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Easing access to DLBCL treatments: Patient study reveals racial differences
, but other “multifaceted and personalized” strategies are also needed, a new study shows.
The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
Treatment decision factors
They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.
When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.
Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.
However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).
Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.
“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.
Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
Why the findings matter
“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.
“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.
“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”
Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.
He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.
These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.
“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
Personalized treatment strategies
The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.
The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.
For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.
Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.
“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”
Next steps
Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.
“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.
Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.
, but other “multifaceted and personalized” strategies are also needed, a new study shows.
The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
Treatment decision factors
They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.
When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.
Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.
However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).
Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.
“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.
Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
Why the findings matter
“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.
“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.
“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”
Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.
He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.
These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.
“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
Personalized treatment strategies
The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.
The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.
For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.
Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.
“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”
Next steps
Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.
“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.
Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.
, but other “multifaceted and personalized” strategies are also needed, a new study shows.
The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
Treatment decision factors
They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.
When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.
Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.
However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).
Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.
“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.
Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
Why the findings matter
“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.
“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.
“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”
Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.
He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.
These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.
“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
Personalized treatment strategies
The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.
The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.
For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.
Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.
“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”
Next steps
Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.
“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.
Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.
FROM JCO
One-quarter of lung cancer patients alive at 5 years
In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.
This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.
“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.
“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”
“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
Lung cancer decreasing but still being diagnosed late
The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.
Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.
However, in almost half of the cases, the disease is diagnosed in late stages.
When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.
At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.
The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).
However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.
“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.
Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.
In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.
Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.
“So we have to change that in the minds of primary care providers as well,” she underscored.
Report highlights racial disparities
The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.
For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.
The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.
First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.
So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.
Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.
“Again, this is something that many doctors are not aware of,” she emphasized.
Dr. McKee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.
This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.
“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.
“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”
“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
Lung cancer decreasing but still being diagnosed late
The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.
Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.
However, in almost half of the cases, the disease is diagnosed in late stages.
When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.
At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.
The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).
However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.
“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.
Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.
In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.
Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.
“So we have to change that in the minds of primary care providers as well,” she underscored.
Report highlights racial disparities
The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.
For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.
The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.
First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.
So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.
Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.
“Again, this is something that many doctors are not aware of,” she emphasized.
Dr. McKee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.
This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.
“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.
“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”
“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
Lung cancer decreasing but still being diagnosed late
The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.
Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.
However, in almost half of the cases, the disease is diagnosed in late stages.
When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.
At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.
The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).
However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.
“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.
Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.
In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.
Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.
“So we have to change that in the minds of primary care providers as well,” she underscored.
Report highlights racial disparities
The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.
For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.
The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.
First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.
So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.
Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.
“Again, this is something that many doctors are not aware of,” she emphasized.
Dr. McKee has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHEST in the news
Creating a stronger voice for CHEST members in pulmonary, critical care, and sleep medicine, CHEST works to provide opportunities for members to serve as expert sources for both mainstream and trade media.
Below are a few highlights of media coverage from the past few months that work to expand awareness of CHEST and to promote the expertise of CHEST members in the media.
The New York Times covers the Philips recall
In August, a New York Times article published quoting incoming CHEST President, David Schulman, MD, MPH, FCCP. The article covered the recent Philips recall and its impact on the COVID-19 pandemic.
Dr. Schulman is quoted saying, “Because the number of people coming into the hospital with severe respiratory symptoms has increased as a result of COVID-19, the demand for these devices has also increased, which is problematic since available supply has decreased as a result of the Philips recall.”
The full article, Breathing Machine Recall Over Possible Cancer Risk Leaves Millions Scrambling for Substitutes, can be found on the New York Times website.
Technical expert panel on coverage determinations
Peter Gay, MD, FCCP, was quoted in an article by McKnight’s Long-Term Care News on the recent technical expert panel recommendations for national coverage determinations for optimal noninvasive ventilation.
“Centers for Medicare & Medicaid Services was wanting rigorous scientific support necessary to clarify the ‘reasonable and necessary’ role of these new mechanical therapeutic modalities where there was none in order to move forward,” said Dr. Gay. “What we have done is create a pathway to simplify the maze of regulation and perhaps most importantly, remove the obstacles that currently exist.”
The full article, Panel on Non-Invasive Ventilation Seeks to Simplify ‘Maze’ of Regulation for Device Coverage, can be found on the McKnight’s Long-Term Care News website.
Asthma and HRT
Originally appearing in HealthDay, U.S. News and World Report covered a recent journal CHEST® publication Hormone Replacement Therapy and Development of New Asthma by Erik Soeren Halvard Hansen, MD, et al.
The study included about 34,500 women who were diagnosed with asthma between 1995 and 2018, when they were 40 to 65 years of age. Each was then compared with 10 asthma-free women.
Based on that comparison, HRT use was associated with a 63% higher risk for developing asthma, according to the study.
The full article, HRT Could Raise Odds for Asthma, can be found on the U.S. News & World Report website.
Pediatric ICU admission and COVID-19
Healio Pulmonology covered a recent journal CHEST publication, Changes in Pediatric ICU Utilization and Clinical Trends During the Coronavirus Pandemic, by Janine E. Zee-Cheng, MD, et al.
“Severe infections, traumatic injuries, perioperative conditions and acute exacerbations of chronic illnesses such as asthma and diabetes are among the most common causes of admission to a pediatric ICU; thus, the epidemiology of pediatric critical illness was likely sensitive to the indirect effects of COVID-19,” Janine E. Zee-Cheng, MD, adjunct clinical assistant professor of pediatrics in the department of pediatrics at Indiana University School of Medicine, Indianapolis, and colleagues wrote.
The full article, Pediatric ICU admissions significantly decreased during COVID-19 pandemic, can be found on the Healio website.
CHEST news
CHEST also recently issued a handful of statements and press releases on a variety of topics including the spread of misinformation, support of mandatory vaccinations for health care workers, and a statement advocating for broader coverage of supplemental oxygen use.
For all recent CHEST News, including these statements, visit the CHEST Newsroom on the CHEST website and follow the hashtag #CHESTNews on Twitter.
If you have been included in a recent news article and would like it to be featured, send the coverage to media@chestnet.org.
Creating a stronger voice for CHEST members in pulmonary, critical care, and sleep medicine, CHEST works to provide opportunities for members to serve as expert sources for both mainstream and trade media.
Below are a few highlights of media coverage from the past few months that work to expand awareness of CHEST and to promote the expertise of CHEST members in the media.
The New York Times covers the Philips recall
In August, a New York Times article published quoting incoming CHEST President, David Schulman, MD, MPH, FCCP. The article covered the recent Philips recall and its impact on the COVID-19 pandemic.
Dr. Schulman is quoted saying, “Because the number of people coming into the hospital with severe respiratory symptoms has increased as a result of COVID-19, the demand for these devices has also increased, which is problematic since available supply has decreased as a result of the Philips recall.”
The full article, Breathing Machine Recall Over Possible Cancer Risk Leaves Millions Scrambling for Substitutes, can be found on the New York Times website.
Technical expert panel on coverage determinations
Peter Gay, MD, FCCP, was quoted in an article by McKnight’s Long-Term Care News on the recent technical expert panel recommendations for national coverage determinations for optimal noninvasive ventilation.
“Centers for Medicare & Medicaid Services was wanting rigorous scientific support necessary to clarify the ‘reasonable and necessary’ role of these new mechanical therapeutic modalities where there was none in order to move forward,” said Dr. Gay. “What we have done is create a pathway to simplify the maze of regulation and perhaps most importantly, remove the obstacles that currently exist.”
The full article, Panel on Non-Invasive Ventilation Seeks to Simplify ‘Maze’ of Regulation for Device Coverage, can be found on the McKnight’s Long-Term Care News website.
Asthma and HRT
Originally appearing in HealthDay, U.S. News and World Report covered a recent journal CHEST® publication Hormone Replacement Therapy and Development of New Asthma by Erik Soeren Halvard Hansen, MD, et al.
The study included about 34,500 women who were diagnosed with asthma between 1995 and 2018, when they were 40 to 65 years of age. Each was then compared with 10 asthma-free women.
Based on that comparison, HRT use was associated with a 63% higher risk for developing asthma, according to the study.
The full article, HRT Could Raise Odds for Asthma, can be found on the U.S. News & World Report website.
Pediatric ICU admission and COVID-19
Healio Pulmonology covered a recent journal CHEST publication, Changes in Pediatric ICU Utilization and Clinical Trends During the Coronavirus Pandemic, by Janine E. Zee-Cheng, MD, et al.
“Severe infections, traumatic injuries, perioperative conditions and acute exacerbations of chronic illnesses such as asthma and diabetes are among the most common causes of admission to a pediatric ICU; thus, the epidemiology of pediatric critical illness was likely sensitive to the indirect effects of COVID-19,” Janine E. Zee-Cheng, MD, adjunct clinical assistant professor of pediatrics in the department of pediatrics at Indiana University School of Medicine, Indianapolis, and colleagues wrote.
