User login
Prophylactic NPWT may not improve complication rate after gynecologic surgery
Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research published in Obstetrics & Gynecology.
“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” wrote Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues.
Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecologic surgery between March 2016 and August 2019.
The median age of the patients was 61 years and median BMI was 26 kg/m2. Thirty-two patients with a BMI of 40 kg/m2 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.
In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.
The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%) compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5-6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”
The analysis of patients with a BMI of 40 kg/m2 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) did so in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 kg/m2 (range, 17-60 kg/m2) was significantly associated with not developing a wound complication compared with a BMI of 32 kg/m2 (range, 17-56 kg/m2) (P < .001), and that 41% of patients with a BMI of at least 40 kg/m2 experienced wound complications compared with 15% of patients with a BMI of less than 40 kg/m2 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% confidence interval, 1.06–1.14).
Applicability of results unclear for patients with higher BMI
Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.
“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, noting the median BMI of 26 kg/m2 for patients included in the study. A study that included only patients with a BMI of 40 kg/m2 or higher “would have made these results more applicable,” she said.
The low rate of wound complications in the study could be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29 kg/m2 compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67 kg/m2.
“It’s hard to cross trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical site infections and wound complications in the heavy patient with comorbidities is still unanswered.”
The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”
This study was funded in part by a support grant from NIH/NCI Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speakers bureau positions with AstraZeneca, Biom’Up, Bovie Medical Co., C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical Inc., JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix Inc., UpToDate, and Verthermia Inc. Dr. Temkin reported no relevant financial disclosures.
Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research published in Obstetrics & Gynecology.
“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” wrote Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues.
Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecologic surgery between March 2016 and August 2019.
The median age of the patients was 61 years and median BMI was 26 kg/m2. Thirty-two patients with a BMI of 40 kg/m2 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.
In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.
The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%) compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5-6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”
The analysis of patients with a BMI of 40 kg/m2 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) did so in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 kg/m2 (range, 17-60 kg/m2) was significantly associated with not developing a wound complication compared with a BMI of 32 kg/m2 (range, 17-56 kg/m2) (P < .001), and that 41% of patients with a BMI of at least 40 kg/m2 experienced wound complications compared with 15% of patients with a BMI of less than 40 kg/m2 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% confidence interval, 1.06–1.14).
Applicability of results unclear for patients with higher BMI
Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.
“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, noting the median BMI of 26 kg/m2 for patients included in the study. A study that included only patients with a BMI of 40 kg/m2 or higher “would have made these results more applicable,” she said.
The low rate of wound complications in the study could be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29 kg/m2 compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67 kg/m2.
“It’s hard to cross trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical site infections and wound complications in the heavy patient with comorbidities is still unanswered.”
The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”
This study was funded in part by a support grant from NIH/NCI Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speakers bureau positions with AstraZeneca, Biom’Up, Bovie Medical Co., C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical Inc., JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix Inc., UpToDate, and Verthermia Inc. Dr. Temkin reported no relevant financial disclosures.
Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research published in Obstetrics & Gynecology.
“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” wrote Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues.
Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecologic surgery between March 2016 and August 2019.
The median age of the patients was 61 years and median BMI was 26 kg/m2. Thirty-two patients with a BMI of 40 kg/m2 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.
In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.
The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%) compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5-6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”
The analysis of patients with a BMI of 40 kg/m2 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) did so in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 kg/m2 (range, 17-60 kg/m2) was significantly associated with not developing a wound complication compared with a BMI of 32 kg/m2 (range, 17-56 kg/m2) (P < .001), and that 41% of patients with a BMI of at least 40 kg/m2 experienced wound complications compared with 15% of patients with a BMI of less than 40 kg/m2 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% confidence interval, 1.06–1.14).
Applicability of results unclear for patients with higher BMI
Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.
“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, noting the median BMI of 26 kg/m2 for patients included in the study. A study that included only patients with a BMI of 40 kg/m2 or higher “would have made these results more applicable,” she said.
The low rate of wound complications in the study could be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29 kg/m2 compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67 kg/m2.
“It’s hard to cross trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical site infections and wound complications in the heavy patient with comorbidities is still unanswered.”
The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”
This study was funded in part by a support grant from NIH/NCI Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speakers bureau positions with AstraZeneca, Biom’Up, Bovie Medical Co., C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical Inc., JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix Inc., UpToDate, and Verthermia Inc. Dr. Temkin reported no relevant financial disclosures.
FROM OBSTETRICS & GYNECOLOGY
Women and ACS: Focus on typical symptoms to improve outcomes
There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.
“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
Sexes share key symptoms, but not treatment
Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.
There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.
Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.
In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.
“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
Additional symptoms may muddy the diagnostic waters
In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.
In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.
In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).
There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
‘Yentl syndrome’ persists
“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.
Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.
This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.
The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.
“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.
The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.
“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
Sexes share key symptoms, but not treatment
Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.
There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.
Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.
In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.
“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
Additional symptoms may muddy the diagnostic waters
In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.
In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.
In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).
There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
‘Yentl syndrome’ persists
“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.
Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.
This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.
The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.
“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.
The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
There are some differences in how women relative to men report symptoms of an acute coronary syndrome (ACS), but they should not be permitted to get in the way of prompt diagnosis and treatment, according to an expert review at the virtual Going Back to the Heart of Cardiology meeting.
“We need to get away from the idea that symptoms of a myocardial infarction in women are atypical, because women are also having typical symptoms,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix.
Sexes share key symptoms, but not treatment
Although “women are more likely to report additional symptoms,” chest pain “is pretty much equal between men and women” presenting with an ACS, according to Dr. Gulati.
There are several studies that have shown this, including the Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO). In VIRGO, which looked at ACS symptom presentation in younger patients (ages 18-55 years), 87.0% of women versus 89.5% of men presented with chest pain defined as pain, pressure, tightness, or discomfort.
Even among those who recognize that more women die of cardiovascular disease (CVD) disease than any other cause, nothing seems to erase the bias that women in an ED are less likely than men to be having a heart attack. About 60 million women in the United States have CVD, so no threat imposes a higher toll in morbidity and mortality.
In comparison, there are only about 3.5 million women with breast cancer. Even though this is a major cause of morbidity and mortality in women, it is dwarfed by CVD, according to statistics cited by Dr. Gulati. Yet, the data show women get inferior care by guideline-based standards.
“After a myocardial infarction, women relative to men are less likely to get aspirin or beta-blockers within 24 hours, they are less likely to undergo any type of invasive procedure, and they are less likely to meet the door-to-balloon time or receive any reperfusion therapy,” Dr. Gulati said. After a CVD event, “the only thing women do better is to die.”
Additional symptoms may muddy the diagnostic waters
In the setting of ACS, the problem is not that women fail to report symptoms that should lead clinicians to consider CVD, but that they report additional symptoms. For the clinician less inclined to consider CVD in women, particularly younger women, there is a greater risk of going down the wrong diagnostic pathway.
In other words, women report symptoms consistent with CVD, “but it is a question of whether we are hearing it,” Dr. Gulati said.
In the VIRGO study, 61.9% of women versus 54.8% of men (P < .001) presented three or more symptoms in addition to chest pain, such as epigastric symptoms, discomfort in the arms or neck, or palpitations. Women were more likely than men to attribute the symptoms to stress or anxiety (20.9% vs. 11.8%; P < .001), while less likely to consider them a result of muscle pain (15.4% vs. 21.2%; P = .029).
There are other gender differences for ACS. For example, women are more likely than men to presented ischemia without obstruction, but Dr. Gulati emphasized that lack of obstruction is not a reason to dismiss the potential for an underlying CV cause.
‘Yentl syndrome’ persists
“Women should not need to present exactly like men to be taken seriously,” she said, describing the “Yentl syndrome,” which now has its own Wikipedia page. A cardiovascular version of this syndrome was first described 30 years ago. Based on a movie of a woman who cross dresses in order to be allowed to undertake Jewish studies, the term captures the societal failure to adapt care for women who do not present disease the same way that men do.
Overall, inadequate urgency to pursue potential symptoms of ACS in women is just another manifestation of the “bikini approach to women’s health,” according to Dr. Gulati. This describes the focus on the breast and reproductive system to the exclusion or other organs and anatomy. Dr. Gulati speculated that this might be the reason that clinicians have failed to apply ACS guidelines to women with the same rigor that they apply to men.
This is hardly a new issue. Calls for improving cardiovascular care in women have been increasing in volume for more than past 20 years, but the issue has proven persistent, according to Dr. Gulati. As an example, she noted that the same types of gaps in care and in outcome reported in a 2008 registry study had not much changed in an article published 8 years later.
The solution is not complex, according to Dr. Gulati. In the ED, guideline-directed diagnostic tests should be offered to any man or woman, including younger women, who present with chest pain, ignoring gender bias that threatens misinterpretation of patient history and symptoms. Once CVD is diagnosed as promptly in women as it is in men, guideline-directed intervention would be expected to reduce the gender gap in outcomes.
“By applying standardized protocols, it will help us to the same for women as we do for men,” Dr. Gulati said.
The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
FROM GOING BACK TO THE HEART OF CARDIOLOGY
Lifestyle coaching for obesity associated with improved cardiometabolic numbers in study
Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.
The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .
“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”
In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.
Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
Cholesterol changes in intervention vs. control group
HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).
Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.
There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
Funding barriers to obesity treatment
The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.
“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.
John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.
“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.
That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.
“You don’t necessarily need to be a physician to do this,” Dr. Flack said.
For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.
“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.
Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.
“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.
A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”
Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.
The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .
“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”
In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.
Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
Cholesterol changes in intervention vs. control group
HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).
Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.
There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
Funding barriers to obesity treatment
The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.
“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.
John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.
“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.
That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.
“You don’t necessarily need to be a physician to do this,” Dr. Flack said.
For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.
“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.
Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.
“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.
A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”
Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.
The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .
“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”
In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.
Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
Cholesterol changes in intervention vs. control group
HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).
Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.
There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
Funding barriers to obesity treatment
The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.
“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.
John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.
“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.
That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.
“You don’t necessarily need to be a physician to do this,” Dr. Flack said.
For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.
“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.
Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.
“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.
A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”
Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
Combo disappoints in metastatic, castration-resistant prostate cancer
In a phase 1/2 study, adding saracatinib to docetaxel increased toxicity without improving progression-free or overall survival.
“Although we could safely combine the Src kinase inhibitor saracatinib with docetaxel, it did not show any improvement in outcomes, when compared with docetaxel plus placebo. We therefore do not recommend proceeding to a phase 3 trial,” said investigator Robert J. Jones, MD, PhD, of the Institute of Cancer Sciences at the University of Glasgow, Scotland.
Dr. Jones presented the phase 1/2 trial results at the 2021 Genitourinary Cancers Symposium (Abstract 107).
He explained that saracatinib targets Src family members, and Src activity is increased during the acquisition of castration resistance and during taxane resistance. Dr. Jones and colleagues therefore theorized that saracatinib could be beneficial for patients with mCRPC.
The team tested their theory with the phase 1/2 trial, enrolling patients with mCRPC who had not previously received taxanes or radionucleotides. Dr. Jones reported results for 10 patients in the phase 1 portion of the trial and 140 patients in the phase 2 portion.
In phase 1, patients received saracatinib at 50 mg, 125 mg, or 175 mg daily plus docetaxel at 75 mg/m2.
There were no dose-limiting toxicities or pharmacokinetic interactions in these patients, so the phase 2 dose of saracatinib was 175 mg daily.
In phase 2, patients were randomized to receive saracatinib plus docetaxel or placebo plus docetaxel.
Results: Safety and efficacy
“In terms of efficacy, the trial failed to meet its primary endpoint of demonstrating an improvement in progression-free survival. Indeed, there was a trend toward an improvement in progression-free survival for patients receiving placebo,” Dr. Jones said. “Similarly, in this key secondary endpoint of overall survival, there was no benefit from the addition of saracatinib. And again, there was a trend toward an improved survival in patients receiving placebo.”
The median progression-free survival was 19 weeks with saracatinib and 29 weeks with placebo (adjusted hazard ratio, 1.348).
The median overall survival was 62 weeks with saracatinib and 83 weeks with placebo (adjusted HR, 1.422).
Furthermore, there were no significant differences between the treatment arms for two other efficacy endpoints – maximum absolute change in prostate-specific antigen levels and absolute change in circulating tumor cell count from baseline to cycle three.
However, grade 3 or higher adverse events were more common in the saracatinib arm than in the placebo arm – 59% (41/69) and 41% (29/71), respectively.
The most common grade 3 or higher adverse events (in the saracatinib and placebo arms, respectively) were neutropenia (25% vs. 8%), diarrhea (12% vs. 4%), and fatigue (6% vs. 4%).
This research was funded by the UK National Health Service and Cancer Research UK. Dr. Jones disclosed relationships with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, and a number of other companies.
In a phase 1/2 study, adding saracatinib to docetaxel increased toxicity without improving progression-free or overall survival.
“Although we could safely combine the Src kinase inhibitor saracatinib with docetaxel, it did not show any improvement in outcomes, when compared with docetaxel plus placebo. We therefore do not recommend proceeding to a phase 3 trial,” said investigator Robert J. Jones, MD, PhD, of the Institute of Cancer Sciences at the University of Glasgow, Scotland.
Dr. Jones presented the phase 1/2 trial results at the 2021 Genitourinary Cancers Symposium (Abstract 107).
He explained that saracatinib targets Src family members, and Src activity is increased during the acquisition of castration resistance and during taxane resistance. Dr. Jones and colleagues therefore theorized that saracatinib could be beneficial for patients with mCRPC.
The team tested their theory with the phase 1/2 trial, enrolling patients with mCRPC who had not previously received taxanes or radionucleotides. Dr. Jones reported results for 10 patients in the phase 1 portion of the trial and 140 patients in the phase 2 portion.
In phase 1, patients received saracatinib at 50 mg, 125 mg, or 175 mg daily plus docetaxel at 75 mg/m2.
There were no dose-limiting toxicities or pharmacokinetic interactions in these patients, so the phase 2 dose of saracatinib was 175 mg daily.
In phase 2, patients were randomized to receive saracatinib plus docetaxel or placebo plus docetaxel.
Results: Safety and efficacy
“In terms of efficacy, the trial failed to meet its primary endpoint of demonstrating an improvement in progression-free survival. Indeed, there was a trend toward an improvement in progression-free survival for patients receiving placebo,” Dr. Jones said. “Similarly, in this key secondary endpoint of overall survival, there was no benefit from the addition of saracatinib. And again, there was a trend toward an improved survival in patients receiving placebo.”
The median progression-free survival was 19 weeks with saracatinib and 29 weeks with placebo (adjusted hazard ratio, 1.348).
The median overall survival was 62 weeks with saracatinib and 83 weeks with placebo (adjusted HR, 1.422).
Furthermore, there were no significant differences between the treatment arms for two other efficacy endpoints – maximum absolute change in prostate-specific antigen levels and absolute change in circulating tumor cell count from baseline to cycle three.
However, grade 3 or higher adverse events were more common in the saracatinib arm than in the placebo arm – 59% (41/69) and 41% (29/71), respectively.
The most common grade 3 or higher adverse events (in the saracatinib and placebo arms, respectively) were neutropenia (25% vs. 8%), diarrhea (12% vs. 4%), and fatigue (6% vs. 4%).
This research was funded by the UK National Health Service and Cancer Research UK. Dr. Jones disclosed relationships with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, and a number of other companies.
In a phase 1/2 study, adding saracatinib to docetaxel increased toxicity without improving progression-free or overall survival.
“Although we could safely combine the Src kinase inhibitor saracatinib with docetaxel, it did not show any improvement in outcomes, when compared with docetaxel plus placebo. We therefore do not recommend proceeding to a phase 3 trial,” said investigator Robert J. Jones, MD, PhD, of the Institute of Cancer Sciences at the University of Glasgow, Scotland.
Dr. Jones presented the phase 1/2 trial results at the 2021 Genitourinary Cancers Symposium (Abstract 107).
He explained that saracatinib targets Src family members, and Src activity is increased during the acquisition of castration resistance and during taxane resistance. Dr. Jones and colleagues therefore theorized that saracatinib could be beneficial for patients with mCRPC.
The team tested their theory with the phase 1/2 trial, enrolling patients with mCRPC who had not previously received taxanes or radionucleotides. Dr. Jones reported results for 10 patients in the phase 1 portion of the trial and 140 patients in the phase 2 portion.
In phase 1, patients received saracatinib at 50 mg, 125 mg, or 175 mg daily plus docetaxel at 75 mg/m2.
There were no dose-limiting toxicities or pharmacokinetic interactions in these patients, so the phase 2 dose of saracatinib was 175 mg daily.
In phase 2, patients were randomized to receive saracatinib plus docetaxel or placebo plus docetaxel.
Results: Safety and efficacy
“In terms of efficacy, the trial failed to meet its primary endpoint of demonstrating an improvement in progression-free survival. Indeed, there was a trend toward an improvement in progression-free survival for patients receiving placebo,” Dr. Jones said. “Similarly, in this key secondary endpoint of overall survival, there was no benefit from the addition of saracatinib. And again, there was a trend toward an improved survival in patients receiving placebo.”
The median progression-free survival was 19 weeks with saracatinib and 29 weeks with placebo (adjusted hazard ratio, 1.348).
The median overall survival was 62 weeks with saracatinib and 83 weeks with placebo (adjusted HR, 1.422).
Furthermore, there were no significant differences between the treatment arms for two other efficacy endpoints – maximum absolute change in prostate-specific antigen levels and absolute change in circulating tumor cell count from baseline to cycle three.
However, grade 3 or higher adverse events were more common in the saracatinib arm than in the placebo arm – 59% (41/69) and 41% (29/71), respectively.
The most common grade 3 or higher adverse events (in the saracatinib and placebo arms, respectively) were neutropenia (25% vs. 8%), diarrhea (12% vs. 4%), and fatigue (6% vs. 4%).
This research was funded by the UK National Health Service and Cancer Research UK. Dr. Jones disclosed relationships with Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, and a number of other companies.
FROM GUCS 2021
COVID-19 studies funded by rheumatology foundation
Five lines of research related to COVID-19 and people with rheumatic diseases will be explored with $1.65 million awarded recently by the Rheumatology Research Foundation.
Investigators will explore topics ranging from respiratory health to telemedicine with the awards, given by the foundation that is the largest private funding source for rheumatology research and training in the United States. The projects are an attempt to deepen the understanding about how people with rheumatic illnesses are affected by COVID-19.
“Our current understanding of why there are differences in severity of COVID-19 illness among rheumatology patients is limited,” Foundation President S. Louis Bridges, MD, PhD, said. “Additionally, there are many other gaps in our knowledge of the clinical aspects of SARS-CoV-2 infection in patients with rheumatic diseases, and how the pandemic has changed health care delivery. There is an urgent need to acquire new knowledge on COVID-19 in patients with [rheumatic and musculoskeletal diseases].”
These are the research projects funded:
- Scientist Development Award: Respiratory complications of coronavirus disease (COVID-19) in rheumatic diseases, led by Kristin D’Silva, MD, of Massachusetts General Hospital in Boston (3-year, $225,000 grant)
- Scientist Development Award: COVID-19 in patients with inflammatory arthritis: A prospective study on the effects of immunomodulatory therapy on susceptibility and clinical outcomes, by Rebecca Haberman, MD, of New York University (3-year, $225,000 grant)
- Innovative Research Award: Antiphospholipid antibodies in COVID-19, led by Jason Knight, MD, PhD, of the University of Michigan, Ann Arbor (2-year, $400,000 grant);
- Innovative Research Award: Effectiveness of telerheumatology for delivering high-quality rheumatology care during the COVID-19 crisis, led by Maria Danila, MD, MSc, MSPH, of University of Alabama at Birmingham (2-year, $400,000 grant)
- Norman B. Gaylis, MD, Clinical Research Award: Telehealth-delivered health care to improve care (THRIVE) in community-practice rheumatology, led by Swamy Venuturupalli, MD, of Beverly Hills, Calif.–based Attune Health (2-year, $400,000 grant)
Dr. Bridges said the foundation accepted submissions in basic science, translational science, clinical science, health services research, and patient- and practice-centered research.
