfied with their specialty choice generally did not slip from the year before. It actually rose for several specialties – most notably, rheumatology, pulmonology, physical medicine and rehabilitation, and nephrology.
One specialty saw a decline in satisfaction with their specialty choice, and that was public health and preventive medicine, which plummeted 16 percentage points to 67% – putting it at the bottom of the list.
Even before the pandemic, many public health departments were chronically underfunded. This problem was possibly exacerbated by the pressures to keep up with COVID reporting and testing responsibilities.
Conclusion
Although 2020 was a wild ride for many physicians, many came out of it with only minor reductions in overall compensation, and some saw increases. Still, some specialties and many individuals experienced terrible financial stress and had to make changes in their lives and their spending in order to stay afloat.
“The biggest inhibitor to getting back to normal had to do with doctors who did not want to return because they did not want to risk getting COVID,” Dr. Pinto reports. But he notes that by February 2021 most doctors were completely vaccinated and could feel safe again.
A version of this article first appeared on Medscape.com.
Open Notes
. While some clinicians consider it an unwelcome intrusion, advocates say it will improve communication and compliance.
Patient access to notes is not new. In many states, patients already have the ability to request copies of their charts, or to access truncated information via clinic websites. The difference is that most patients will now be able to click on a patient portal – such as MyChart, or other similar apps – and gain instantaneous, unfettered access to everything in their records.
Clinicians have traditionally thought of medical notes as private journal entries; but in the last few decades they have become an important component of the documentation necessary for billing, as well as evidence in the event of litigation. Now, with the implementation of the Cures Act, medical notes have evolved into a tool to communicate with the patient, rather than just among health care providers, lawyers, and billing departments.
Supporters contend that this change will make a big difference, because patients will be able to see exactly what their doctors have written, rather than just a list of confusing test results and diagnosis lists in “medicalese.”
OpenNotes, a think tank that has promoted the sharing of clinical notes with patients for years, calls the Cures Act legislation a “new world” where shared notes are valuable tools to improve communication between patients and physicians while strengthening their relationship. They cite evidence indicating that “when health professionals offer patients and families ready access to clinical notes, the quality and safety of care improves.”
Not all doctors are as enthusiastic. Many are concerned that patients might misinterpret what they see in their doctors’ notes, including complex descriptions of clinical assessments and decisions.
Others worry about patients having immediate access to their records, perhaps even before their physicians. The American Academy of Dermatology is working with the American Medical Association and other groups to gather real-world instances where the release of lab results, reports, or notes directly to patients before their physician could review the information with them caused emotional harm or other adverse consequences.
Undoubtedly, there are scenarios where unrestricted display of clinical notes could be problematic. One example is the issue of adolescents and reproductive health. Since parents now have access to their children’s records, some teenagers might hesitate to confide in their physicians and deny themselves important medical care.
The new rules permit blocking access to records if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or third parties. Psychotherapy counseling notes, for example, are completely exempt from the new requirements.
There are also state-level laws that can supersede the new federal law and block access to notes. For example, California law forbids providers from posting cancer test results without discussing them with the patient first.
Research indicates that shared notes have benefits that should outweigh the concerns of most physicians. One study showed that about 70% of patients said reviewing their notes helped them understand why medications were prescribed, which improved their compliance. This was particularly true for patients whose primary language is not English. A British study found that patients felt empowered by shared notes, and thought they improved their relationship with their physicians.
Other advantages of sharing notes include the ability of family members to review what happened at visits, which can be particularly important when dementia or other disabilities are involved. Patients will also be able to share their medical records with physicians outside of their health network, thus avoiding unnecessary or repetitious workups.
OpenNotes contends that when patients review their doctors’ notes, they gain “a newfound, deeper respect for what physicians have to understand to do their jobs.” Other predicted advantages include improved medical record accuracy and less miscommunication. In a study published in 2019 that evaluated experiences of patients who read ambulatory visit notes, only 5% were more worried after reading the notes and 3% were confused.
Alleviating worry among clinicians may be a bigger problem; but as a general principle, you should avoid judgmental language, and never write anything in a chart that you wouldn’t want your patients or their family members – or lawyers – to see.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
. While some clinicians consider it an unwelcome intrusion, advocates say it will improve communication and compliance.