The full article, Pediatric ICU admissions significantly decreased during COVID-19 pandemic, can be found on the Healio website.
CHEST news
CHEST also recently issued a handful of statements and press releases on a variety of topics including the spread of misinformation, support of mandatory vaccinations for health care workers, and a statement advocating for broader coverage of supplemental oxygen use.
For all recent CHEST News, including these statements, visit the CHEST Newsroom on the CHEST website and follow the hashtag #CHESTNews on Twitter.
If you have been included in a recent news article and would like it to be featured, send the coverage to media@chestnet.org.
Creating a stronger voice for CHEST members in pulmonary, critical care, and sleep medicine, CHEST works to provide opportunities for members to serve as expert sources for both mainstream and trade media.
Below are a few highlights of media coverage from the past few months that work to expand awareness of CHEST and to promote the expertise of CHEST members in the media.
The New York Times covers the Philips recall
In August, a New York Times article published quoting incoming CHEST President, David Schulman, MD, MPH, FCCP. The article covered the recent Philips recall and its impact on the COVID-19 pandemic.
Dr. Schulman is quoted saying, “Because the number of people coming into the hospital with severe respiratory symptoms has increased as a result of COVID-19, the demand for these devices has also increased, which is problematic since available supply has decreased as a result of the Philips recall.”
The full article, Breathing Machine Recall Over Possible Cancer Risk Leaves Millions Scrambling for Substitutes, can be found on the New York Times website.
Technical expert panel on coverage determinations
Peter Gay, MD, FCCP, was quoted in an article by McKnight’s Long-Term Care News on the recent technical expert panel recommendations for national coverage determinations for optimal noninvasive ventilation.
“Centers for Medicare & Medicaid Services was wanting rigorous scientific support necessary to clarify the ‘reasonable and necessary’ role of these new mechanical therapeutic modalities where there was none in order to move forward,” said Dr. Gay. “What we have done is create a pathway to simplify the maze of regulation and perhaps most importantly, remove the obstacles that currently exist.”
The full article, Panel on Non-Invasive Ventilation Seeks to Simplify ‘Maze’ of Regulation for Device Coverage, can be found on the McKnight’s Long-Term Care News website.
Asthma and HRT
Originally appearing in HealthDay, U.S. News and World Report covered a recent journal CHEST® publication Hormone Replacement Therapy and Development of New Asthma by Erik Soeren Halvard Hansen, MD, et al.
The study included about 34,500 women who were diagnosed with asthma between 1995 and 2018, when they were 40 to 65 years of age. Each was then compared with 10 asthma-free women.
Based on that comparison, HRT use was associated with a 63% higher risk for developing asthma, according to the study.
The full article, HRT Could Raise Odds for Asthma, can be found on the U.S. News & World Report website.
Pediatric ICU admission and COVID-19
Healio Pulmonology covered a recent journal CHEST publication, Changes in Pediatric ICU Utilization and Clinical Trends During the Coronavirus Pandemic, by Janine E. Zee-Cheng, MD, et al.
“Severe infections, traumatic injuries, perioperative conditions and acute exacerbations of chronic illnesses such as asthma and diabetes are among the most common causes of admission to a pediatric ICU; thus, the epidemiology of pediatric critical illness was likely sensitive to the indirect effects of COVID-19,” Janine E. Zee-Cheng, MD, adjunct clinical assistant professor of pediatrics in the department of pediatrics at Indiana University School of Medicine, Indianapolis, and colleagues wrote.
The full article, Pediatric ICU admissions significantly decreased during COVID-19 pandemic, can be found on the Healio website.
CHEST news
CHEST also recently issued a handful of statements and press releases on a variety of topics including the spread of misinformation, support of mandatory vaccinations for health care workers, and a statement advocating for broader coverage of supplemental oxygen use.
For all recent CHEST News, including these statements, visit the CHEST Newsroom on the CHEST website and follow the hashtag #CHESTNews on Twitter.
If you have been included in a recent news article and would like it to be featured, send the coverage to media@chestnet.org.
Finding your passion in fellowship
(This post is part of Our Life as a Fellow blog post series. This series includes “fellow life lessons” from current trainees in leadership with CHEST.)
Finding your passion in fellowship is an integral part of career development and has a profound impact on a young professional’s personal satisfaction. This can be a difficult task, but it can be accomplished by finding a mentor, thinking about long-term career goals, and considering what re-energizes you. Entering fellowship, some may have a preconceived idea of who they would like to be upon completion of training: An asthma specialist, a physician-scientist, a critical care junkie, etc. For most of us, fellowship is a black box of opportunity with endless paths and permutations. It can be difficult to navigate this landscape, as the path may meander and a few initial interests may develop into true passions.
During my fellowship, I have been fortunate to have had many great teachers and experiences caring for patients with pulmonary hypertension, my current primary focus. Here are a few steps I have taken in pursuit of finding my passion over the past several years of post-graduate medical education. ***Disclaimer: I am still a work in progress.***
First, find a mentor. For me it was easy – I remember interviewing for fellowship with my mentor and thinking: “That is who I want to be.” I think this is hugely important. Use the insights, mistakes, and successes of someone you admire (from near or far) to help guide you. Initially, while getting to know my mentor, it was more comfortable to follow from a safe distance without making an official commitment. This was a slow process that allowed me to explore multiple clinical and research interests simultaneously. Once your mind is set, stating your professional interests in a concise way helps you and your mentor define and differentiate hobbies from passions. The practice of medicine is still very much an apprenticeship, so having someone to act as a sounding board remains important. Mentorship is also critical for networking, which is important for professional growth and life beyond fellowship. Our community is small, and “people know people.” What happens if you can’t find a perfect mentor? Don’t worry! Try out as many mentors as you can find. You can learn from every conversation and relationship. Sometimes the path taken is just as important as the destination.
Second, think about your 5- or 10-year plan. Ultimately, when training is over, we will graduate from fellowship and be released into the wild. The skills we have obtained in training are going to be the foundation for the rest of our careers. Where would you like to be a few years post-training? In a lab? Private practice? Rural medicine? Teaching? Does the energy you are spending in fellowship to develop your passion extend beyond fellowship? Part of the excitement of pursuing a passion is envisioning how it may develop over the period of coming years. I envision honing my skills as a master general pulmonary clinician and then narrowing my focus to create a pulmonary hypertension care center of excellence. I think these are important points to consider while you have the protected headspace of fellowship to experiment and explore, and while you are not constrained by contractual obligations.
Third, think about what personally and professionally energizes you. Especially in the context of an ongoing global pandemic, burnout and physician dissatisfaction are at an all-time high. Acknowledge that your job is tough, and try to identify the things that will keep the engine running. This sounds straightforward, but you have to decide what recharges you and acknowledge those things that don’t. The importance of determining things that energize me did not occur to me until I started searching for my first job. This forced me to make a list of things that contributed to my happiness and dissatisfaction. Most future employers are skilled at asking about these qualities. A happy employee is productive and effective at his or her job!
If you are in training, take some time to get creative and answer the questions above. Doodle, make lists, or journal—find a moment to reflect on your hard work and on the promise of your future.
Kevin Swiatek, DO
Dr. Swiatek is a third-year Chief Fellow in the Division of Pulmonary and Critical Care Medicine at Virginia Commonwealth University in Richmond, Virginia. Dr. Swiatek is a member of the CHEST Trainee Work Group. His clinical interests include general pulmonary medicine, care of patients with pulmonary hypertension, and using point-of-care ultrasound (POCUS) as a diagnostic tool in the medical intensive care unit. His scholarly interests include implementation of fellowship medical education, teaching POCUS, and clinical and diagnostic assessment of patients with pulmonary hypertension.
Reprinted from Thought Leader Blog. August 23, 2021. www.chestnet.org.
(This post is part of Our Life as a Fellow blog post series. This series includes “fellow life lessons” from current trainees in leadership with CHEST.)
Finding your passion in fellowship is an integral part of career development and has a profound impact on a young professional’s personal satisfaction. This can be a difficult task, but it can be accomplished by finding a mentor, thinking about long-term career goals, and considering what re-energizes you. Entering fellowship, some may have a preconceived idea of who they would like to be upon completion of training: An asthma specialist, a physician-scientist, a critical care junkie, etc. For most of us, fellowship is a black box of opportunity with endless paths and permutations. It can be difficult to navigate this landscape, as the path may meander and a few initial interests may develop into true passions.