“What differentiates these studies from our existing awards portfolio is they all explore the relationships between rheumatic and musculoskeletal diseases and SARS-CoV-2,” he said. “Ultimately, the outcomes of these projects will contribute to a more comprehensive knowledge base and advance avenues of patient care in the COVID-19 pandemic.”
Dr. Gaylis, a rheumatologist in private practice in Aventura, Fla., said he was pleased that a telehealth project was chosen as the award given in his name.
“From a COVID point of view, this has been extremely valuable in allowing us to continue to help out patients, connect with our patients, provide them treatment, even if it’s not hands on, at least guide them in how to deal with their chronic rheumatic illnesses,” he said.
This line of research can also help explore the feasibility of telemedicine in helping meet the needs of rural communities facing shortages of rheumatologists.
“Can telemedicine provide a source of rheumatologic access for people who really don’t have a live provider in close proximity?” he said. “I think that’s really why this particular award is very, very timely.”
“It’s so difficult for clinicians to get funding for their research, for their ideas and for the discoveries they were making on a day-to-day basis while they were practicing in a clinical community environment,” he said. “So for me it was really something that inspired me to really create this award.”
Five lines of research related to COVID-19 and people with rheumatic diseases will be explored with $1.65 million awarded recently by the Rheumatology Research Foundation.
Investigators will explore topics ranging from respiratory health to telemedicine with the awards, given by the foundation that is the largest private funding source for rheumatology research and training in the United States. The projects are an attempt to deepen the understanding about how people with rheumatic illnesses are affected by COVID-19.
“Our current understanding of why there are differences in severity of COVID-19 illness among rheumatology patients is limited,” Foundation President S. Louis Bridges, MD, PhD, said. “Additionally, there are many other gaps in our knowledge of the clinical aspects of SARS-CoV-2 infection in patients with rheumatic diseases, and how the pandemic has changed health care delivery. There is an urgent need to acquire new knowledge on COVID-19 in patients with [rheumatic and musculoskeletal diseases].”
These are the research projects funded:
- Scientist Development Award: Respiratory complications of coronavirus disease (COVID-19) in rheumatic diseases, led by Kristin D’Silva, MD, of Massachusetts General Hospital in Boston (3-year, $225,000 grant)
- Scientist Development Award: COVID-19 in patients with inflammatory arthritis: A prospective study on the effects of immunomodulatory therapy on susceptibility and clinical outcomes, by Rebecca Haberman, MD, of New York University (3-year, $225,000 grant)
- Innovative Research Award: Antiphospholipid antibodies in COVID-19, led by Jason Knight, MD, PhD, of the University of Michigan, Ann Arbor (2-year, $400,000 grant);
- Innovative Research Award: Effectiveness of telerheumatology for delivering high-quality rheumatology care during the COVID-19 crisis, led by Maria Danila, MD, MSc, MSPH, of University of Alabama at Birmingham (2-year, $400,000 grant)
- Norman B. Gaylis, MD, Clinical Research Award: Telehealth-delivered health care to improve care (THRIVE) in community-practice rheumatology, led by Swamy Venuturupalli, MD, of Beverly Hills, Calif.–based Attune Health (2-year, $400,000 grant)
Dr. Bridges said the foundation accepted submissions in basic science, translational science, clinical science, health services research, and patient- and practice-centered research.
“What differentiates these studies from our existing awards portfolio is they all explore the relationships between rheumatic and musculoskeletal diseases and SARS-CoV-2,” he said. “Ultimately, the outcomes of these projects will contribute to a more comprehensive knowledge base and advance avenues of patient care in the COVID-19 pandemic.”
Dr. Gaylis, a rheumatologist in private practice in Aventura, Fla., said he was pleased that a telehealth project was chosen as the award given in his name.
“From a COVID point of view, this has been extremely valuable in allowing us to continue to help out patients, connect with our patients, provide them treatment, even if it’s not hands on, at least guide them in how to deal with their chronic rheumatic illnesses,” he said.
This line of research can also help explore the feasibility of telemedicine in helping meet the needs of rural communities facing shortages of rheumatologists.
“Can telemedicine provide a source of rheumatologic access for people who really don’t have a live provider in close proximity?” he said. “I think that’s really why this particular award is very, very timely.”
“It’s so difficult for clinicians to get funding for their research, for their ideas and for the discoveries they were making on a day-to-day basis while they were practicing in a clinical community environment,” he said. “So for me it was really something that inspired me to really create this award.”
Five lines of research related to COVID-19 and people with rheumatic diseases will be explored with $1.65 million awarded recently by the Rheumatology Research Foundation.
Investigators will explore topics ranging from respiratory health to telemedicine with the awards, given by the foundation that is the largest private funding source for rheumatology research and training in the United States. The projects are an attempt to deepen the understanding about how people with rheumatic illnesses are affected by COVID-19.
“Our current understanding of why there are differences in severity of COVID-19 illness among rheumatology patients is limited,” Foundation President S. Louis Bridges, MD, PhD, said. “Additionally, there are many other gaps in our knowledge of the clinical aspects of SARS-CoV-2 infection in patients with rheumatic diseases, and how the pandemic has changed health care delivery. There is an urgent need to acquire new knowledge on COVID-19 in patients with [rheumatic and musculoskeletal diseases].”
These are the research projects funded:
- Scientist Development Award: Respiratory complications of coronavirus disease (COVID-19) in rheumatic diseases, led by Kristin D’Silva, MD, of Massachusetts General Hospital in Boston (3-year, $225,000 grant)
- Scientist Development Award: COVID-19 in patients with inflammatory arthritis: A prospective study on the effects of immunomodulatory therapy on susceptibility and clinical outcomes, by Rebecca Haberman, MD, of New York University (3-year, $225,000 grant)
- Innovative Research Award: Antiphospholipid antibodies in COVID-19, led by Jason Knight, MD, PhD, of the University of Michigan, Ann Arbor (2-year, $400,000 grant);
- Innovative Research Award: Effectiveness of telerheumatology for delivering high-quality rheumatology care during the COVID-19 crisis, led by Maria Danila, MD, MSc, MSPH, of University of Alabama at Birmingham (2-year, $400,000 grant)
- Norman B. Gaylis, MD, Clinical Research Award: Telehealth-delivered health care to improve care (THRIVE) in community-practice rheumatology, led by Swamy Venuturupalli, MD, of Beverly Hills, Calif.–based Attune Health (2-year, $400,000 grant)
Dr. Bridges said the foundation accepted submissions in basic science, translational science, clinical science, health services research, and patient- and practice-centered research.
“What differentiates these studies from our existing awards portfolio is they all explore the relationships between rheumatic and musculoskeletal diseases and SARS-CoV-2,” he said. “Ultimately, the outcomes of these projects will contribute to a more comprehensive knowledge base and advance avenues of patient care in the COVID-19 pandemic.”
Dr. Gaylis, a rheumatologist in private practice in Aventura, Fla., said he was pleased that a telehealth project was chosen as the award given in his name.
“From a COVID point of view, this has been extremely valuable in allowing us to continue to help out patients, connect with our patients, provide them treatment, even if it’s not hands on, at least guide them in how to deal with their chronic rheumatic illnesses,” he said.
This line of research can also help explore the feasibility of telemedicine in helping meet the needs of rural communities facing shortages of rheumatologists.
“Can telemedicine provide a source of rheumatologic access for people who really don’t have a live provider in close proximity?” he said. “I think that’s really why this particular award is very, very timely.”
“It’s so difficult for clinicians to get funding for their research, for their ideas and for the discoveries they were making on a day-to-day basis while they were practicing in a clinical community environment,” he said. “So for me it was really something that inspired me to really create this award.”
A 35-year-old male who takes antiseizure medications, has asymptomatic lesions on his nose and cheeks, present since birth
although up to 75% of cases may be caused by a spontaneous mutation. It is caused by mutations in the TSC1 gene on chromosome 9q34–encoding hamartin or the TSC2 gene on chromosome I6pl3–encoding tuberin. Patients present at birth and males and females are affected equally.
There are multiple skin findings in TS that may herald the diagnosis. The earliest findings are hypopigmented macules, found in 85% of patients. They may be in an ash-leaf shape or confetti pattern. Adenoma sebaceum, or angiofibromas, are present on the forehead, nose, and cheeks, and often present in childhood. Periungual angiofibromas called Koenen tumors tend to occur at puberty. Connective-tissue nevi called Shagreen plaques, or collagenomas, may be present, which is what our patient exhibits on his back. The lumbosacral region is the most common area for these to appear in the first decade of life.
TS can affect other organ systems in the body. Seizures, neuropsychiatric diseases, and mental deficiency are common. Cortical tumors, gliomas, and astrocytomas may develop in the brain. Congenital retinal hamartomas (phakomas) occur. Renal cysts and angiomyolipomas may occur in the kidneys. In the lungs, patients may develop lymphangiomyomatosis. Rhabdomyomas can occur in the heart in infancy and may regress spontaneously over time. Bony changes such as cysts and sclerosis may occur.