Patient access to notes is not new. In many states, patients already have the ability to request copies of their charts, or to access truncated information via clinic websites. The difference is that most patients will now be able to click on a patient portal – such as MyChart, or other similar apps – and gain instantaneous, unfettered access to everything in their records.
Clinicians have traditionally thought of medical notes as private journal entries; but in the last few decades they have become an important component of the documentation necessary for billing, as well as evidence in the event of litigation. Now, with the implementation of the Cures Act, medical notes have evolved into a tool to communicate with the patient, rather than just among health care providers, lawyers, and billing departments.
Supporters contend that this change will make a big difference, because patients will be able to see exactly what their doctors have written, rather than just a list of confusing test results and diagnosis lists in “medicalese.”
OpenNotes, a think tank that has promoted the sharing of clinical notes with patients for years, calls the Cures Act legislation a “new world” where shared notes are valuable tools to improve communication between patients and physicians while strengthening their relationship. They cite evidence indicating that “when health professionals offer patients and families ready access to clinical notes, the quality and safety of care improves.”
Not all doctors are as enthusiastic. Many are concerned that patients might misinterpret what they see in their doctors’ notes, including complex descriptions of clinical assessments and decisions.
Others worry about patients having immediate access to their records, perhaps even before their physicians. The American Academy of Dermatology is working with the American Medical Association and other groups to gather real-world instances where the release of lab results, reports, or notes directly to patients before their physician could review the information with them caused emotional harm or other adverse consequences.
Undoubtedly, there are scenarios where unrestricted display of clinical notes could be problematic. One example is the issue of adolescents and reproductive health. Since parents now have access to their children’s records, some teenagers might hesitate to confide in their physicians and deny themselves important medical care.
The new rules permit blocking access to records if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or third parties. Psychotherapy counseling notes, for example, are completely exempt from the new requirements.
There are also state-level laws that can supersede the new federal law and block access to notes. For example, California law forbids providers from posting cancer test results without discussing them with the patient first.
Research indicates that shared notes have benefits that should outweigh the concerns of most physicians. One study showed that about 70% of patients said reviewing their notes helped them understand why medications were prescribed, which improved their compliance. This was particularly true for patients whose primary language is not English. A British study found that patients felt empowered by shared notes, and thought they improved their relationship with their physicians.
Other advantages of sharing notes include the ability of family members to review what happened at visits, which can be particularly important when dementia or other disabilities are involved. Patients will also be able to share their medical records with physicians outside of their health network, thus avoiding unnecessary or repetitious workups.
OpenNotes contends that when patients review their doctors’ notes, they gain “a newfound, deeper respect for what physicians have to understand to do their jobs.” Other predicted advantages include improved medical record accuracy and less miscommunication. In a study published in 2019 that evaluated experiences of patients who read ambulatory visit notes, only 5% were more worried after reading the notes and 3% were confused.
Alleviating worry among clinicians may be a bigger problem; but as a general principle, you should avoid judgmental language, and never write anything in a chart that you wouldn’t want your patients or their family members – or lawyers – to see.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
. While some clinicians consider it an unwelcome intrusion, advocates say it will improve communication and compliance.
Patient access to notes is not new. In many states, patients already have the ability to request copies of their charts, or to access truncated information via clinic websites. The difference is that most patients will now be able to click on a patient portal – such as MyChart, or other similar apps – and gain instantaneous, unfettered access to everything in their records.
Clinicians have traditionally thought of medical notes as private journal entries; but in the last few decades they have become an important component of the documentation necessary for billing, as well as evidence in the event of litigation. Now, with the implementation of the Cures Act, medical notes have evolved into a tool to communicate with the patient, rather than just among health care providers, lawyers, and billing departments.
Supporters contend that this change will make a big difference, because patients will be able to see exactly what their doctors have written, rather than just a list of confusing test results and diagnosis lists in “medicalese.”
OpenNotes, a think tank that has promoted the sharing of clinical notes with patients for years, calls the Cures Act legislation a “new world” where shared notes are valuable tools to improve communication between patients and physicians while strengthening their relationship. They cite evidence indicating that “when health professionals offer patients and families ready access to clinical notes, the quality and safety of care improves.”