During my fellowship, I have been fortunate to have had many great teachers and experiences caring for patients with pulmonary hypertension, my current primary focus. Here are a few steps I have taken in pursuit of finding my passion over the past several years of post-graduate medical education. ***Disclaimer: I am still a work in progress.***
First, find a mentor. For me it was easy – I remember interviewing for fellowship with my mentor and thinking: “That is who I want to be.” I think this is hugely important. Use the insights, mistakes, and successes of someone you admire (from near or far) to help guide you. Initially, while getting to know my mentor, it was more comfortable to follow from a safe distance without making an official commitment. This was a slow process that allowed me to explore multiple clinical and research interests simultaneously. Once your mind is set, stating your professional interests in a concise way helps you and your mentor define and differentiate hobbies from passions. The practice of medicine is still very much an apprenticeship, so having someone to act as a sounding board remains important. Mentorship is also critical for networking, which is important for professional growth and life beyond fellowship. Our community is small, and “people know people.” What happens if you can’t find a perfect mentor? Don’t worry! Try out as many mentors as you can find. You can learn from every conversation and relationship. Sometimes the path taken is just as important as the destination.
Second, think about your 5- or 10-year plan. Ultimately, when training is over, we will graduate from fellowship and be released into the wild. The skills we have obtained in training are going to be the foundation for the rest of our careers. Where would you like to be a few years post-training? In a lab? Private practice? Rural medicine? Teaching? Does the energy you are spending in fellowship to develop your passion extend beyond fellowship? Part of the excitement of pursuing a passion is envisioning how it may develop over the period of coming years. I envision honing my skills as a master general pulmonary clinician and then narrowing my focus to create a pulmonary hypertension care center of excellence. I think these are important points to consider while you have the protected headspace of fellowship to experiment and explore, and while you are not constrained by contractual obligations.
Third, think about what personally and professionally energizes you. Especially in the context of an ongoing global pandemic, burnout and physician dissatisfaction are at an all-time high. Acknowledge that your job is tough, and try to identify the things that will keep the engine running. This sounds straightforward, but you have to decide what recharges you and acknowledge those things that don’t. The importance of determining things that energize me did not occur to me until I started searching for my first job. This forced me to make a list of things that contributed to my happiness and dissatisfaction. Most future employers are skilled at asking about these qualities. A happy employee is productive and effective at his or her job!
If you are in training, take some time to get creative and answer the questions above. Doodle, make lists, or journal—find a moment to reflect on your hard work and on the promise of your future.
Kevin Swiatek, DO
Dr. Swiatek is a third-year Chief Fellow in the Division of Pulmonary and Critical Care Medicine at Virginia Commonwealth University in Richmond, Virginia. Dr. Swiatek is a member of the CHEST Trainee Work Group. His clinical interests include general pulmonary medicine, care of patients with pulmonary hypertension, and using point-of-care ultrasound (POCUS) as a diagnostic tool in the medical intensive care unit. His scholarly interests include implementation of fellowship medical education, teaching POCUS, and clinical and diagnostic assessment of patients with pulmonary hypertension.
Reprinted from Thought Leader Blog. August 23, 2021. www.chestnet.org.
(This post is part of Our Life as a Fellow blog post series. This series includes “fellow life lessons” from current trainees in leadership with CHEST.)
Finding your passion in fellowship is an integral part of career development and has a profound impact on a young professional’s personal satisfaction. This can be a difficult task, but it can be accomplished by finding a mentor, thinking about long-term career goals, and considering what re-energizes you. Entering fellowship, some may have a preconceived idea of who they would like to be upon completion of training: An asthma specialist, a physician-scientist, a critical care junkie, etc. For most of us, fellowship is a black box of opportunity with endless paths and permutations. It can be difficult to navigate this landscape, as the path may meander and a few initial interests may develop into true passions.
During my fellowship, I have been fortunate to have had many great teachers and experiences caring for patients with pulmonary hypertension, my current primary focus. Here are a few steps I have taken in pursuit of finding my passion over the past several years of post-graduate medical education. ***Disclaimer: I am still a work in progress.***
First, find a mentor. For me it was easy – I remember interviewing for fellowship with my mentor and thinking: “That is who I want to be.” I think this is hugely important. Use the insights, mistakes, and successes of someone you admire (from near or far) to help guide you. Initially, while getting to know my mentor, it was more comfortable to follow from a safe distance without making an official commitment. This was a slow process that allowed me to explore multiple clinical and research interests simultaneously. Once your mind is set, stating your professional interests in a concise way helps you and your mentor define and differentiate hobbies from passions. The practice of medicine is still very much an apprenticeship, so having someone to act as a sounding board remains important. Mentorship is also critical for networking, which is important for professional growth and life beyond fellowship. Our community is small, and “people know people.” What happens if you can’t find a perfect mentor? Don’t worry! Try out as many mentors as you can find. You can learn from every conversation and relationship. Sometimes the path taken is just as important as the destination.
Second, think about your 5- or 10-year plan. Ultimately, when training is over, we will graduate from fellowship and be released into the wild. The skills we have obtained in training are going to be the foundation for the rest of our careers. Where would you like to be a few years post-training? In a lab? Private practice? Rural medicine? Teaching? Does the energy you are spending in fellowship to develop your passion extend beyond fellowship? Part of the excitement of pursuing a passion is envisioning how it may develop over the period of coming years. I envision honing my skills as a master general pulmonary clinician and then narrowing my focus to create a pulmonary hypertension care center of excellence. I think these are important points to consider while you have the protected headspace of fellowship to experiment and explore, and while you are not constrained by contractual obligations.
Third, think about what personally and professionally energizes you. Especially in the context of an ongoing global pandemic, burnout and physician dissatisfaction are at an all-time high. Acknowledge that your job is tough, and try to identify the things that will keep the engine running. This sounds straightforward, but you have to decide what recharges you and acknowledge those things that don’t. The importance of determining things that energize me did not occur to me until I started searching for my first job. This forced me to make a list of things that contributed to my happiness and dissatisfaction. Most future employers are skilled at asking about these qualities. A happy employee is productive and effective at his or her job!
If you are in training, take some time to get creative and answer the questions above. Doodle, make lists, or journal—find a moment to reflect on your hard work and on the promise of your future.
Kevin Swiatek, DO
Dr. Swiatek is a third-year Chief Fellow in the Division of Pulmonary and Critical Care Medicine at Virginia Commonwealth University in Richmond, Virginia. Dr. Swiatek is a member of the CHEST Trainee Work Group. His clinical interests include general pulmonary medicine, care of patients with pulmonary hypertension, and using point-of-care ultrasound (POCUS) as a diagnostic tool in the medical intensive care unit. His scholarly interests include implementation of fellowship medical education, teaching POCUS, and clinical and diagnostic assessment of patients with pulmonary hypertension.
Reprinted from Thought Leader Blog. August 23, 2021. www.chestnet.org.
The apnea-hypopnea index: Limitations and future directions
Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse resulting in intermittent hypoxemia and hypercapnia, large intrathoracic pressure swings, and cortical arousals. The rate of apneas and hypopneas observed during sleep, the apnea-hypopnea index (AHI), has been used for decades to diagnose OSA and to classify its severity. Despite the wide acceptance of this metric by the sleep medicine community, clinical research has found poor correlations between the AHI- and OSA-related complications or symptoms. We have come to learn that the AHI is an oversimplification of a complex and diverse disease process. (Punjabi. Chest. 2016;149[1]:16-9).
The most important features of a disease metric are reliability, and the ability to predict clinically relevant outcomes. The reliability of the AHI has been in question due to substantial night-to-night variability that can lead to missed diagnosis and disease severity misclassification (Dzierzewski et al. J Clin Sleep Med. 2020;16[4]:539-44). Furthermore, the AHI fails to reflect some important physiologic derangements resulting from respiratory events. Apart from imperfectly set thresholds for scoring, it disregards the depth and the duration of ventilatory disturbances. For example, a hypopnea lasting 30 seconds and resulting in a decrease of 10% in oxyhemoglobin saturation is considered equivalent to a hypopnea lasting 10 seconds and resulting in a decrease of 4% in oxyhemoglobin saturation. The AHI also assumes that apneas and hypopneas are equal in their biological effects regardless of when they occur during sleep (NREM vs REM), despite reports suggesting that the sequalae of OSA are sleep-stage dependent (Varga, Mokhlesi. Sleep Breath. 2019;23[2]:413-23). This is further complicated by the varying hypopnea definitions and the difficulties in differentiating obstructive vs central hypopneas. It is doubtful that these events, which differ in mechanism, would result in similar outcomes.
Over the past decade, our understanding of the different pathophysiological mechanisms leading to OSA has grown substantially, suggesting the need for a phenotype-specific treatment approach (Zinchuk, Yaggi. Chest. 2020;157[2]:403-20). The reliance on a single metric that does not capture this heterogeneity may prove detrimental to our therapeutic efforts. One extremely important dimension that is missed by the AHI is the patient. Individual response to airway obstruction varies with age, genetics, gender, and comorbidities, among other things. This may explain the difference in symptoms and outcomes experienced by patients with the same AHI. During the era of precision medicine, the concept of defining a clinical condition by a single test result, without regard to patient characteristics, is antiquated.