Treatment and monitoring of TS requires a multidisciplinary approach with neurology, pulmonology, cardiology, ophthalmology, orthopedics, and dermatology. Cosmetic treatment for angiofibromas includes CO2 laser, shaving, and dermabrasion. Topical rapamycin use has been described in the literature to improve the appearance of angiofibromas. Our patient has been using rapamycin 1% cream for more than 5 years and has had a substantial reduction in the size and number of angiofibromas.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References:
Spitz J. Genodermatoses. A Clinical Guide to Genetic Skin Disorders. Philadelphia: Lippincott Williams & Wilkins, 2005.
James W et al. Andrews’ Diseases of the Skin. Philadelphia: Saunders, 2006.
Bolognia JL et al. Dermatology. London: Mosby Elsevier, 2008.
although up to 75% of cases may be caused by a spontaneous mutation. It is caused by mutations in the TSC1 gene on chromosome 9q34–encoding hamartin or the TSC2 gene on chromosome I6pl3–encoding tuberin. Patients present at birth and males and females are affected equally.
There are multiple skin findings in TS that may herald the diagnosis. The earliest findings are hypopigmented macules, found in 85% of patients. They may be in an ash-leaf shape or confetti pattern. Adenoma sebaceum, or angiofibromas, are present on the forehead, nose, and cheeks, and often present in childhood. Periungual angiofibromas called Koenen tumors tend to occur at puberty. Connective-tissue nevi called Shagreen plaques, or collagenomas, may be present, which is what our patient exhibits on his back. The lumbosacral region is the most common area for these to appear in the first decade of life.
TS can affect other organ systems in the body. Seizures, neuropsychiatric diseases, and mental deficiency are common. Cortical tumors, gliomas, and astrocytomas may develop in the brain. Congenital retinal hamartomas (phakomas) occur. Renal cysts and angiomyolipomas may occur in the kidneys. In the lungs, patients may develop lymphangiomyomatosis. Rhabdomyomas can occur in the heart in infancy and may regress spontaneously over time. Bony changes such as cysts and sclerosis may occur.
Treatment and monitoring of TS requires a multidisciplinary approach with neurology, pulmonology, cardiology, ophthalmology, orthopedics, and dermatology. Cosmetic treatment for angiofibromas includes CO2 laser, shaving, and dermabrasion. Topical rapamycin use has been described in the literature to improve the appearance of angiofibromas. Our patient has been using rapamycin 1% cream for more than 5 years and has had a substantial reduction in the size and number of angiofibromas.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References:
Spitz J. Genodermatoses. A Clinical Guide to Genetic Skin Disorders. Philadelphia: Lippincott Williams & Wilkins, 2005.
James W et al. Andrews’ Diseases of the Skin. Philadelphia: Saunders, 2006.
Bolognia JL et al. Dermatology. London: Mosby Elsevier, 2008.
although up to 75% of cases may be caused by a spontaneous mutation. It is caused by mutations in the TSC1 gene on chromosome 9q34–encoding hamartin or the TSC2 gene on chromosome I6pl3–encoding tuberin. Patients present at birth and males and females are affected equally.
There are multiple skin findings in TS that may herald the diagnosis. The earliest findings are hypopigmented macules, found in 85% of patients. They may be in an ash-leaf shape or confetti pattern. Adenoma sebaceum, or angiofibromas, are present on the forehead, nose, and cheeks, and often present in childhood. Periungual angiofibromas called Koenen tumors tend to occur at puberty. Connective-tissue nevi called Shagreen plaques, or collagenomas, may be present, which is what our patient exhibits on his back. The lumbosacral region is the most common area for these to appear in the first decade of life.
TS can affect other organ systems in the body. Seizures, neuropsychiatric diseases, and mental deficiency are common. Cortical tumors, gliomas, and astrocytomas may develop in the brain. Congenital retinal hamartomas (phakomas) occur. Renal cysts and angiomyolipomas may occur in the kidneys. In the lungs, patients may develop lymphangiomyomatosis. Rhabdomyomas can occur in the heart in infancy and may regress spontaneously over time. Bony changes such as cysts and sclerosis may occur.
Treatment and monitoring of TS requires a multidisciplinary approach with neurology, pulmonology, cardiology, ophthalmology, orthopedics, and dermatology. Cosmetic treatment for angiofibromas includes CO2 laser, shaving, and dermabrasion. Topical rapamycin use has been described in the literature to improve the appearance of angiofibromas. Our patient has been using rapamycin 1% cream for more than 5 years and has had a substantial reduction in the size and number of angiofibromas.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
References:
Spitz J. Genodermatoses. A Clinical Guide to Genetic Skin Disorders. Philadelphia: Lippincott Williams & Wilkins, 2005.
James W et al. Andrews’ Diseases of the Skin. Philadelphia: Saunders, 2006.
Bolognia JL et al. Dermatology. London: Mosby Elsevier, 2008.
Burnout rates in ICU staff fueled by shortages, overtime
Health care professionals working in critical care settings have been overburdened because of the plethora of COVID-19 cases, which has led to symptoms of burnout in both physicians and nurses, findings from a new study show.
“Overburdening ICU professionals during an extended period of time leads to burnout,” said lead study author Niek Kok, MSc, of IQ healthcare, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands. “All ICU professionals are at the risk of this, and in our study, the incidence of physicians experiencing burnout was significantly higher than that of nurses in June 2020.”
This burnout can be explained by conditions caused by the pandemic, he noted, such as the scarcity of staff and resources and having to work with colleagues who were not qualified to work in critical care but who were there out of necessity.
Mr. Kok presented the findings of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
Burnout highest among critical care physicians
The ICU can be a stressful environment for both patients and health care personnel, and burnout is not uncommon among ICU clinicians. However, COVID-19 has amplified the degree of burnout being experienced by clinicians working in this setting. Critical care physicians now top the list of physicians experiencing burnout, at 51%, up from 44% last year, according to the Medscape report ‘Death by 1000 Thousand Cuts’: Physician Burnout and Suicide Report 2021.
The Medscape Nurse Career Satisfaction Report 2020, while not restricted to those working in critical care, also reported higher rates of burnout, compared with the prepandemic period. The percentage of nurses reporting being “very burned out” prior to the pandemic was 4%. Six months into the pandemic, that percentage soared to 18%.
In this study, Mr. Kok and colleagues examined the prevalence and incidence of burnout symptoms and moral distress in health care professionals working in the ICU, both before and during the COVID-19 pandemic.
“When the COVID-19 pandemic surfaced in the Netherlands, the health care professionals in our hospitals were motivated to do everything they could to provide the best care possible,” said Mr. Kok. “Many of the ICU professionals immediately realized that they would have to work longer hours.”
However, the health care professionals that he spoke with did have mixed feelings. Some were afraid of being infected with the virus, while others said that “it was very interesting times for them and that gave them extra motivation to do the work.
“Some physicians [and] the WHO warned that COVID-19 is not going to weathered by a heroic sprint – it is an arduous marathon that is going to go hand in hand with burnout symptoms,” Mr. Kok added. “It will eat away at our qualified ICU staff.”
Before and after data on burnout
It was widely believed that the COVID-19 pandemic would increase burnout symptoms, as had been demonstrated in studies of previous pandemics. However, Mr. Kok emphasized that there are no before and after measurements that transcend cross-sectional designs.
“The claim [has been] that it increases burnout – but there are no assessments of how it progresses in ICU professionals through time,” he said. “So what we really need is a comparison [of] before and after the pandemic.”
It is quite difficult to obtain this type of information because disruptive events like the COVID-19 pandemic cannot be predicted, he said. Thus, it is challenging to get a baseline measurement. But Mr. Kok pointed out that the study has both “before and after” measurements.
“By coincidence really, we had baseline data to measure the impact of the COVID-19 pandemic and had information that was collected before the pandemic,” he said.
In January 2020, a study began looking at the effects of ethics meetings on moral distress in ICU professionals. Data had been collected on moral distress and burnout on ICU professionals in December 2019. The first COVID-19 cases appeared in the Netherlands in February 2020.
A follow-up study was then conducted in May and June 2020, several months into the pandemic.
The longitudinal open cohort study included all ICU personnel who were working in five units within a single university medical center, plus another adult ICU that was based in a separate teaching hospital.
A total of 352 health care professionals responded to a baseline survey in October through December 2019, and then 233 responded to a follow-up survey sent in May and June 2020. The authors measured burnout symptoms and moral distress with the Maslach Burnout Inventory and the Moral Distress Scale, respectively.
Findings
The overall prevalence of burnout symptoms was 23.0% prior to the pandemic, and that jumped to 36.1% at post-peak time. Higher rates of burnout were reported by nurses (38.0%) than physicians (28.6%).
However, the incidence rate of new burnout cases was higher among physicians, compared with nurses (26.7% vs 21.9%). Not surprisingly, a higher prevalence of burnout symptoms was observed in the post-peak period for all clinicians (odds ratio, 1.83; 95% confidence interval, 1.32-2.53), and was higher for nurses (odds ratio, 1.77; 95% confidence interval, 1.03-3.04), for those working overtime (OR, 2.11; 95% CI, 1.48-3.02), and for personnel who directly engaged in patient care (OR, 1.87; 95% CI, 1.35-2.60).
Physicians in general were much more likely to develop burnout symptoms related to the pandemic, compared with nurses (OR, 3.56; 95% CI, 1.06-12.21).
When looking at findings on moral distress, Kok pointed out that it often arises in situations when the health care professional knows the right thing to do but is prevented from doing so. “Morally distressful situations all rose from December to June,” said Mr. Kok. “Scarcity was the most distressing. The other was where colleagues were perceived to be less skilled, and this had to do with the recruitment of people from outside of the ICU to provide care.”
Moral distress from scarcity and unskilled colleagues were both significantly related to burnout, he noted.
In the final model, working in a COVID-19 unit, stress from scarcity of resources and people, stress from unskilled colleagues, and stress from unsafe conditions were all related to burnout. “The stress of physicians was significantly higher,” said Kok. “Even though nurses had higher baseline burnout, it became less pronounced in June 2020. This indicates that burnout was significantly higher in physicians.”