Not all doctors are as enthusiastic. Many are concerned that patients might misinterpret what they see in their doctors’ notes, including complex descriptions of clinical assessments and decisions.
Others worry about patients having immediate access to their records, perhaps even before their physicians. The American Academy of Dermatology is working with the American Medical Association and other groups to gather real-world instances where the release of lab results, reports, or notes directly to patients before their physician could review the information with them caused emotional harm or other adverse consequences.
Undoubtedly, there are scenarios where unrestricted display of clinical notes could be problematic. One example is the issue of adolescents and reproductive health. Since parents now have access to their children’s records, some teenagers might hesitate to confide in their physicians and deny themselves important medical care.
The new rules permit blocking access to records if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or third parties. Psychotherapy counseling notes, for example, are completely exempt from the new requirements.
There are also state-level laws that can supersede the new federal law and block access to notes. For example, California law forbids providers from posting cancer test results without discussing them with the patient first.
Research indicates that shared notes have benefits that should outweigh the concerns of most physicians. One study showed that about 70% of patients said reviewing their notes helped them understand why medications were prescribed, which improved their compliance. This was particularly true for patients whose primary language is not English. A British study found that patients felt empowered by shared notes, and thought they improved their relationship with their physicians.
Other advantages of sharing notes include the ability of family members to review what happened at visits, which can be particularly important when dementia or other disabilities are involved. Patients will also be able to share their medical records with physicians outside of their health network, thus avoiding unnecessary or repetitious workups.
OpenNotes contends that when patients review their doctors’ notes, they gain “a newfound, deeper respect for what physicians have to understand to do their jobs.” Other predicted advantages include improved medical record accuracy and less miscommunication. In a study published in 2019 that evaluated experiences of patients who read ambulatory visit notes, only 5% were more worried after reading the notes and 3% were confused.
Alleviating worry among clinicians may be a bigger problem; but as a general principle, you should avoid judgmental language, and never write anything in a chart that you wouldn’t want your patients or their family members – or lawyers – to see.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
CLL patients: Diagnostic difficulties, treatment confusion with COVID-19
Chronic lymphocytic leukemia (CLL) patients present significant problems with regard to COVID-19 disease, according to a literature review by Yousef Roosta, MD, of Urmia (Iran) University of Medical Sciences, and colleagues.
Diagnostic interaction between CLL and COVID-19 provides a major challenge. CLL patients have a lower rate of anti–SARS-CoV-2 IgG development, and evidence shows worse therapeutic outcomes in these patients, according to study published in Leukemia Research Reports.
The researchers assessed 20 retrieved articles, 11 of which examined patients with CLL and with concomitant COVID-19; and 9 articles were designed as prospective or retrospective case series of such patients. The studies were assessed qualitatively by the QUADAS-2 tool.
Troubling results
Although the overall prevalence of CLL and COVID-19 concurrence was low, at 0.6% (95% confidence interval 0.5%-0.7%) according to the meta-analysis, the results showed some special challenges in the diagnosis and care of these patients.
Diagnostic difficulties are a unique problem. Lymphopenia is common in patients with COVID-19, while lymphocytosis may be considered a transient or even rare finding. The interplay between the two diseases is sometimes very misleading for specialists, and in patients with lymphocytosis, the diagnosis of CLL may be completely ignored, according to the researchers. They added that when performing a diagnostic approach for concurrent COVID-19 and CLL, due to differences in the amount and type of immune response, “relying on serological testing, and especially the evaluation of the anti–SARS-CoV-2 IgG levels may not be beneficial,” they indicated.
In addition, studies showed unacceptable therapeutic outcome in patients with concurrent CLL and COVID-19, with mortality ranging from 33% to 41.7%, showing a need to revise current treatment protocols, according to the authors. In one study, 85.7% of surviving patients showed a considerable decrease in functional class and significant fatigue, with such a poor prognosis occurring more commonly in the elderly.
With regard to treatment, “it is quite obvious that despite the use of current standard protocols, the prognosis of these patients will be much worse than the prognosis of CLL patients with no evidence of COVID-19. Even in the first-line treatment protocol for these patients, there is no agreement in combination therapy with selected CLL drugs along with management protocols of COVID-19 patients,” the researchers stated.