Several studies have attempted to propose complementary metrics that may better characterize OSA and predict outcomes. The hypoxic burden has gained a lot of attention as it is generally felt that hypoxemia is a major factor contributing to the pathogenesis of OSA-related comorbidities. Azarbarzin, et al. reported a hypoxic burden metric by measuring the area under the oxygen desaturation curve during a respiratory event (Azarbarzin et al. Eur Heart J. 2019;40[14]:1149-57). It factors the length and depth of the desaturations into a single value that expresses the average desaturation burden per hour of sleep time. The hypoxic burden was independently predictive of cardiovascular mortality in two large cohorts. Interestingly, the AHI did not have such an association. Similarly, another novel proposed parameter, the oxygen desaturation rate (ODR), outperformed the AHI in predicting cardiovascular outcomes in severe OSA patients (Wang et al. J Clin Sleep Med. 2020;16[7]:1055-62). The ODR measures the speed of an oxygen desaturation during an apnea event. Subjects with a faster ODR were found to have higher blood pressure values and variability. The authors hypothesized that slower desaturations generate hypoxemia-conditioning that may protect from exaggerated hemodynamic changes. These findings of novel hypoxemia metrics, albeit having their own limitations, recapitulate the need to move beyond the AHI to characterize OSA.
The apnea-hypopnea event duration is another overlooked feature that may impact OSA outcomes. Butler, et al. demonstrated that shorter event duration predicted a higher all-cause mortality over and beyond that predicted by AHI (Butler et al. Am J Respir Crit Care Med. 2019;199[7]:903-12). These results contrast views that early arousals in response to respiratory events may improve outcomes as they reflect a protective mechanism to prevent further hypoxemia and sympatho-excitation. For example, Ma, et al. found that higher percentage of total sleep time spent in apnea/hypopnea (AHT%) predicted worse daytime sleepiness to a higher degree than standard AHI (Ma et al. Sci Rep. 2021;11[1]:4702). However, shorter event duration may represent lower arousal thresholds (increased excitability), and ventilatory control instability (higher loop gain), predisposing patients to augmented sympathetic activity. Along similar lines, the intensity of respiratory-related arousals (as measured by EEG wavelet transformation) was found to be independent of preceding respiratory stimulus, with higher arousal intensity levels correlating with higher respiratory and heart rate responses (Amatoury et al. Sleep. 2016;39[12]:2091-100). The contribution of arousals to OSA morbidity is of particular importance for women in whom long-term outcomes of elevated AHI are poorly understood. Bearing in mind the differences in the metrics used, these results underscore the role of event duration and arousability in the pathogenesis of OSA-related morbidity.
The AHI is certainly an important piece of data that is informative and somewhat predictive. However, when used as a sole disease-defining metric, it has yielded disappointing results, especially after OSA treatment trials failed to show cardiovascular benefits despite therapies achieving a low residual AHI. As we aim to achieve a more personalized approach for diagnosing and treating OSA, we need to explore beyond the concept of a single metric to define a heterogenous and complex disorder. Instead of relying on the frequency of respiratory events, it is time to use complementary polysomnographic data that better reflect the origin and systemic effects of these disturbances. Machine-learning methods may offer sophisticated approaches to identifying polysomnographic patterns for future research. Clinical characteristics will also likely need to be considered in OSA severity scales. The identification of symptom subtypes or blood biomarkers may help identify patient groups who may be impacted differently by OSA, and consequently have a different treatment response (Malhotra et al. Sleep. 2021;44[7]:zsab030).
Almost half a century has lapsed since the original descriptions of OSA. Since then, our understanding of the disorder has improved greatly, with much still to be discovered, but our method of disease capture is unwavering. Future research requires a focus on novel measures aimed at identifying OSA endophenotypes, which will transform our understanding of disease traits and propel us into personalized therapies.
Dr. Mansour is Assistant Professor of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina. Dr. Won is Associate Professor of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine; and VA Connecticut Healthcare System, West Haven, Connecticut.
Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse resulting in intermittent hypoxemia and hypercapnia, large intrathoracic pressure swings, and cortical arousals. The rate of apneas and hypopneas observed during sleep, the apnea-hypopnea index (AHI), has been used for decades to diagnose OSA and to classify its severity. Despite the wide acceptance of this metric by the sleep medicine community, clinical research has found poor correlations between the AHI- and OSA-related complications or symptoms. We have come to learn that the AHI is an oversimplification of a complex and diverse disease process. (Punjabi. Chest. 2016;149[1]:16-9).
The most important features of a disease metric are reliability, and the ability to predict clinically relevant outcomes. The reliability of the AHI has been in question due to substantial night-to-night variability that can lead to missed diagnosis and disease severity misclassification (Dzierzewski et al. J Clin Sleep Med. 2020;16[4]:539-44). Furthermore, the AHI fails to reflect some important physiologic derangements resulting from respiratory events. Apart from imperfectly set thresholds for scoring, it disregards the depth and the duration of ventilatory disturbances. For example, a hypopnea lasting 30 seconds and resulting in a decrease of 10% in oxyhemoglobin saturation is considered equivalent to a hypopnea lasting 10 seconds and resulting in a decrease of 4% in oxyhemoglobin saturation. The AHI also assumes that apneas and hypopneas are equal in their biological effects regardless of when they occur during sleep (NREM vs REM), despite reports suggesting that the sequalae of OSA are sleep-stage dependent (Varga, Mokhlesi. Sleep Breath. 2019;23[2]:413-23). This is further complicated by the varying hypopnea definitions and the difficulties in differentiating obstructive vs central hypopneas. It is doubtful that these events, which differ in mechanism, would result in similar outcomes.
Over the past decade, our understanding of the different pathophysiological mechanisms leading to OSA has grown substantially, suggesting the need for a phenotype-specific treatment approach (Zinchuk, Yaggi. Chest. 2020;157[2]:403-20). The reliance on a single metric that does not capture this heterogeneity may prove detrimental to our therapeutic efforts. One extremely important dimension that is missed by the AHI is the patient. Individual response to airway obstruction varies with age, genetics, gender, and comorbidities, among other things. This may explain the difference in symptoms and outcomes experienced by patients with the same AHI. During the era of precision medicine, the concept of defining a clinical condition by a single test result, without regard to patient characteristics, is antiquated.
Several studies have attempted to propose complementary metrics that may better characterize OSA and predict outcomes. The hypoxic burden has gained a lot of attention as it is generally felt that hypoxemia is a major factor contributing to the pathogenesis of OSA-related comorbidities. Azarbarzin, et al. reported a hypoxic burden metric by measuring the area under the oxygen desaturation curve during a respiratory event (Azarbarzin et al. Eur Heart J. 2019;40[14]:1149-57). It factors the length and depth of the desaturations into a single value that expresses the average desaturation burden per hour of sleep time. The hypoxic burden was independently predictive of cardiovascular mortality in two large cohorts. Interestingly, the AHI did not have such an association. Similarly, another novel proposed parameter, the oxygen desaturation rate (ODR), outperformed the AHI in predicting cardiovascular outcomes in severe OSA patients (Wang et al. J Clin Sleep Med. 2020;16[7]:1055-62). The ODR measures the speed of an oxygen desaturation during an apnea event. Subjects with a faster ODR were found to have higher blood pressure values and variability. The authors hypothesized that slower desaturations generate hypoxemia-conditioning that may protect from exaggerated hemodynamic changes. These findings of novel hypoxemia metrics, albeit having their own limitations, recapitulate the need to move beyond the AHI to characterize OSA.
The apnea-hypopnea event duration is another overlooked feature that may impact OSA outcomes. Butler, et al. demonstrated that shorter event duration predicted a higher all-cause mortality over and beyond that predicted by AHI (Butler et al. Am J Respir Crit Care Med. 2019;199[7]:903-12). These results contrast views that early arousals in response to respiratory events may improve outcomes as they reflect a protective mechanism to prevent further hypoxemia and sympatho-excitation. For example, Ma, et al. found that higher percentage of total sleep time spent in apnea/hypopnea (AHT%) predicted worse daytime sleepiness to a higher degree than standard AHI (Ma et al. Sci Rep. 2021;11[1]:4702). However, shorter event duration may represent lower arousal thresholds (increased excitability), and ventilatory control instability (higher loop gain), predisposing patients to augmented sympathetic activity. Along similar lines, the intensity of respiratory-related arousals (as measured by EEG wavelet transformation) was found to be independent of preceding respiratory stimulus, with higher arousal intensity levels correlating with higher respiratory and heart rate responses (Amatoury et al. Sleep. 2016;39[12]:2091-100). The contribution of arousals to OSA morbidity is of particular importance for women in whom long-term outcomes of elevated AHI are poorly understood. Bearing in mind the differences in the metrics used, these results underscore the role of event duration and arousability in the pathogenesis of OSA-related morbidity.