Thus, Mr. Kok and colleagues concluded that overburdening ICU professionals during an extended period of time leads to burnout, and all ICU workers are at risk.
Burnout rates higher in physicians
Weighing in on the study, Greg S. Martin, MD, FCCP, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that the differences observed between physicians and nurses may have to do with the fact that “nurses have been smoldering all along and experiencing higher rates of burnout.
“They may have adapted better to the pandemic conditions, since they are more used to working overtime and short staffed, and spending far more time at the bedside,” he said. “Because of the volume of patients, physicians may be spending more hours doing patient care and are experiencing more burnout.”
For physicians, this may be a more significant change in the workload, as well as the complexity of the situation because of the pandemic. “Many things layer into it, such as [the fact] that there are no families present to give patients support, the complexity of care of these patients, and things like lack of PPE,” Dr. Martin said.
The study did not differentiate among physician groups, so it is unclear if the affected physicians were residents, fellows, or more senior staff. “Residents are often quite busy already, and don’t usually have the capacity to add more to their schedules, and maybe attendings were having to spend more time doing patient care,” Dr. Martin said. “In the United States, at least some personnel were restricted from working with COVID-19 patients. Medical students were removed in many places as well as nonessential staff, so that may have also added to their burnout.”
The study was conducted in the Netherlands, so there may be differences in the work environment, responsibilities of nurses vs. physicians, staffing, and so on. “But it still shows that burnout is very real among doctors and nurses working in the ICU in pandemic conditions,” he said.
Health care professionals working in critical care settings have been overburdened because of the plethora of COVID-19 cases, which has led to symptoms of burnout in both physicians and nurses, findings from a new study show.
“Overburdening ICU professionals during an extended period of time leads to burnout,” said lead study author Niek Kok, MSc, of IQ healthcare, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands. “All ICU professionals are at the risk of this, and in our study, the incidence of physicians experiencing burnout was significantly higher than that of nurses in June 2020.”
This burnout can be explained by conditions caused by the pandemic, he noted, such as the scarcity of staff and resources and having to work with colleagues who were not qualified to work in critical care but who were there out of necessity.
Mr. Kok presented the findings of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
Burnout highest among critical care physicians
The ICU can be a stressful environment for both patients and health care personnel, and burnout is not uncommon among ICU clinicians. However, COVID-19 has amplified the degree of burnout being experienced by clinicians working in this setting. Critical care physicians now top the list of physicians experiencing burnout, at 51%, up from 44% last year, according to the Medscape report ‘Death by 1000 Thousand Cuts’: Physician Burnout and Suicide Report 2021.
The Medscape Nurse Career Satisfaction Report 2020, while not restricted to those working in critical care, also reported higher rates of burnout, compared with the prepandemic period. The percentage of nurses reporting being “very burned out” prior to the pandemic was 4%. Six months into the pandemic, that percentage soared to 18%.
In this study, Mr. Kok and colleagues examined the prevalence and incidence of burnout symptoms and moral distress in health care professionals working in the ICU, both before and during the COVID-19 pandemic.
“When the COVID-19 pandemic surfaced in the Netherlands, the health care professionals in our hospitals were motivated to do everything they could to provide the best care possible,” said Mr. Kok. “Many of the ICU professionals immediately realized that they would have to work longer hours.”
However, the health care professionals that he spoke with did have mixed feelings. Some were afraid of being infected with the virus, while others said that “it was very interesting times for them and that gave them extra motivation to do the work.
“Some physicians [and] the WHO warned that COVID-19 is not going to weathered by a heroic sprint – it is an arduous marathon that is going to go hand in hand with burnout symptoms,” Mr. Kok added. “It will eat away at our qualified ICU staff.”
Before and after data on burnout
It was widely believed that the COVID-19 pandemic would increase burnout symptoms, as had been demonstrated in studies of previous pandemics. However, Mr. Kok emphasized that there are no before and after measurements that transcend cross-sectional designs.
“The claim [has been] that it increases burnout – but there are no assessments of how it progresses in ICU professionals through time,” he said. “So what we really need is a comparison [of] before and after the pandemic.”
It is quite difficult to obtain this type of information because disruptive events like the COVID-19 pandemic cannot be predicted, he said. Thus, it is challenging to get a baseline measurement. But Mr. Kok pointed out that the study has both “before and after” measurements.
“By coincidence really, we had baseline data to measure the impact of the COVID-19 pandemic and had information that was collected before the pandemic,” he said.
In January 2020, a study began looking at the effects of ethics meetings on moral distress in ICU professionals. Data had been collected on moral distress and burnout on ICU professionals in December 2019. The first COVID-19 cases appeared in the Netherlands in February 2020.
A follow-up study was then conducted in May and June 2020, several months into the pandemic.
The longitudinal open cohort study included all ICU personnel who were working in five units within a single university medical center, plus another adult ICU that was based in a separate teaching hospital.
A total of 352 health care professionals responded to a baseline survey in October through December 2019, and then 233 responded to a follow-up survey sent in May and June 2020. The authors measured burnout symptoms and moral distress with the Maslach Burnout Inventory and the Moral Distress Scale, respectively.
Findings
The overall prevalence of burnout symptoms was 23.0% prior to the pandemic, and that jumped to 36.1% at post-peak time. Higher rates of burnout were reported by nurses (38.0%) than physicians (28.6%).
However, the incidence rate of new burnout cases was higher among physicians, compared with nurses (26.7% vs 21.9%). Not surprisingly, a higher prevalence of burnout symptoms was observed in the post-peak period for all clinicians (odds ratio, 1.83; 95% confidence interval, 1.32-2.53), and was higher for nurses (odds ratio, 1.77; 95% confidence interval, 1.03-3.04), for those working overtime (OR, 2.11; 95% CI, 1.48-3.02), and for personnel who directly engaged in patient care (OR, 1.87; 95% CI, 1.35-2.60).
Physicians in general were much more likely to develop burnout symptoms related to the pandemic, compared with nurses (OR, 3.56; 95% CI, 1.06-12.21).
When looking at findings on moral distress, Kok pointed out that it often arises in situations when the health care professional knows the right thing to do but is prevented from doing so. “Morally distressful situations all rose from December to June,” said Mr. Kok. “Scarcity was the most distressing. The other was where colleagues were perceived to be less skilled, and this had to do with the recruitment of people from outside of the ICU to provide care.”
Moral distress from scarcity and unskilled colleagues were both significantly related to burnout, he noted.
In the final model, working in a COVID-19 unit, stress from scarcity of resources and people, stress from unskilled colleagues, and stress from unsafe conditions were all related to burnout. “The stress of physicians was significantly higher,” said Kok. “Even though nurses had higher baseline burnout, it became less pronounced in June 2020. This indicates that burnout was significantly higher in physicians.”
Thus, Mr. Kok and colleagues concluded that overburdening ICU professionals during an extended period of time leads to burnout, and all ICU workers are at risk.
Burnout rates higher in physicians
Weighing in on the study, Greg S. Martin, MD, FCCP, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that the differences observed between physicians and nurses may have to do with the fact that “nurses have been smoldering all along and experiencing higher rates of burnout.
“They may have adapted better to the pandemic conditions, since they are more used to working overtime and short staffed, and spending far more time at the bedside,” he said. “Because of the volume of patients, physicians may be spending more hours doing patient care and are experiencing more burnout.”
For physicians, this may be a more significant change in the workload, as well as the complexity of the situation because of the pandemic. “Many things layer into it, such as [the fact] that there are no families present to give patients support, the complexity of care of these patients, and things like lack of PPE,” Dr. Martin said.
The study did not differentiate among physician groups, so it is unclear if the affected physicians were residents, fellows, or more senior staff. “Residents are often quite busy already, and don’t usually have the capacity to add more to their schedules, and maybe attendings were having to spend more time doing patient care,” Dr. Martin said. “In the United States, at least some personnel were restricted from working with COVID-19 patients. Medical students were removed in many places as well as nonessential staff, so that may have also added to their burnout.”
The study was conducted in the Netherlands, so there may be differences in the work environment, responsibilities of nurses vs. physicians, staffing, and so on. “But it still shows that burnout is very real among doctors and nurses working in the ICU in pandemic conditions,” he said.
Health care professionals working in critical care settings have been overburdened because of the plethora of COVID-19 cases, which has led to symptoms of burnout in both physicians and nurses, findings from a new study show.
“Overburdening ICU professionals during an extended period of time leads to burnout,” said lead study author Niek Kok, MSc, of IQ healthcare, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands. “All ICU professionals are at the risk of this, and in our study, the incidence of physicians experiencing burnout was significantly higher than that of nurses in June 2020.”
This burnout can be explained by conditions caused by the pandemic, he noted, such as the scarcity of staff and resources and having to work with colleagues who were not qualified to work in critical care but who were there out of necessity.
Mr. Kok presented the findings of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
Burnout highest among critical care physicians
The ICU can be a stressful environment for both patients and health care personnel, and burnout is not uncommon among ICU clinicians. However, COVID-19 has amplified the degree of burnout being experienced by clinicians working in this setting. Critical care physicians now top the list of physicians experiencing burnout, at 51%, up from 44% last year, according to the Medscape report ‘Death by 1000 Thousand Cuts’: Physician Burnout and Suicide Report 2021.
The Medscape Nurse Career Satisfaction Report 2020, while not restricted to those working in critical care, also reported higher rates of burnout, compared with the prepandemic period. The percentage of nurses reporting being “very burned out” prior to the pandemic was 4%. Six months into the pandemic, that percentage soared to 18%.
In this study, Mr. Kok and colleagues examined the prevalence and incidence of burnout symptoms and moral distress in health care professionals working in the ICU, both before and during the COVID-19 pandemic.
“When the COVID-19 pandemic surfaced in the Netherlands, the health care professionals in our hospitals were motivated to do everything they could to provide the best care possible,” said Mr. Kok. “Many of the ICU professionals immediately realized that they would have to work longer hours.”