“[The] different hematological behaviors of two diseases might mimic the detection of COVID-19 in the CLL state and vise versa. Also, due to the low level of immune response against SARS-CoV-2 in CLL patients, both scheduled immunological-based diagnosis and treatment may fail,” the researchers added.
The authors reported that they had no disclosures.
Chronic lymphocytic leukemia (CLL) patients present significant problems with regard to COVID-19 disease, according to a literature review by Yousef Roosta, MD, of Urmia (Iran) University of Medical Sciences, and colleagues.
Diagnostic interaction between CLL and COVID-19 provides a major challenge. CLL patients have a lower rate of anti–SARS-CoV-2 IgG development, and evidence shows worse therapeutic outcomes in these patients, according to study published in Leukemia Research Reports.
The researchers assessed 20 retrieved articles, 11 of which examined patients with CLL and with concomitant COVID-19; and 9 articles were designed as prospective or retrospective case series of such patients. The studies were assessed qualitatively by the QUADAS-2 tool.
Troubling results
Although the overall prevalence of CLL and COVID-19 concurrence was low, at 0.6% (95% confidence interval 0.5%-0.7%) according to the meta-analysis, the results showed some special challenges in the diagnosis and care of these patients.
Diagnostic difficulties are a unique problem. Lymphopenia is common in patients with COVID-19, while lymphocytosis may be considered a transient or even rare finding. The interplay between the two diseases is sometimes very misleading for specialists, and in patients with lymphocytosis, the diagnosis of CLL may be completely ignored, according to the researchers. They added that when performing a diagnostic approach for concurrent COVID-19 and CLL, due to differences in the amount and type of immune response, “relying on serological testing, and especially the evaluation of the anti–SARS-CoV-2 IgG levels may not be beneficial,” they indicated.
In addition, studies showed unacceptable therapeutic outcome in patients with concurrent CLL and COVID-19, with mortality ranging from 33% to 41.7%, showing a need to revise current treatment protocols, according to the authors. In one study, 85.7% of surviving patients showed a considerable decrease in functional class and significant fatigue, with such a poor prognosis occurring more commonly in the elderly.
With regard to treatment, “it is quite obvious that despite the use of current standard protocols, the prognosis of these patients will be much worse than the prognosis of CLL patients with no evidence of COVID-19. Even in the first-line treatment protocol for these patients, there is no agreement in combination therapy with selected CLL drugs along with management protocols of COVID-19 patients,” the researchers stated.
“[The] different hematological behaviors of two diseases might mimic the detection of COVID-19 in the CLL state and vise versa. Also, due to the low level of immune response against SARS-CoV-2 in CLL patients, both scheduled immunological-based diagnosis and treatment may fail,” the researchers added.
The authors reported that they had no disclosures.
Chronic lymphocytic leukemia (CLL) patients present significant problems with regard to COVID-19 disease, according to a literature review by Yousef Roosta, MD, of Urmia (Iran) University of Medical Sciences, and colleagues.
Diagnostic interaction between CLL and COVID-19 provides a major challenge. CLL patients have a lower rate of anti–SARS-CoV-2 IgG development, and evidence shows worse therapeutic outcomes in these patients, according to study published in Leukemia Research Reports.
The researchers assessed 20 retrieved articles, 11 of which examined patients with CLL and with concomitant COVID-19; and 9 articles were designed as prospective or retrospective case series of such patients. The studies were assessed qualitatively by the QUADAS-2 tool.
Troubling results
Although the overall prevalence of CLL and COVID-19 concurrence was low, at 0.6% (95% confidence interval 0.5%-0.7%) according to the meta-analysis, the results showed some special challenges in the diagnosis and care of these patients.
Diagnostic difficulties are a unique problem. Lymphopenia is common in patients with COVID-19, while lymphocytosis may be considered a transient or even rare finding. The interplay between the two diseases is sometimes very misleading for specialists, and in patients with lymphocytosis, the diagnosis of CLL may be completely ignored, according to the researchers. They added that when performing a diagnostic approach for concurrent COVID-19 and CLL, due to differences in the amount and type of immune response, “relying on serological testing, and especially the evaluation of the anti–SARS-CoV-2 IgG levels may not be beneficial,” they indicated.