The AHI is certainly an important piece of data that is informative and somewhat predictive. However, when used as a sole disease-defining metric, it has yielded disappointing results, especially after OSA treatment trials failed to show cardiovascular benefits despite therapies achieving a low residual AHI. As we aim to achieve a more personalized approach for diagnosing and treating OSA, we need to explore beyond the concept of a single metric to define a heterogenous and complex disorder. Instead of relying on the frequency of respiratory events, it is time to use complementary polysomnographic data that better reflect the origin and systemic effects of these disturbances. Machine-learning methods may offer sophisticated approaches to identifying polysomnographic patterns for future research. Clinical characteristics will also likely need to be considered in OSA severity scales. The identification of symptom subtypes or blood biomarkers may help identify patient groups who may be impacted differently by OSA, and consequently have a different treatment response (Malhotra et al. Sleep. 2021;44[7]:zsab030).
Almost half a century has lapsed since the original descriptions of OSA. Since then, our understanding of the disorder has improved greatly, with much still to be discovered, but our method of disease capture is unwavering. Future research requires a focus on novel measures aimed at identifying OSA endophenotypes, which will transform our understanding of disease traits and propel us into personalized therapies.
Dr. Mansour is Assistant Professor of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina. Dr. Won is Associate Professor of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine; and VA Connecticut Healthcare System, West Haven, Connecticut.
Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse resulting in intermittent hypoxemia and hypercapnia, large intrathoracic pressure swings, and cortical arousals. The rate of apneas and hypopneas observed during sleep, the apnea-hypopnea index (AHI), has been used for decades to diagnose OSA and to classify its severity. Despite the wide acceptance of this metric by the sleep medicine community, clinical research has found poor correlations between the AHI- and OSA-related complications or symptoms. We have come to learn that the AHI is an oversimplification of a complex and diverse disease process. (Punjabi. Chest. 2016;149[1]:16-9).
The most important features of a disease metric are reliability, and the ability to predict clinically relevant outcomes. The reliability of the AHI has been in question due to substantial night-to-night variability that can lead to missed diagnosis and disease severity misclassification (Dzierzewski et al. J Clin Sleep Med. 2020;16[4]:539-44). Furthermore, the AHI fails to reflect some important physiologic derangements resulting from respiratory events. Apart from imperfectly set thresholds for scoring, it disregards the depth and the duration of ventilatory disturbances. For example, a hypopnea lasting 30 seconds and resulting in a decrease of 10% in oxyhemoglobin saturation is considered equivalent to a hypopnea lasting 10 seconds and resulting in a decrease of 4% in oxyhemoglobin saturation. The AHI also assumes that apneas and hypopneas are equal in their biological effects regardless of when they occur during sleep (NREM vs REM), despite reports suggesting that the sequalae of OSA are sleep-stage dependent (Varga, Mokhlesi. Sleep Breath. 2019;23[2]:413-23). This is further complicated by the varying hypopnea definitions and the difficulties in differentiating obstructive vs central hypopneas. It is doubtful that these events, which differ in mechanism, would result in similar outcomes.
Over the past decade, our understanding of the different pathophysiological mechanisms leading to OSA has grown substantially, suggesting the need for a phenotype-specific treatment approach (Zinchuk, Yaggi. Chest. 2020;157[2]:403-20). The reliance on a single metric that does not capture this heterogeneity may prove detrimental to our therapeutic efforts. One extremely important dimension that is missed by the AHI is the patient. Individual response to airway obstruction varies with age, genetics, gender, and comorbidities, among other things. This may explain the difference in symptoms and outcomes experienced by patients with the same AHI. During the era of precision medicine, the concept of defining a clinical condition by a single test result, without regard to patient characteristics, is antiquated.
Several studies have attempted to propose complementary metrics that may better characterize OSA and predict outcomes. The hypoxic burden has gained a lot of attention as it is generally felt that hypoxemia is a major factor contributing to the pathogenesis of OSA-related comorbidities. Azarbarzin, et al. reported a hypoxic burden metric by measuring the area under the oxygen desaturation curve during a respiratory event (Azarbarzin et al. Eur Heart J. 2019;40[14]:1149-57). It factors the length and depth of the desaturations into a single value that expresses the average desaturation burden per hour of sleep time. The hypoxic burden was independently predictive of cardiovascular mortality in two large cohorts. Interestingly, the AHI did not have such an association. Similarly, another novel proposed parameter, the oxygen desaturation rate (ODR), outperformed the AHI in predicting cardiovascular outcomes in severe OSA patients (Wang et al. J Clin Sleep Med. 2020;16[7]:1055-62). The ODR measures the speed of an oxygen desaturation during an apnea event. Subjects with a faster ODR were found to have higher blood pressure values and variability. The authors hypothesized that slower desaturations generate hypoxemia-conditioning that may protect from exaggerated hemodynamic changes. These findings of novel hypoxemia metrics, albeit having their own limitations, recapitulate the need to move beyond the AHI to characterize OSA.
The apnea-hypopnea event duration is another overlooked feature that may impact OSA outcomes. Butler, et al. demonstrated that shorter event duration predicted a higher all-cause mortality over and beyond that predicted by AHI (Butler et al. Am J Respir Crit Care Med. 2019;199[7]:903-12). These results contrast views that early arousals in response to respiratory events may improve outcomes as they reflect a protective mechanism to prevent further hypoxemia and sympatho-excitation. For example, Ma, et al. found that higher percentage of total sleep time spent in apnea/hypopnea (AHT%) predicted worse daytime sleepiness to a higher degree than standard AHI (Ma et al. Sci Rep. 2021;11[1]:4702). However, shorter event duration may represent lower arousal thresholds (increased excitability), and ventilatory control instability (higher loop gain), predisposing patients to augmented sympathetic activity. Along similar lines, the intensity of respiratory-related arousals (as measured by EEG wavelet transformation) was found to be independent of preceding respiratory stimulus, with higher arousal intensity levels correlating with higher respiratory and heart rate responses (Amatoury et al. Sleep. 2016;39[12]:2091-100). The contribution of arousals to OSA morbidity is of particular importance for women in whom long-term outcomes of elevated AHI are poorly understood. Bearing in mind the differences in the metrics used, these results underscore the role of event duration and arousability in the pathogenesis of OSA-related morbidity.
The AHI is certainly an important piece of data that is informative and somewhat predictive. However, when used as a sole disease-defining metric, it has yielded disappointing results, especially after OSA treatment trials failed to show cardiovascular benefits despite therapies achieving a low residual AHI. As we aim to achieve a more personalized approach for diagnosing and treating OSA, we need to explore beyond the concept of a single metric to define a heterogenous and complex disorder. Instead of relying on the frequency of respiratory events, it is time to use complementary polysomnographic data that better reflect the origin and systemic effects of these disturbances. Machine-learning methods may offer sophisticated approaches to identifying polysomnographic patterns for future research. Clinical characteristics will also likely need to be considered in OSA severity scales. The identification of symptom subtypes or blood biomarkers may help identify patient groups who may be impacted differently by OSA, and consequently have a different treatment response (Malhotra et al. Sleep. 2021;44[7]:zsab030).
Almost half a century has lapsed since the original descriptions of OSA. Since then, our understanding of the disorder has improved greatly, with much still to be discovered, but our method of disease capture is unwavering. Future research requires a focus on novel measures aimed at identifying OSA endophenotypes, which will transform our understanding of disease traits and propel us into personalized therapies.
Dr. Mansour is Assistant Professor of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, North Carolina. Dr. Won is Associate Professor of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine; and VA Connecticut Healthcare System, West Haven, Connecticut.
Seborrheic dermatitis
THE COMPARISON
A Seborrheic dermatitis in a woman with brown-gray greasy scale, as well as petaloid papules and plaques that are especially prominent in the nasolabial folds.
B Seborrheic dermatitis in a man with erythema, scale, and mild postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.
C Seborrheic dermatitis in a man with erythema, faint scale, and postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.
D Seborrheic dermatitis in a man with erythema and scale of the eyebrows and glabellar region.
Seborrheic dermatitis (SD) is an inflammatory condition that is thought to be part of a response to Malassezia yeast. The scalp and face are most commonly affected, particularly the nasolabial folds, eyebrows, ears, postauricular areas, and beard area. Men also may have SD on the mid upper chest in association with chest hair. In infants, the scalp and body skin folds often are affected.