However, the health care professionals that he spoke with did have mixed feelings. Some were afraid of being infected with the virus, while others said that “it was very interesting times for them and that gave them extra motivation to do the work.
“Some physicians [and] the WHO warned that COVID-19 is not going to weathered by a heroic sprint – it is an arduous marathon that is going to go hand in hand with burnout symptoms,” Mr. Kok added. “It will eat away at our qualified ICU staff.”
Before and after data on burnout
It was widely believed that the COVID-19 pandemic would increase burnout symptoms, as had been demonstrated in studies of previous pandemics. However, Mr. Kok emphasized that there are no before and after measurements that transcend cross-sectional designs.
“The claim [has been] that it increases burnout – but there are no assessments of how it progresses in ICU professionals through time,” he said. “So what we really need is a comparison [of] before and after the pandemic.”
It is quite difficult to obtain this type of information because disruptive events like the COVID-19 pandemic cannot be predicted, he said. Thus, it is challenging to get a baseline measurement. But Mr. Kok pointed out that the study has both “before and after” measurements.
“By coincidence really, we had baseline data to measure the impact of the COVID-19 pandemic and had information that was collected before the pandemic,” he said.
In January 2020, a study began looking at the effects of ethics meetings on moral distress in ICU professionals. Data had been collected on moral distress and burnout on ICU professionals in December 2019. The first COVID-19 cases appeared in the Netherlands in February 2020.
A follow-up study was then conducted in May and June 2020, several months into the pandemic.
The longitudinal open cohort study included all ICU personnel who were working in five units within a single university medical center, plus another adult ICU that was based in a separate teaching hospital.
A total of 352 health care professionals responded to a baseline survey in October through December 2019, and then 233 responded to a follow-up survey sent in May and June 2020. The authors measured burnout symptoms and moral distress with the Maslach Burnout Inventory and the Moral Distress Scale, respectively.
Findings
The overall prevalence of burnout symptoms was 23.0% prior to the pandemic, and that jumped to 36.1% at post-peak time. Higher rates of burnout were reported by nurses (38.0%) than physicians (28.6%).
However, the incidence rate of new burnout cases was higher among physicians, compared with nurses (26.7% vs 21.9%). Not surprisingly, a higher prevalence of burnout symptoms was observed in the post-peak period for all clinicians (odds ratio, 1.83; 95% confidence interval, 1.32-2.53), and was higher for nurses (odds ratio, 1.77; 95% confidence interval, 1.03-3.04), for those working overtime (OR, 2.11; 95% CI, 1.48-3.02), and for personnel who directly engaged in patient care (OR, 1.87; 95% CI, 1.35-2.60).
Physicians in general were much more likely to develop burnout symptoms related to the pandemic, compared with nurses (OR, 3.56; 95% CI, 1.06-12.21).
When looking at findings on moral distress, Kok pointed out that it often arises in situations when the health care professional knows the right thing to do but is prevented from doing so. “Morally distressful situations all rose from December to June,” said Mr. Kok. “Scarcity was the most distressing. The other was where colleagues were perceived to be less skilled, and this had to do with the recruitment of people from outside of the ICU to provide care.”
Moral distress from scarcity and unskilled colleagues were both significantly related to burnout, he noted.
In the final model, working in a COVID-19 unit, stress from scarcity of resources and people, stress from unskilled colleagues, and stress from unsafe conditions were all related to burnout. “The stress of physicians was significantly higher,” said Kok. “Even though nurses had higher baseline burnout, it became less pronounced in June 2020. This indicates that burnout was significantly higher in physicians.”
Thus, Mr. Kok and colleagues concluded that overburdening ICU professionals during an extended period of time leads to burnout, and all ICU workers are at risk.
Burnout rates higher in physicians
Weighing in on the study, Greg S. Martin, MD, FCCP, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that the differences observed between physicians and nurses may have to do with the fact that “nurses have been smoldering all along and experiencing higher rates of burnout.
“They may have adapted better to the pandemic conditions, since they are more used to working overtime and short staffed, and spending far more time at the bedside,” he said. “Because of the volume of patients, physicians may be spending more hours doing patient care and are experiencing more burnout.”
For physicians, this may be a more significant change in the workload, as well as the complexity of the situation because of the pandemic. “Many things layer into it, such as [the fact] that there are no families present to give patients support, the complexity of care of these patients, and things like lack of PPE,” Dr. Martin said.
The study did not differentiate among physician groups, so it is unclear if the affected physicians were residents, fellows, or more senior staff. “Residents are often quite busy already, and don’t usually have the capacity to add more to their schedules, and maybe attendings were having to spend more time doing patient care,” Dr. Martin said. “In the United States, at least some personnel were restricted from working with COVID-19 patients. Medical students were removed in many places as well as nonessential staff, so that may have also added to their burnout.”
The study was conducted in the Netherlands, so there may be differences in the work environment, responsibilities of nurses vs. physicians, staffing, and so on. “But it still shows that burnout is very real among doctors and nurses working in the ICU in pandemic conditions,” he said.
FROM CCC50
Psychiatrist recounts haunting ordeal with an anonymous stalker
Looking back on his experience of being stalked by a former patient for nearly 1 year, William J. Newman, MD, regrets not reaching out to colleagues about the patient boundary violations earlier than he did.
“My mindset was: ‘Maybe I did something wrong that created this,’ ” Dr. Newman, professor and interim chair of psychiatry at Saint Louis University, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “That’s a common theme among victims of stalking, being kind of embarrassed and not wanting to share it with other people.”
Dr. Newman’s ordeal began in August 2014, when the first of several threatening emails messages were sent to his account at the University of California, Davis, where he held a faculty post and worked on the teaching service at the Sacramento Mental Health Treatment Center, a county hospital that serves mainly uninsured or underinsured populations. The messages always contained a nonspecific email recipient name and the first wasn’t terribly worrisome, Dr. Newman said. It basically read (profanities excluded): “What is wrong with you? Leave me alone. All I want is some privacy.”
About 3 months later, he received another message in a similar writing pattern, but the name of the sender was “god devil,” which raised a red flag to him. “Once you start to get religious concepts, people are compelled to commit acts when they believe they’re doing so beyond the laws of the land and are doing so for a religious purpose,” said Dr. Newman, who is immediate past president of the American Academy of Psychiatry and the Law.
The content of the message contained the first name of a coworker and phrasing inferring suicide, which gave Dr. Newman a hint that it was someone he had cared for at the mental health treatment center, “but as anybody who has worked on a busy inpatient service can tell you, you encounter several suicidal patients, and this didn’t really narrow it down,” he said. “This told me the person had presented after a suicide attempt. In some ways, that made me a little more concerned, because because they don’t really worry about the consequences of being shot by law enforcement or dying in an attack.”
Dr. Newman contacted the university’s information technology team, which was able to trace all messages to an IP address from a computer located at a downtown branch of the public library, which had surveillance video. Armed with this information, he contacted the Sacramento Police Department to see if they would help. He had “what I can only describe as an unsatisfying and somewhat condescending conversation with an officer, who said: ‘Sir, we can’t just go around asking people questions without knowing they did something wrong. There’s nothing we’re going to do.’ ”
Between November 2014 and May 2015, Dr. Newman continued to receive periodic messages from the individual of varied length and intensity.
“Some messages were more disorganized and difficult to follow, while others were very intense and pointed about my imminent death,” he recalled. “I started to ignore these messages as much as possible, tried to put my head in the sand and move forward.”
However, one phrase contained in a message read “you won’t even recognize me,” which gave Dr. Newman pause. “It highlighted the idea that because I don’t know who this is, they could walk up to me on the sidewalk, and I would have no idea, which in its own right is somewhat terrorizing.”
At this point, he contacted the police again, telling them he was fearful for his imminent safety. He also met with his department chair and administrators, who helped Dr. Newman develop a plan to enter and exit the hospital at different times. Then, in May 2015, the stalker sent Dr. Newman another email message threatening not only his life, but the lives of his colleagues at the hospital.
“This was viewed as a terroristic threat, because [it inferred that] other people were going to be shot other than just me,” he said.
After this, Dr. Newman’s administrators contacted the police about the threat, who identified the individual through video surveillance footage at the public library and began to search for him. It was a patient who had been on testosterone and previously had sent similar messages to another mental health provider in town and wound up showing up at that person’s office with a loaded firearm.
“At that point, the police were called to the scene, picked the individual up, and took him to a local emergency room where he was placed on an involuntary 5150 psychiatric hold,” he said. “It was frustrating to me that this was very much minimized and kind of put to the side.”
Once he learned the stalker’s name, Dr. Newman had no recollection of the individual. “The patient had presented after a carbon monoxide overdose, had been sent to a local emergency room and came to my service,” he said. “It was a very nonconfrontational hospitalization, nothing out of the ordinary.”
At this point, the stalker was still at large, so Dr. Newman wrote farewell notes to his wife, children, and loved ones, “just in case,” he said. “I had those tucked away. That wasn’t an overly pleasant experience.” He also lived away from his family outside of Sacramento while police searched for his stalker.
In late May 2015, police located and arrested the individual, and Dr. Newman began a series of conversations with the District Attorney’s office. “They told me there were seven terroristic threat charges that had been levied. They said they were taking this very seriously and [that the case] would be going to trial.” About 1 year later, after Dr. Newman’s move to Missouri, the District Attorney indicated that there would be a court trial and that Dr. Newman would be asked to serve as a fact witness. “I gave them all the information I had, talked to investigators, and the process was moving along for about a year to the point that they had an anticipated trial date,” he said. About 1 year later, he received an automated phone message which stated that the individual had been released from jail. He called the District Attorney to ask what happened.
“He said the judge didn’t really want to deal with this [case] anymore, and accepted a plea with time served and released him,” Dr. Newman said. “That was the outcome of the situation.”