In addition, studies showed unacceptable therapeutic outcome in patients with concurrent CLL and COVID-19, with mortality ranging from 33% to 41.7%, showing a need to revise current treatment protocols, according to the authors. In one study, 85.7% of surviving patients showed a considerable decrease in functional class and significant fatigue, with such a poor prognosis occurring more commonly in the elderly.
With regard to treatment, “it is quite obvious that despite the use of current standard protocols, the prognosis of these patients will be much worse than the prognosis of CLL patients with no evidence of COVID-19. Even in the first-line treatment protocol for these patients, there is no agreement in combination therapy with selected CLL drugs along with management protocols of COVID-19 patients,” the researchers stated.
“[The] different hematological behaviors of two diseases might mimic the detection of COVID-19 in the CLL state and vise versa. Also, due to the low level of immune response against SARS-CoV-2 in CLL patients, both scheduled immunological-based diagnosis and treatment may fail,” the researchers added.
The authors reported that they had no disclosures.
FROM LEUKEMIA RESEARCH REPORTS
Unique oral drug candidate designed to overcome sickle cell disease
Progress is being made in the quest for an oral treatment for sickle cell disease. In preclinical trials, a new drug has shown the ability to induce blood cells to produce fetal hemoglobin at levels predicted to prevent sickling. The new small-molecule drug could be formulated into a convenient daily oral dosage, according to researchers who presented their results at the spring meeting of the American Chemical Society, which was held virtually.
The new drug candidate, designated FTX-6058 by Fulcrum Therapeutics, was developed using a proprietary small-molecule probe and CRISPR guide RNA libraries to screen “a disease-relevant cell model that allowed us to pinpoint a treatment target,” said Ivan V. Efremov, PhD, senior director, head of medicinal chemistry at the company, who presented the research.
Even though sickle cell patients carry genes leading to defective adult hemoglobin, they still carry stem cells in their bone marrow with the potential to produce fetal hemoglobin. FTX-6058 attaches to a protein inside these bone marrow stem cells destined to become mature red blood cells and reinstates their fetal hemoglobin expression, according to Dr. Efremov.
“What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” he explained, adding that if “some red blood cells did not express this, they could still sickle and cause disease symptoms.”
The premise behind the development of the drug evolved from the example of patients with sickle cell genes who also have a mutation that causes fetal hemoglobin production. The presence of fetal hemoglobin provides significant benefits to patients with sickle cell disease. At around 5%-10% levels of fetal hemoglobin expression, mortality is reduced. By 10%-25% levels of fetal hemoglobin, recurring events including vaso-occlusive crises, acute chest syndrome, and hospitalization are reduced. When fetal hemoglobin levels reaches around 25%-30%, enough red blood cell function is restored so that these patients become asymptomatic, Dr. Efremov said.
FTX-6058 was designed to mimic this effect.
FTX-6058 inhibits the action of the polycomb repressive complex 2 (PRC2) via binding to the EED subunit. PRC2 acts as a histone methyltransferase to control gene expression. Inhibition of PRC2 leads to significant fetal hemoglobin protein expression in both cell and mouse models. Other such inhibitors are under study for the suppression of cancer progression.
Preclinical experiments comparing FTX-6058 with the fetal hemoglobin booster, hydroxyurea, approved in the 1990s, showed the new drug candidate outperforms the current treatment, Christopher Moxham, PhD, chief scientific officer of Fulcrum Therapeutics, said in a company press release. The company began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments with FTX-6058 in human-derived cell assay systems and mouse models also showed an increase in fetal hemoglobin to meet the 25%-30% asymptomatic symptom threshold level.
Ongoing studies
The researchers plan to launch phase 2 clinical trial enrolling patients with sickle cell disease by end of 2021. In addition, further characterization of the therapeutic molecule is continuing, using genomics and additional cell assay systems to expand details FTX-6058’s mode of action.
The company also is looking to explore the use of FTX-6058 in patients with beta-thalassemia to supplement their reduced hemoglobin production.
The pharmacologic profile of FTX-6058 indicates that the drug has the potential to be administered as a once-a-day oral formulation, Dr. Efremov stated. Both the preclinical PK [pharmacokinetic] data and “the emerging PK from the human clinical study supports once-a-day oral administration, which obviously offers significant convenience to patients,” he added.