Epidemiology
SD affects patients of all ages: infants, adolescents, and adults. It is among the most common dermatologic diagnoses reported in Black patients in the United States.1
Key clinical features in darker skin tones
- In those with darker skin tones, arcuate, polycyclic, or petaloid (flower petallike) plaques may be present (FIGURE A). Also, hypopigmented patches and plaques may be prominent (FIGURES B AND C). The classic description includes thin pink patches and plaques with white greasy scale on the face (FIGURE D).
- The scalp may have diffuse scale or isolated scaly plaques.
Worth noting
- In those with tightly coiled hair, there is a predisposition for dry hair and increased risk for breakage.
- Treatment plans for patients with SD often include frequent hair washing. However, in those with tightly coiled hair, the treatment plan may need to be modified due to hair texture, tendency for dryness, and washing frequency preferences. Washing the scalp at least every 1 to 2 weeks may be a preferred approach for those with tightly coiled hair at increased risk for dryness/breakage vs washing daily.2 In a sample of 201 caregivers of Black girls, Rucker Wright et al3 found that washing the hair more than once per week was not correlated with a lower prevalence of SD.
- If tightly coiled hair is temporarily straightened with heat (eg, blow-dryer, flat iron), adding a liquid-based treatment such as clobetasol solution or fluocinonide solution will cause the hair to revert to its normal curl pattern.
- It is appropriate to ask patients for their vehicle preference for medications.2 For example, if clobetasol is the treatment selected for the patient, the vehicle can reflect patient preference for a liquid, foam, cream, or ointment.
- Some antifungal/antiyeast shampoos may cause further hair dryness and breakage.
- Treatment may be delayed because patients often use various topical pomades and ointments to cover up the scale and help with pruritus.
- Diffuse scale of tinea capitis in school- aged children can be mistaken for SD, which leads to delayed diagnosis and treatment.
- Clinicians should become comfortable with scalp examinations in patients with tightly coiled hair. Patients with chief concerns related to their hair and scalp expect their clinicians to touch these areas. Avoid leaning in to examine the patient without touching the patient’s hair and scalp.2,4
Health disparity highlight
SD is among the most common cutaneous disorders diagnosed in patients with skin of color.1,5 Delay in recognition of SD in those with darker skin tones leads to delayed treatment. SD of the face can cause notable postinflammatory pigmentation alteration. Pigmentation changes in the skin further impact quality of life.
1. Alexis AF, Sergay AB, Taylor SC. Common dermatologic disorders in skin of color: a comparative practice survey. Cutis. 2007;80:387-394.
2. Grayson C, Heath C. Tips for addressing common conditions affecting pediatric and adolescent patients with skin of color [published online March 2, 2021]. Pediatr Dermatol. 2021;10.1111/ pde.14525
3. Rucker Wright D, Gathers R, Kapke A, et al. Hair care practices and their association with scalp and hair disorders in African American girls. J Am Acad Dermatol. 2011;64: 253-262. doi:10.1016/j.jaad.2010.05.037
4. Grayson C, Heath C. An approach to examining tightly coiled hair among patients with hair loss in race-discordant patientphysician interactions. JAMA Dermatol. 2021;157:505-506. doi:10.1001/jamadermatol.2021.0338
5. Gaulding JV, Gutierrez D, Bhatia BK, et al. Epidemiology of skin diseases in a diverse patient population. J Drugs Dermatol. 2018;17:1032-1036.
Candrice R. Heath, MD
Department of Dermatology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA
Richard P. Usatine, MD
Family and Community Medicine, Dermatology and Cutaneous Surgery, University of Texas Health, San Antonio
The authors reported no potential conflict of interest relevant to this article.
Simultaneously published in Cutis and The Journal of Family Practice.
Candrice R. Heath, MD
Department of Dermatology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA
Richard P. Usatine, MD
Family and Community Medicine, Dermatology and Cutaneous Surgery, University of Texas Health, San Antonio
The authors reported no potential conflict of interest relevant to this article.
Simultaneously published in Cutis and The Journal of Family Practice.
Candrice R. Heath, MD
Department of Dermatology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA
Richard P. Usatine, MD
Family and Community Medicine, Dermatology and Cutaneous Surgery, University of Texas Health, San Antonio
The authors reported no potential conflict of interest relevant to this article.
Simultaneously published in Cutis and The Journal of Family Practice.
THE COMPARISON
A Seborrheic dermatitis in a woman with brown-gray greasy scale, as well as petaloid papules and plaques that are especially prominent in the nasolabial folds.
B Seborrheic dermatitis in a man with erythema, scale, and mild postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.
C Seborrheic dermatitis in a man with erythema, faint scale, and postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.
D Seborrheic dermatitis in a man with erythema and scale of the eyebrows and glabellar region.
Seborrheic dermatitis (SD) is an inflammatory condition that is thought to be part of a response to Malassezia yeast. The scalp and face are most commonly affected, particularly the nasolabial folds, eyebrows, ears, postauricular areas, and beard area. Men also may have SD on the mid upper chest in association with chest hair. In infants, the scalp and body skin folds often are affected.
Epidemiology
SD affects patients of all ages: infants, adolescents, and adults. It is among the most common dermatologic diagnoses reported in Black patients in the United States.1
Key clinical features in darker skin tones
- In those with darker skin tones, arcuate, polycyclic, or petaloid (flower petallike) plaques may be present (FIGURE A). Also, hypopigmented patches and plaques may be prominent (FIGURES B AND C). The classic description includes thin pink patches and plaques with white greasy scale on the face (FIGURE D).
- The scalp may have diffuse scale or isolated scaly plaques.
Worth noting
- In those with tightly coiled hair, there is a predisposition for dry hair and increased risk for breakage.
- Treatment plans for patients with SD often include frequent hair washing. However, in those with tightly coiled hair, the treatment plan may need to be modified due to hair texture, tendency for dryness, and washing frequency preferences. Washing the scalp at least every 1 to 2 weeks may be a preferred approach for those with tightly coiled hair at increased risk for dryness/breakage vs washing daily.2 In a sample of 201 caregivers of Black girls, Rucker Wright et al3 found that washing the hair more than once per week was not correlated with a lower prevalence of SD.
- If tightly coiled hair is temporarily straightened with heat (eg, blow-dryer, flat iron), adding a liquid-based treatment such as clobetasol solution or fluocinonide solution will cause the hair to revert to its normal curl pattern.
- It is appropriate to ask patients for their vehicle preference for medications.2 For example, if clobetasol is the treatment selected for the patient, the vehicle can reflect patient preference for a liquid, foam, cream, or ointment.
- Some antifungal/antiyeast shampoos may cause further hair dryness and breakage.
- Treatment may be delayed because patients often use various topical pomades and ointments to cover up the scale and help with pruritus.
- Diffuse scale of tinea capitis in school- aged children can be mistaken for SD, which leads to delayed diagnosis and treatment.
- Clinicians should become comfortable with scalp examinations in patients with tightly coiled hair. Patients with chief concerns related to their hair and scalp expect their clinicians to touch these areas. Avoid leaning in to examine the patient without touching the patient’s hair and scalp.2,4
Health disparity highlight
SD is among the most common cutaneous disorders diagnosed in patients with skin of color.1,5 Delay in recognition of SD in those with darker skin tones leads to delayed treatment. SD of the face can cause notable postinflammatory pigmentation alteration. Pigmentation changes in the skin further impact quality of life.
THE COMPARISON
A Seborrheic dermatitis in a woman with brown-gray greasy scale, as well as petaloid papules and plaques that are especially prominent in the nasolabial folds.
B Seborrheic dermatitis in a man with erythema, scale, and mild postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.
C Seborrheic dermatitis in a man with erythema, faint scale, and postinflammatory hypopigmentation that are especially prominent in the nasolabial folds.
D Seborrheic dermatitis in a man with erythema and scale of the eyebrows and glabellar region.
Seborrheic dermatitis (SD) is an inflammatory condition that is thought to be part of a response to Malassezia yeast. The scalp and face are most commonly affected, particularly the nasolabial folds, eyebrows, ears, postauricular areas, and beard area. Men also may have SD on the mid upper chest in association with chest hair. In infants, the scalp and body skin folds often are affected.
Epidemiology
SD affects patients of all ages: infants, adolescents, and adults. It is among the most common dermatologic diagnoses reported in Black patients in the United States.1
Key clinical features in darker skin tones
- In those with darker skin tones, arcuate, polycyclic, or petaloid (flower petallike) plaques may be present (FIGURE A). Also, hypopigmented patches and plaques may be prominent (FIGURES B AND C). The classic description includes thin pink patches and plaques with white greasy scale on the face (FIGURE D).
- The scalp may have diffuse scale or isolated scaly plaques.
Worth noting
- In those with tightly coiled hair, there is a predisposition for dry hair and increased risk for breakage.