According to a 1997 study of 100 stalking victims, 94% made major lifestyle changes after their ordeal, 82% modified usual activities, 73% increased security measures, 70% curtailed social outings, 53% decreased/stopped work or school, and 39% relocated. “You do change a lot of what you do and how you do it in your life when you’ve had this experience, especially when it’s been a chronic experience for months or years,” said Dr. Newman, who is also medical director of adult psychiatric inpatient services for Saint Louis University. “To this day I get antsy any time I think about the story or prepare to talk about it. It remains uncomfortable even 6 years later, even without an ongoing direct threat at this point.”
The physiological impact of chronic stalking also takes its toll. The body releases adrenaline and cortisol as part of the fight or flight response, while chronic stress “is when you feel an increased stress response and have adrenaline and cortisol elevated for an extended period of time,” he said. “There are negative impacts in terms of increased inflammation in the body and in the brain. I have spoken to several professionals who have been stalked by former patients. Commonly, they have been diagnosed in the period after that with an autoimmune illness or a cancer. Less than a year after my stalking situation ended, I was diagnosed with a metastatic cancer and had to start chemotherapy. I would not at all be surprised that those things are highly related to one another.”
When patient boundary violations start to become problematic or worrisome, Dr. Newman advised reaching out to colleagues and law enforcement for help. “Don’t let it go on insidiously for an extended period of time,” he said. “I think that was the biggest lesson I learned.”
He reported having no financial disclosures.
Looking back on his experience of being stalked by a former patient for nearly 1 year, William J. Newman, MD, regrets not reaching out to colleagues about the patient boundary violations earlier than he did.
“My mindset was: ‘Maybe I did something wrong that created this,’ ” Dr. Newman, professor and interim chair of psychiatry at Saint Louis University, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “That’s a common theme among victims of stalking, being kind of embarrassed and not wanting to share it with other people.”
Dr. Newman’s ordeal began in August 2014, when the first of several threatening emails messages were sent to his account at the University of California, Davis, where he held a faculty post and worked on the teaching service at the Sacramento Mental Health Treatment Center, a county hospital that serves mainly uninsured or underinsured populations. The messages always contained a nonspecific email recipient name and the first wasn’t terribly worrisome, Dr. Newman said. It basically read (profanities excluded): “What is wrong with you? Leave me alone. All I want is some privacy.”
About 3 months later, he received another message in a similar writing pattern, but the name of the sender was “god devil,” which raised a red flag to him. “Once you start to get religious concepts, people are compelled to commit acts when they believe they’re doing so beyond the laws of the land and are doing so for a religious purpose,” said Dr. Newman, who is immediate past president of the American Academy of Psychiatry and the Law.
The content of the message contained the first name of a coworker and phrasing inferring suicide, which gave Dr. Newman a hint that it was someone he had cared for at the mental health treatment center, “but as anybody who has worked on a busy inpatient service can tell you, you encounter several suicidal patients, and this didn’t really narrow it down,” he said. “This told me the person had presented after a suicide attempt. In some ways, that made me a little more concerned, because because they don’t really worry about the consequences of being shot by law enforcement or dying in an attack.”
Dr. Newman contacted the university’s information technology team, which was able to trace all messages to an IP address from a computer located at a downtown branch of the public library, which had surveillance video. Armed with this information, he contacted the Sacramento Police Department to see if they would help. He had “what I can only describe as an unsatisfying and somewhat condescending conversation with an officer, who said: ‘Sir, we can’t just go around asking people questions without knowing they did something wrong. There’s nothing we’re going to do.’ ”
Between November 2014 and May 2015, Dr. Newman continued to receive periodic messages from the individual of varied length and intensity.
“Some messages were more disorganized and difficult to follow, while others were very intense and pointed about my imminent death,” he recalled. “I started to ignore these messages as much as possible, tried to put my head in the sand and move forward.”
However, one phrase contained in a message read “you won’t even recognize me,” which gave Dr. Newman pause. “It highlighted the idea that because I don’t know who this is, they could walk up to me on the sidewalk, and I would have no idea, which in its own right is somewhat terrorizing.”
At this point, he contacted the police again, telling them he was fearful for his imminent safety. He also met with his department chair and administrators, who helped Dr. Newman develop a plan to enter and exit the hospital at different times. Then, in May 2015, the stalker sent Dr. Newman another email message threatening not only his life, but the lives of his colleagues at the hospital.
“This was viewed as a terroristic threat, because [it inferred that] other people were going to be shot other than just me,” he said.
After this, Dr. Newman’s administrators contacted the police about the threat, who identified the individual through video surveillance footage at the public library and began to search for him. It was a patient who had been on testosterone and previously had sent similar messages to another mental health provider in town and wound up showing up at that person’s office with a loaded firearm.
“At that point, the police were called to the scene, picked the individual up, and took him to a local emergency room where he was placed on an involuntary 5150 psychiatric hold,” he said. “It was frustrating to me that this was very much minimized and kind of put to the side.”
Once he learned the stalker’s name, Dr. Newman had no recollection of the individual. “The patient had presented after a carbon monoxide overdose, had been sent to a local emergency room and came to my service,” he said. “It was a very nonconfrontational hospitalization, nothing out of the ordinary.”
At this point, the stalker was still at large, so Dr. Newman wrote farewell notes to his wife, children, and loved ones, “just in case,” he said. “I had those tucked away. That wasn’t an overly pleasant experience.” He also lived away from his family outside of Sacramento while police searched for his stalker.
In late May 2015, police located and arrested the individual, and Dr. Newman began a series of conversations with the District Attorney’s office. “They told me there were seven terroristic threat charges that had been levied. They said they were taking this very seriously and [that the case] would be going to trial.” About 1 year later, after Dr. Newman’s move to Missouri, the District Attorney indicated that there would be a court trial and that Dr. Newman would be asked to serve as a fact witness. “I gave them all the information I had, talked to investigators, and the process was moving along for about a year to the point that they had an anticipated trial date,” he said. About 1 year later, he received an automated phone message which stated that the individual had been released from jail. He called the District Attorney to ask what happened.
“He said the judge didn’t really want to deal with this [case] anymore, and accepted a plea with time served and released him,” Dr. Newman said. “That was the outcome of the situation.”
According to a 1997 study of 100 stalking victims, 94% made major lifestyle changes after their ordeal, 82% modified usual activities, 73% increased security measures, 70% curtailed social outings, 53% decreased/stopped work or school, and 39% relocated. “You do change a lot of what you do and how you do it in your life when you’ve had this experience, especially when it’s been a chronic experience for months or years,” said Dr. Newman, who is also medical director of adult psychiatric inpatient services for Saint Louis University. “To this day I get antsy any time I think about the story or prepare to talk about it. It remains uncomfortable even 6 years later, even without an ongoing direct threat at this point.”
The physiological impact of chronic stalking also takes its toll. The body releases adrenaline and cortisol as part of the fight or flight response, while chronic stress “is when you feel an increased stress response and have adrenaline and cortisol elevated for an extended period of time,” he said. “There are negative impacts in terms of increased inflammation in the body and in the brain. I have spoken to several professionals who have been stalked by former patients. Commonly, they have been diagnosed in the period after that with an autoimmune illness or a cancer. Less than a year after my stalking situation ended, I was diagnosed with a metastatic cancer and had to start chemotherapy. I would not at all be surprised that those things are highly related to one another.”
When patient boundary violations start to become problematic or worrisome, Dr. Newman advised reaching out to colleagues and law enforcement for help. “Don’t let it go on insidiously for an extended period of time,” he said. “I think that was the biggest lesson I learned.”
He reported having no financial disclosures.
Looking back on his experience of being stalked by a former patient for nearly 1 year, William J. Newman, MD, regrets not reaching out to colleagues about the patient boundary violations earlier than he did.
“My mindset was: ‘Maybe I did something wrong that created this,’ ” Dr. Newman, professor and interim chair of psychiatry at Saint Louis University, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “That’s a common theme among victims of stalking, being kind of embarrassed and not wanting to share it with other people.”
Dr. Newman’s ordeal began in August 2014, when the first of several threatening emails messages were sent to his account at the University of California, Davis, where he held a faculty post and worked on the teaching service at the Sacramento Mental Health Treatment Center, a county hospital that serves mainly uninsured or underinsured populations. The messages always contained a nonspecific email recipient name and the first wasn’t terribly worrisome, Dr. Newman said. It basically read (profanities excluded): “What is wrong with you? Leave me alone. All I want is some privacy.”
About 3 months later, he received another message in a similar writing pattern, but the name of the sender was “god devil,” which raised a red flag to him. “Once you start to get religious concepts, people are compelled to commit acts when they believe they’re doing so beyond the laws of the land and are doing so for a religious purpose,” said Dr. Newman, who is immediate past president of the American Academy of Psychiatry and the Law.
The content of the message contained the first name of a coworker and phrasing inferring suicide, which gave Dr. Newman a hint that it was someone he had cared for at the mental health treatment center, “but as anybody who has worked on a busy inpatient service can tell you, you encounter several suicidal patients, and this didn’t really narrow it down,” he said. “This told me the person had presented after a suicide attempt. In some ways, that made me a little more concerned, because because they don’t really worry about the consequences of being shot by law enforcement or dying in an attack.”
Dr. Newman contacted the university’s information technology team, which was able to trace all messages to an IP address from a computer located at a downtown branch of the public library, which had surveillance video. Armed with this information, he contacted the Sacramento Police Department to see if they would help. He had “what I can only describe as an unsatisfying and somewhat condescending conversation with an officer, who said: ‘Sir, we can’t just go around asking people questions without knowing they did something wrong. There’s nothing we’re going to do.’ ”
Between November 2014 and May 2015, Dr. Newman continued to receive periodic messages from the individual of varied length and intensity.
“Some messages were more disorganized and difficult to follow, while others were very intense and pointed about my imminent death,” he recalled. “I started to ignore these messages as much as possible, tried to put my head in the sand and move forward.”