Fulcrum Therapeutics is funding the studies.
Progress is being made in the quest for an oral treatment for sickle cell disease. In preclinical trials, a new drug has shown the ability to induce blood cells to produce fetal hemoglobin at levels predicted to prevent sickling. The new small-molecule drug could be formulated into a convenient daily oral dosage, according to researchers who presented their results at the spring meeting of the American Chemical Society, which was held virtually.
The new drug candidate, designated FTX-6058 by Fulcrum Therapeutics, was developed using a proprietary small-molecule probe and CRISPR guide RNA libraries to screen “a disease-relevant cell model that allowed us to pinpoint a treatment target,” said Ivan V. Efremov, PhD, senior director, head of medicinal chemistry at the company, who presented the research.
Even though sickle cell patients carry genes leading to defective adult hemoglobin, they still carry stem cells in their bone marrow with the potential to produce fetal hemoglobin. FTX-6058 attaches to a protein inside these bone marrow stem cells destined to become mature red blood cells and reinstates their fetal hemoglobin expression, according to Dr. Efremov.
“What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” he explained, adding that if “some red blood cells did not express this, they could still sickle and cause disease symptoms.”
The premise behind the development of the drug evolved from the example of patients with sickle cell genes who also have a mutation that causes fetal hemoglobin production. The presence of fetal hemoglobin provides significant benefits to patients with sickle cell disease. At around 5%-10% levels of fetal hemoglobin expression, mortality is reduced. By 10%-25% levels of fetal hemoglobin, recurring events including vaso-occlusive crises, acute chest syndrome, and hospitalization are reduced. When fetal hemoglobin levels reaches around 25%-30%, enough red blood cell function is restored so that these patients become asymptomatic, Dr. Efremov said.
FTX-6058 was designed to mimic this effect.
FTX-6058 inhibits the action of the polycomb repressive complex 2 (PRC2) via binding to the EED subunit. PRC2 acts as a histone methyltransferase to control gene expression. Inhibition of PRC2 leads to significant fetal hemoglobin protein expression in both cell and mouse models. Other such inhibitors are under study for the suppression of cancer progression.
Preclinical experiments comparing FTX-6058 with the fetal hemoglobin booster, hydroxyurea, approved in the 1990s, showed the new drug candidate outperforms the current treatment, Christopher Moxham, PhD, chief scientific officer of Fulcrum Therapeutics, said in a company press release. The company began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments with FTX-6058 in human-derived cell assay systems and mouse models also showed an increase in fetal hemoglobin to meet the 25%-30% asymptomatic symptom threshold level.
Ongoing studies
The researchers plan to launch phase 2 clinical trial enrolling patients with sickle cell disease by end of 2021. In addition, further characterization of the therapeutic molecule is continuing, using genomics and additional cell assay systems to expand details FTX-6058’s mode of action.
The company also is looking to explore the use of FTX-6058 in patients with beta-thalassemia to supplement their reduced hemoglobin production.
The pharmacologic profile of FTX-6058 indicates that the drug has the potential to be administered as a once-a-day oral formulation, Dr. Efremov stated. Both the preclinical PK [pharmacokinetic] data and “the emerging PK from the human clinical study supports once-a-day oral administration, which obviously offers significant convenience to patients,” he added.
Fulcrum Therapeutics is funding the studies.
Progress is being made in the quest for an oral treatment for sickle cell disease. In preclinical trials, a new drug has shown the ability to induce blood cells to produce fetal hemoglobin at levels predicted to prevent sickling. The new small-molecule drug could be formulated into a convenient daily oral dosage, according to researchers who presented their results at the spring meeting of the American Chemical Society, which was held virtually.
The new drug candidate, designated FTX-6058 by Fulcrum Therapeutics, was developed using a proprietary small-molecule probe and CRISPR guide RNA libraries to screen “a disease-relevant cell model that allowed us to pinpoint a treatment target,” said Ivan V. Efremov, PhD, senior director, head of medicinal chemistry at the company, who presented the research.