- Treatment plans for patients with SD often include frequent hair washing. However, in those with tightly coiled hair, the treatment plan may need to be modified due to hair texture, tendency for dryness, and washing frequency preferences. Washing the scalp at least every 1 to 2 weeks may be a preferred approach for those with tightly coiled hair at increased risk for dryness/breakage vs washing daily.2 In a sample of 201 caregivers of Black girls, Rucker Wright et al3 found that washing the hair more than once per week was not correlated with a lower prevalence of SD.
- If tightly coiled hair is temporarily straightened with heat (eg, blow-dryer, flat iron), adding a liquid-based treatment such as clobetasol solution or fluocinonide solution will cause the hair to revert to its normal curl pattern.
- It is appropriate to ask patients for their vehicle preference for medications.2 For example, if clobetasol is the treatment selected for the patient, the vehicle can reflect patient preference for a liquid, foam, cream, or ointment.
- Some antifungal/antiyeast shampoos may cause further hair dryness and breakage.
- Treatment may be delayed because patients often use various topical pomades and ointments to cover up the scale and help with pruritus.
- Diffuse scale of tinea capitis in school- aged children can be mistaken for SD, which leads to delayed diagnosis and treatment.
- Clinicians should become comfortable with scalp examinations in patients with tightly coiled hair. Patients with chief concerns related to their hair and scalp expect their clinicians to touch these areas. Avoid leaning in to examine the patient without touching the patient’s hair and scalp.2,4
Health disparity highlight
SD is among the most common cutaneous disorders diagnosed in patients with skin of color.1,5 Delay in recognition of SD in those with darker skin tones leads to delayed treatment. SD of the face can cause notable postinflammatory pigmentation alteration. Pigmentation changes in the skin further impact quality of life.
1. Alexis AF, Sergay AB, Taylor SC. Common dermatologic disorders in skin of color: a comparative practice survey. Cutis. 2007;80:387-394.
2. Grayson C, Heath C. Tips for addressing common conditions affecting pediatric and adolescent patients with skin of color [published online March 2, 2021]. Pediatr Dermatol. 2021;10.1111/ pde.14525
3. Rucker Wright D, Gathers R, Kapke A, et al. Hair care practices and their association with scalp and hair disorders in African American girls. J Am Acad Dermatol. 2011;64: 253-262. doi:10.1016/j.jaad.2010.05.037
4. Grayson C, Heath C. An approach to examining tightly coiled hair among patients with hair loss in race-discordant patientphysician interactions. JAMA Dermatol. 2021;157:505-506. doi:10.1001/jamadermatol.2021.0338
5. Gaulding JV, Gutierrez D, Bhatia BK, et al. Epidemiology of skin diseases in a diverse patient population. J Drugs Dermatol. 2018;17:1032-1036.
1. Alexis AF, Sergay AB, Taylor SC. Common dermatologic disorders in skin of color: a comparative practice survey. Cutis. 2007;80:387-394.
2. Grayson C, Heath C. Tips for addressing common conditions affecting pediatric and adolescent patients with skin of color [published online March 2, 2021]. Pediatr Dermatol. 2021;10.1111/ pde.14525
3. Rucker Wright D, Gathers R, Kapke A, et al. Hair care practices and their association with scalp and hair disorders in African American girls. J Am Acad Dermatol. 2011;64: 253-262. doi:10.1016/j.jaad.2010.05.037
4. Grayson C, Heath C. An approach to examining tightly coiled hair among patients with hair loss in race-discordant patientphysician interactions. JAMA Dermatol. 2021;157:505-506. doi:10.1001/jamadermatol.2021.0338
5. Gaulding JV, Gutierrez D, Bhatia BK, et al. Epidemiology of skin diseases in a diverse patient population. J Drugs Dermatol. 2018;17:1032-1036.
Ticagrelor reversal agent achieves quick hemostasis: REVERSE-IT
The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.
“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.
The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.
Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.
REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
Platelet function assays test reversal
On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.
On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.
The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
Hemostasis documented in all but one patient
Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.
Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.
There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.
While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.
The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
No good current options for reversal
Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.
“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.
Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.
“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.
For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”
Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.
Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.
“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.
The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.
Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.
REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
Platelet function assays test reversal
On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.
On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.
The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
Hemostasis documented in all but one patient
Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.
Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.
There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.
While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.
The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
No good current options for reversal
Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.
“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.
Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.
“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.
For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”
Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.
Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.
“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.
The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.
Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.
REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
Platelet function assays test reversal
On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.
On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.
The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
Hemostasis documented in all but one patient
Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.
Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.
There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.
While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.
The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
No good current options for reversal
Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.
“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.
Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.
“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.
For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”
Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.
Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
FROM AHA 2021
Which injections are effective for lateral epicondylitis?
EVIDENCE SUMMARY
Neither corticosteroids nor platelet-rich plasma are superior to placebo
A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.1 In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.2
In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone follow-up. No functional assessments were reported at 6 months.3
The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.4
The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.5
Platelet-rich plasma. A meta-analysis6 of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.
Corticosteroids and PRP. A 2013 3-armed RCT7 (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.
Botulinum toxin shows modest pain improvement, but …
A 2017 meta-analysis8 of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).
Continue to: Prolotherapy needs further study
Prolotherapy needs further study
A 2008 RCT9 of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.
Hyaluronic acid improves pain, but not enough
A 2010 double-blind RCT10 (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.
Autologous blood has no advantage over placebo
The only RCT of autologous blood compared to saline injections11 included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.
Editor’s takeaway
Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Lindenhovius A, Henket M, Gilligan BP, et al. Injection of dexamethasone versus placebo for lateral elbow pain: a prospective, double-blind, randomized clinical trial. J Hand Surg Am. 2008;33:909-919. doi: 10.1016/j.jhsa.2008.02.004
3. Newcomer KL, Laskowski ER, Idank DM, et al. Corticosteroid injection in early treatment of lateral epicondylitis. Clin J Sport Med. 2001;11:214-222. doi: 10.1097/00042752-200110000-00002
4. Coombes BK, Bisset L, Brooks P, et al. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013;309:461-469. doi: 10.1001/jama.2013.129
5. Altay T, Gunal I, Ozturk H. Local injection treatment for lateral epicondylitis. Clin Orthop Relat Res. 2002;398:127-130.
6. Simental-Mendía M, Vilchez-Cavazos F, Álvarez-Villalobos N, et al. Clinical efficacy of platelet-rich plasma in the treatment of lateral epicondylitis: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Clin Rheumatol. 2020;39:2255-2265. doi: 10.1007/s10067-020-05000-y
7. Krogh T, Fredberg U, Stengaard-Pedersen K, et al. Treatment of lateral epicondylitis with platelet-rich-plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2013;41:625-635. doi:10.1177/0363546512472975
8. Lin Y, Wu W, Hsu Y, et al. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis. Clin Rehabil. 2017;32:131-145. doi:10.1177/0269215517702517
9. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sports Med. 2008;18:248-254. doi: 10.1097/JSM.0b013e318170fc87
10. Petrella R, Cogliano A, Decaria J, et al. Management of tennis elbow with sodium hyaluronate periarticular injections. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:4. doi: 10.1186/1758-2555-2-4
11. Wolf JM, Ozer K, Scott F, et al. Comparison of autologous blood, corticosteroid, and saline injection in the treatment of lateral epicondylitis: a prospective, randomized, controlled multicenter study. J Hand Surg Am. 2011;36:1269-1272. doi: 10.1016/j.jhsa.2011.05.014
EVIDENCE SUMMARY
Neither corticosteroids nor platelet-rich plasma are superior to placebo
A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.1 In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.2
In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone follow-up. No functional assessments were reported at 6 months.3
The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.4
The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.5
Platelet-rich plasma. A meta-analysis6 of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.
Corticosteroids and PRP. A 2013 3-armed RCT7 (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.
Botulinum toxin shows modest pain improvement, but …
A 2017 meta-analysis8 of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).
Continue to: Prolotherapy needs further study
Prolotherapy needs further study
A 2008 RCT9 of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.
Hyaluronic acid improves pain, but not enough
A 2010 double-blind RCT10 (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.
Autologous blood has no advantage over placebo
The only RCT of autologous blood compared to saline injections11 included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.
Editor’s takeaway
Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.