However, one phrase contained in a message read “you won’t even recognize me,” which gave Dr. Newman pause. “It highlighted the idea that because I don’t know who this is, they could walk up to me on the sidewalk, and I would have no idea, which in its own right is somewhat terrorizing.”
At this point, he contacted the police again, telling them he was fearful for his imminent safety. He also met with his department chair and administrators, who helped Dr. Newman develop a plan to enter and exit the hospital at different times. Then, in May 2015, the stalker sent Dr. Newman another email message threatening not only his life, but the lives of his colleagues at the hospital.
“This was viewed as a terroristic threat, because [it inferred that] other people were going to be shot other than just me,” he said.
After this, Dr. Newman’s administrators contacted the police about the threat, who identified the individual through video surveillance footage at the public library and began to search for him. It was a patient who had been on testosterone and previously had sent similar messages to another mental health provider in town and wound up showing up at that person’s office with a loaded firearm.
“At that point, the police were called to the scene, picked the individual up, and took him to a local emergency room where he was placed on an involuntary 5150 psychiatric hold,” he said. “It was frustrating to me that this was very much minimized and kind of put to the side.”
Once he learned the stalker’s name, Dr. Newman had no recollection of the individual. “The patient had presented after a carbon monoxide overdose, had been sent to a local emergency room and came to my service,” he said. “It was a very nonconfrontational hospitalization, nothing out of the ordinary.”
At this point, the stalker was still at large, so Dr. Newman wrote farewell notes to his wife, children, and loved ones, “just in case,” he said. “I had those tucked away. That wasn’t an overly pleasant experience.” He also lived away from his family outside of Sacramento while police searched for his stalker.
In late May 2015, police located and arrested the individual, and Dr. Newman began a series of conversations with the District Attorney’s office. “They told me there were seven terroristic threat charges that had been levied. They said they were taking this very seriously and [that the case] would be going to trial.” About 1 year later, after Dr. Newman’s move to Missouri, the District Attorney indicated that there would be a court trial and that Dr. Newman would be asked to serve as a fact witness. “I gave them all the information I had, talked to investigators, and the process was moving along for about a year to the point that they had an anticipated trial date,” he said. About 1 year later, he received an automated phone message which stated that the individual had been released from jail. He called the District Attorney to ask what happened.
“He said the judge didn’t really want to deal with this [case] anymore, and accepted a plea with time served and released him,” Dr. Newman said. “That was the outcome of the situation.”
According to a 1997 study of 100 stalking victims, 94% made major lifestyle changes after their ordeal, 82% modified usual activities, 73% increased security measures, 70% curtailed social outings, 53% decreased/stopped work or school, and 39% relocated. “You do change a lot of what you do and how you do it in your life when you’ve had this experience, especially when it’s been a chronic experience for months or years,” said Dr. Newman, who is also medical director of adult psychiatric inpatient services for Saint Louis University. “To this day I get antsy any time I think about the story or prepare to talk about it. It remains uncomfortable even 6 years later, even without an ongoing direct threat at this point.”
The physiological impact of chronic stalking also takes its toll. The body releases adrenaline and cortisol as part of the fight or flight response, while chronic stress “is when you feel an increased stress response and have adrenaline and cortisol elevated for an extended period of time,” he said. “There are negative impacts in terms of increased inflammation in the body and in the brain. I have spoken to several professionals who have been stalked by former patients. Commonly, they have been diagnosed in the period after that with an autoimmune illness or a cancer. Less than a year after my stalking situation ended, I was diagnosed with a metastatic cancer and had to start chemotherapy. I would not at all be surprised that those things are highly related to one another.”
When patient boundary violations start to become problematic or worrisome, Dr. Newman advised reaching out to colleagues and law enforcement for help. “Don’t let it go on insidiously for an extended period of time,” he said. “I think that was the biggest lesson I learned.”
He reported having no financial disclosures.
FROM NPA 2021
ColCORONA: More questions than answers for colchicine in COVID-19
Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.
As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.
But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.
Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”
When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).
Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.
“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.
“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.
“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”
The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.
Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).
The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.
“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”
Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”
Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.
“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.
“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”
According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.
Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.
Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”
The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.
The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”
Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”
The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.
The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.
Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”
Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”
He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.
“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”
Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.
Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.
“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.
The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
A version of this article first appeared on Medscape.com.
Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.
As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.
But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.
Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”
When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).
Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.
“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.
“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.
“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”
The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.
Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).
The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.
“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”
Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”
Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.
“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.
“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”
According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.
Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.
Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”
The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.
The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”
Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”
The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.
The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.
Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”
Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”
He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.
“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”
Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.
Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.
“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.
The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
A version of this article first appeared on Medscape.com.
Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.
As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.
But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.
Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”
When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).
Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.
“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.
“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.
“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”
The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.
Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).
The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.
“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”
Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”
Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.
“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.
“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”
According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.
Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.
Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”
The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.
The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”
Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”
The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.
The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.
Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”
Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”
He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.
“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”
Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.
Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.
“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.
The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
A version of this article first appeared on Medscape.com.
Finding a new approach to difficult diagnoses
Reducing – or managing – uncertainty
Beyond its clinical objective, the Socrates Project also seeks to further the discovery of previously unrecognized disease processes.
Many patients do not have a diagnosis that explains their signs and symptoms, despite a thorough evaluation, said Benjamin Singer, MD, assistant professor of pulmonology and critical care at Northwestern Medicine in Chicago. To address that problem, he and his colleagues launched the Socrates Project. The service is intended for difficult diagnoses and is based on Socratic principles, particularly the role of iterative hypothesis testing in the process of diagnosis.
“We began the Socrates Project to assist physicians caring for patients who lack a specific diagnosis. In creating this service, we have found ourselves to be doctors for doctors – formalizing the curbside consultation,” Dr. Singer said.
Northwestern Medicine launched the Socrates Project in 2015. It’s a physician-to-physician consultation service that assists doctors working to diagnose conditions that have so far eluded detection. “Our service’s goal is to improve patient care by providing an opinion to the referring physician on diagnostic possibilities for a particular case and ideas to reduce – or at least manage – diagnostic uncertainty,” they write. “Our service model is similar to a tumor board, which exists as an interdisciplinary group operating in parallel to the clinical services, to provide consensus-based recommendations.”
Hospitalists at other institutions may be interested in starting a similar type of service at their own institution or collaborating with institutions who offer this type of service, Dr. Singer said.
At Northwestern Medicine, they are at work on the project’s next steps. “We are working to generate systematic data about our practice, particularly the types of referrals and outcomes,” he said.
Reference
1. Singer BD, et al. The Socrates Project for Difficult Diagnosis at Northwestern Medicine. J Hosp Med. 2020 February;15(2):116-125. doi:10.12788/jhm.3335.
Reducing – or managing – uncertainty
Reducing – or managing – uncertainty
Beyond its clinical objective, the Socrates Project also seeks to further the discovery of previously unrecognized disease processes.
Many patients do not have a diagnosis that explains their signs and symptoms, despite a thorough evaluation, said Benjamin Singer, MD, assistant professor of pulmonology and critical care at Northwestern Medicine in Chicago. To address that problem, he and his colleagues launched the Socrates Project. The service is intended for difficult diagnoses and is based on Socratic principles, particularly the role of iterative hypothesis testing in the process of diagnosis.
“We began the Socrates Project to assist physicians caring for patients who lack a specific diagnosis. In creating this service, we have found ourselves to be doctors for doctors – formalizing the curbside consultation,” Dr. Singer said.
Northwestern Medicine launched the Socrates Project in 2015. It’s a physician-to-physician consultation service that assists doctors working to diagnose conditions that have so far eluded detection. “Our service’s goal is to improve patient care by providing an opinion to the referring physician on diagnostic possibilities for a particular case and ideas to reduce – or at least manage – diagnostic uncertainty,” they write. “Our service model is similar to a tumor board, which exists as an interdisciplinary group operating in parallel to the clinical services, to provide consensus-based recommendations.”
Hospitalists at other institutions may be interested in starting a similar type of service at their own institution or collaborating with institutions who offer this type of service, Dr. Singer said.
At Northwestern Medicine, they are at work on the project’s next steps. “We are working to generate systematic data about our practice, particularly the types of referrals and outcomes,” he said.
Reference
1. Singer BD, et al. The Socrates Project for Difficult Diagnosis at Northwestern Medicine. J Hosp Med. 2020 February;15(2):116-125. doi:10.12788/jhm.3335.
Beyond its clinical objective, the Socrates Project also seeks to further the discovery of previously unrecognized disease processes.
Many patients do not have a diagnosis that explains their signs and symptoms, despite a thorough evaluation, said Benjamin Singer, MD, assistant professor of pulmonology and critical care at Northwestern Medicine in Chicago. To address that problem, he and his colleagues launched the Socrates Project. The service is intended for difficult diagnoses and is based on Socratic principles, particularly the role of iterative hypothesis testing in the process of diagnosis.
“We began the Socrates Project to assist physicians caring for patients who lack a specific diagnosis. In creating this service, we have found ourselves to be doctors for doctors – formalizing the curbside consultation,” Dr. Singer said.
Northwestern Medicine launched the Socrates Project in 2015. It’s a physician-to-physician consultation service that assists doctors working to diagnose conditions that have so far eluded detection. “Our service’s goal is to improve patient care by providing an opinion to the referring physician on diagnostic possibilities for a particular case and ideas to reduce – or at least manage – diagnostic uncertainty,” they write. “Our service model is similar to a tumor board, which exists as an interdisciplinary group operating in parallel to the clinical services, to provide consensus-based recommendations.”
Hospitalists at other institutions may be interested in starting a similar type of service at their own institution or collaborating with institutions who offer this type of service, Dr. Singer said.
At Northwestern Medicine, they are at work on the project’s next steps. “We are working to generate systematic data about our practice, particularly the types of referrals and outcomes,” he said.
Reference
1. Singer BD, et al. The Socrates Project for Difficult Diagnosis at Northwestern Medicine. J Hosp Med. 2020 February;15(2):116-125. doi:10.12788/jhm.3335.