Even though sickle cell patients carry genes leading to defective adult hemoglobin, they still carry stem cells in their bone marrow with the potential to produce fetal hemoglobin. FTX-6058 attaches to a protein inside these bone marrow stem cells destined to become mature red blood cells and reinstates their fetal hemoglobin expression, according to Dr. Efremov.
“What is really key is FTX-6058 upregulates fetal hemoglobin across all red blood cells, a pancellular distribution,” he explained, adding that if “some red blood cells did not express this, they could still sickle and cause disease symptoms.”
The premise behind the development of the drug evolved from the example of patients with sickle cell genes who also have a mutation that causes fetal hemoglobin production. The presence of fetal hemoglobin provides significant benefits to patients with sickle cell disease. At around 5%-10% levels of fetal hemoglobin expression, mortality is reduced. By 10%-25% levels of fetal hemoglobin, recurring events including vaso-occlusive crises, acute chest syndrome, and hospitalization are reduced. When fetal hemoglobin levels reaches around 25%-30%, enough red blood cell function is restored so that these patients become asymptomatic, Dr. Efremov said.
FTX-6058 was designed to mimic this effect.
FTX-6058 inhibits the action of the polycomb repressive complex 2 (PRC2) via binding to the EED subunit. PRC2 acts as a histone methyltransferase to control gene expression. Inhibition of PRC2 leads to significant fetal hemoglobin protein expression in both cell and mouse models. Other such inhibitors are under study for the suppression of cancer progression.
Preclinical experiments comparing FTX-6058 with the fetal hemoglobin booster, hydroxyurea, approved in the 1990s, showed the new drug candidate outperforms the current treatment, Christopher Moxham, PhD, chief scientific officer of Fulcrum Therapeutics, said in a company press release. The company began a phase 1 safety trial in healthy adult volunteers last year after preclinical experiments with FTX-6058 in human-derived cell assay systems and mouse models also showed an increase in fetal hemoglobin to meet the 25%-30% asymptomatic symptom threshold level.
Ongoing studies
The researchers plan to launch phase 2 clinical trial enrolling patients with sickle cell disease by end of 2021. In addition, further characterization of the therapeutic molecule is continuing, using genomics and additional cell assay systems to expand details FTX-6058’s mode of action.
The company also is looking to explore the use of FTX-6058 in patients with beta-thalassemia to supplement their reduced hemoglobin production.
The pharmacologic profile of FTX-6058 indicates that the drug has the potential to be administered as a once-a-day oral formulation, Dr. Efremov stated. Both the preclinical PK [pharmacokinetic] data and “the emerging PK from the human clinical study supports once-a-day oral administration, which obviously offers significant convenience to patients,” he added.
Fulcrum Therapeutics is funding the studies.
Blacks and Hispanics have higher inpatient use for mycosis fungoides
according to an analysis of the 2012-2017 National Inpatient Sample (NIS).
The findings are consistent with prior studies implicating earlier and more severe disease in Black and Hispanic patients, and reinforce the importance of accurate diagnosis and early treatment.
Dermatologists should maintain “a higher index of suspicion for MF in patients with skin of color, as early diagnosis may help mitigate the downstream costs of management,” Justin Choi, BA, a medical student at the University of Illinois at Chicago, said at the annual Skin of Color Society symposium.
Mr. Choi and coinvestigators, led by Shawn Kwatra, MD, of Johns Hopkins University, Baltimore, identified hospital admissions for MF in the NIS for 10,790 White patients, 4,020 Black patients, and 1,615 Hispanic patients over the 5-year period. The inpatient prevalence of MF – the most common variant of primary cutaneous T-cell lymphoma – was highest in these groups.
Black and Hispanic patients who were hospitalized for MF were significantly younger than White patients, with a mean age of 51.7 years and 48.5 years, respectively, compared with 59.9 years (P < .001 in each case). They also had longer lengths of stay: 8.34 days on average for Black patients and 8.88 for Hispanic patients, compared with 6.66 days for White patients (P < .001 and P = .001, respectively).
Hispanic patients accrued the highest costs of care (a mean of $107,242 vs. $64,049, P =.003) and underwent more procedures (a mean of 2.43 vs. 1.93, P = .004) than White patients. Black patients similarly had higher costs associated with their hospital stay (a mean of $75,053 vs. $64,049, P =.042).
In a multivariate linear regression adjusted for age, sex and insurance type, Black race remained significantly associated with a longer LOS than White race, and Hispanic ethnicity with a longer LOS, increased costs, and more procedures than White race.
The NIS is a publicly available, all-payer inpatient care database developed for the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project.
Mr. Choi is a dermatology research fellow working under the guidance of Dr. Kwatra.
according to an analysis of the 2012-2017 National Inpatient Sample (NIS).
The findings are consistent with prior studies implicating earlier and more severe disease in Black and Hispanic patients, and reinforce the importance of accurate diagnosis and early treatment.
Dermatologists should maintain “a higher index of suspicion for MF in patients with skin of color, as early diagnosis may help mitigate the downstream costs of management,” Justin Choi, BA, a medical student at the University of Illinois at Chicago, said at the annual Skin of Color Society symposium.
Mr. Choi and coinvestigators, led by Shawn Kwatra, MD, of Johns Hopkins University, Baltimore, identified hospital admissions for MF in the NIS for 10,790 White patients, 4,020 Black patients, and 1,615 Hispanic patients over the 5-year period. The inpatient prevalence of MF – the most common variant of primary cutaneous T-cell lymphoma – was highest in these groups.
Black and Hispanic patients who were hospitalized for MF were significantly younger than White patients, with a mean age of 51.7 years and 48.5 years, respectively, compared with 59.9 years (P < .001 in each case). They also had longer lengths of stay: 8.34 days on average for Black patients and 8.88 for Hispanic patients, compared with 6.66 days for White patients (P < .001 and P = .001, respectively).
Hispanic patients accrued the highest costs of care (a mean of $107,242 vs. $64,049, P =.003) and underwent more procedures (a mean of 2.43 vs. 1.93, P = .004) than White patients. Black patients similarly had higher costs associated with their hospital stay (a mean of $75,053 vs. $64,049, P =.042).
In a multivariate linear regression adjusted for age, sex and insurance type, Black race remained significantly associated with a longer LOS than White race, and Hispanic ethnicity with a longer LOS, increased costs, and more procedures than White race.
The NIS is a publicly available, all-payer inpatient care database developed for the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project.
Mr. Choi is a dermatology research fellow working under the guidance of Dr. Kwatra.
according to an analysis of the 2012-2017 National Inpatient Sample (NIS).
The findings are consistent with prior studies implicating earlier and more severe disease in Black and Hispanic patients, and reinforce the importance of accurate diagnosis and early treatment.
Dermatologists should maintain “a higher index of suspicion for MF in patients with skin of color, as early diagnosis may help mitigate the downstream costs of management,” Justin Choi, BA, a medical student at the University of Illinois at Chicago, said at the annual Skin of Color Society symposium.
Mr. Choi and coinvestigators, led by Shawn Kwatra, MD, of Johns Hopkins University, Baltimore, identified hospital admissions for MF in the NIS for 10,790 White patients, 4,020 Black patients, and 1,615 Hispanic patients over the 5-year period. The inpatient prevalence of MF – the most common variant of primary cutaneous T-cell lymphoma – was highest in these groups.
Black and Hispanic patients who were hospitalized for MF were significantly younger than White patients, with a mean age of 51.7 years and 48.5 years, respectively, compared with 59.9 years (P < .001 in each case). They also had longer lengths of stay: 8.34 days on average for Black patients and 8.88 for Hispanic patients, compared with 6.66 days for White patients (P < .001 and P = .001, respectively).
Hispanic patients accrued the highest costs of care (a mean of $107,242 vs. $64,049, P =.003) and underwent more procedures (a mean of 2.43 vs. 1.93, P = .004) than White patients. Black patients similarly had higher costs associated with their hospital stay (a mean of $75,053 vs. $64,049, P =.042).
In a multivariate linear regression adjusted for age, sex and insurance type, Black race remained significantly associated with a longer LOS than White race, and Hispanic ethnicity with a longer LOS, increased costs, and more procedures than White race.
The NIS is a publicly available, all-payer inpatient care database developed for the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project.
Mr. Choi is a dermatology research fellow working under the guidance of Dr. Kwatra.
FROM SOC SOCIETY 2021