EVIDENCE SUMMARY
Neither corticosteroids nor platelet-rich plasma are superior to placebo
A 2014 systematic review of RCTs of nonsurgical treatments for lateral epicondylitis identified 4 studies comparing corticosteroid injections to saline or anesthetic injections.1 In the first study, investigators followed 64 patients for 6 months. Both groups significantly improved from baseline, but there were no differences in pain or function at 1 or 6 months. Skin discoloration occurred in 2 patients who received lidocaine injection and 1 who received dexamethasone.2
In a second RCT of patients with symptoms for > 4 weeks, 39 participants were randomized to either betamethasone/bupivacaine or bupivacaine-only injections. In-person follow-up occurred at 4 and 8 weeks and telephone follow-up at 6 months. Both groups statistically improved from baseline to 6 months. No differences were seen between groups in pain or functional improvement at 4, 8, or 26 weeks, but the betamethasone group showed statistically greater improvement on the Visual Analog Scale (VAS) from 8 weeks to the final 6-month telephone follow-up. No functional assessments were reported at 6 months.3
The third RCT of 165 patients with lateral epicondylitis for > 6 weeks evaluated 4 intervention groups: corticosteroid injection with/without physiotherapy and placebo (small-volume saline) injection with/without physiotherapy. At the end of 1 year, the corticosteroid injection groups had less complete recovery (83% vs 96%; relative risk [RR] = 0.86; 99% CI, 0.75-0.99) and more recurrences (54% vs 12%; RR = 0.23; 99% CI, 0.10-0.51) than the placebo groups.4
The fourth RCT randomized 120 patients to either 2 mL lidocaine or 1 mL lidocaine plus 1 mL of triamcinolone. At 1-year follow-up, 57 of 60 lidocaine-injected patients had an excellent recovery and 56 of 60 triamcinolone plus lidocaine patients had an excellent recovery.5
Platelet-rich plasma. A meta-analysis6 of RCTs of PRP vs saline injections included 5 trials and 276 patients with a mean age of 48 years; duration of follow-up was 2 to 12 months. No significant differences were found between the groups for pain score—measured by VAS or the Patient-Rated Tennis Elbow Evaluation (PRTEE)—(standardized mean difference [SMD] = –0.51; 95% CI, –1.32 to –0.30) nor for functional score (SMD = 0.07; 95% CI, –0.46 to 0.33). Two of the trials reported adverse reactions of pain around the injection site: 16% to 20% in the PRP group vs 8% to 15% in the saline group.
Corticosteroids and PRP. A 2013 3-armed RCT7 (n = 60) compared 1-time injections of PRP, corticosteroid, and saline for treatment of lateral epicondylitis. Pain was evaluated at 1 and 3 months using the PRTEE. Compared to saline, corticosteroid showed a statistically significant, but not a minimum clinically important, reduction (8% greater improvement) at 1 month but not at 3 months. PRP pain reduction at both 1 and 3 months was not significantly different from placebo. Importantly, a small sample size combined with a high dropout rate (> 70%) limit validity of this study.
Botulinum toxin shows modest pain improvement, but …
A 2017 meta-analysis8 of 4 RCTs (n = 278) compared the effectiveness of botulinum toxin vs saline injection and other nonsurgical treatments for lateral epicondylitis. The studies compared the mean differences in pain relief and hand grip strength in adult patients with lateral epicondylitis symptoms for at least 3 months. Compared with saline injection, botulinum toxin injection significantly reduced pain to a small or medium SMD, at 2 to 4 weeks post injection (SMD = –0.73; 95% CI, –1.29 to –0.17); 8 to 12 weeks post injection (SMD = –0.45; 95% CI, –0.74 to –0.15); and 16+ weeks post injection (SMD = –0.54; 95% CI, –0.98 to –0.11). Harm from botulinum toxin was greater than from saline or corticosteroid, with a significant reduction in grip strength at 2 to 4 weeks (SMD = –0.33; 95% CI, –0.59 to –0.08).
Continue to: Prolotherapy needs further study
Prolotherapy needs further study
A 2008 RCT9 of 20 adults with at least 6 months of lateral epicondylitis received either prolotherapy (1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% bupivacaine HCl, and 3.5 parts normal saline) injections or 0.9% saline injections at baseline, 4 weeks, and 8 weeks. On a 10-point Likert scale, the prolotherapy group had a lower mean pain score at 16 weeks than the saline injection group (0.5 vs 3.5), but not at 8 weeks (3.3 vs 3.6). This pilot study’s results are limited by its small sample size.
Hyaluronic acid improves pain, but not enough
A 2010 double-blind RCT10 (n = 331) compared hyaluronic acid injection vs saline injection in treatment of lateral epicondylitis in adults with > 3 months of symptoms. Two injections were performed 1 week apart, with follow-up at 30 days and at 1 year after the first injection. VAS score in the hyaluronic acid group, at rest and after grip testing, was significantly different (statistically) than in the placebo group but did not meet criteria for minimum clinically important improvement. Review of the literature showed limited follow-up studies on hyaluronic acid for lateral epicondylitis to confirm this RCT.
Autologous blood has no advantage over placebo
The only RCT of autologous blood compared to saline injections11 included patients with lateral epicondylitis for < 6 months: 10 saline injections vs 9 autologous blood injections. Patient scores on the Disabilities of the Arm, Shoulder, and Hand scale (which measures symptoms from 0 to 100; lower is better) showed no difference but favored the saline injections at 2-month (28 vs 20) and 6-month (20 vs 10) follow-up.
Editor’s takeaway
Limiting the evidence review to studies with a placebo comparator clarifies the lack of effectiveness of lateral epicondylitis injections. Neither corticosteroid, platelet-rich plasma, botulinum toxin, prolotherapy, hyaluronic acid, or autologous blood injections have proven superior to saline or anesthetic injections. However, all injections that contained “placebo” significantly improved lateralepicondylitis.
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Lindenhovius A, Henket M, Gilligan BP, et al. Injection of dexamethasone versus placebo for lateral elbow pain: a prospective, double-blind, randomized clinical trial. J Hand Surg Am. 2008;33:909-919. doi: 10.1016/j.jhsa.2008.02.004
3. Newcomer KL, Laskowski ER, Idank DM, et al. Corticosteroid injection in early treatment of lateral epicondylitis. Clin J Sport Med. 2001;11:214-222. doi: 10.1097/00042752-200110000-00002
4. Coombes BK, Bisset L, Brooks P, et al. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013;309:461-469. doi: 10.1001/jama.2013.129
5. Altay T, Gunal I, Ozturk H. Local injection treatment for lateral epicondylitis. Clin Orthop Relat Res. 2002;398:127-130.
6. Simental-Mendía M, Vilchez-Cavazos F, Álvarez-Villalobos N, et al. Clinical efficacy of platelet-rich plasma in the treatment of lateral epicondylitis: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Clin Rheumatol. 2020;39:2255-2265. doi: 10.1007/s10067-020-05000-y
7. Krogh T, Fredberg U, Stengaard-Pedersen K, et al. Treatment of lateral epicondylitis with platelet-rich-plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2013;41:625-635. doi:10.1177/0363546512472975
8. Lin Y, Wu W, Hsu Y, et al. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis. Clin Rehabil. 2017;32:131-145. doi:10.1177/0269215517702517
9. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sports Med. 2008;18:248-254. doi: 10.1097/JSM.0b013e318170fc87
10. Petrella R, Cogliano A, Decaria J, et al. Management of tennis elbow with sodium hyaluronate periarticular injections. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:4. doi: 10.1186/1758-2555-2-4
11. Wolf JM, Ozer K, Scott F, et al. Comparison of autologous blood, corticosteroid, and saline injection in the treatment of lateral epicondylitis: a prospective, randomized, controlled multicenter study. J Hand Surg Am. 2011;36:1269-1272. doi: 10.1016/j.jhsa.2011.05.014
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Lindenhovius A, Henket M, Gilligan BP, et al. Injection of dexamethasone versus placebo for lateral elbow pain: a prospective, double-blind, randomized clinical trial. J Hand Surg Am. 2008;33:909-919. doi: 10.1016/j.jhsa.2008.02.004
3. Newcomer KL, Laskowski ER, Idank DM, et al. Corticosteroid injection in early treatment of lateral epicondylitis. Clin J Sport Med. 2001;11:214-222. doi: 10.1097/00042752-200110000-00002
4. Coombes BK, Bisset L, Brooks P, et al. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013;309:461-469. doi: 10.1001/jama.2013.129
5. Altay T, Gunal I, Ozturk H. Local injection treatment for lateral epicondylitis. Clin Orthop Relat Res. 2002;398:127-130.
6. Simental-Mendía M, Vilchez-Cavazos F, Álvarez-Villalobos N, et al. Clinical efficacy of platelet-rich plasma in the treatment of lateral epicondylitis: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Clin Rheumatol. 2020;39:2255-2265. doi: 10.1007/s10067-020-05000-y
7. Krogh T, Fredberg U, Stengaard-Pedersen K, et al. Treatment of lateral epicondylitis with platelet-rich-plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2013;41:625-635. doi:10.1177/0363546512472975
8. Lin Y, Wu W, Hsu Y, et al. Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis. Clin Rehabil. 2017;32:131-145. doi:10.1177/0269215517702517
9. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sports Med. 2008;18:248-254. doi: 10.1097/JSM.0b013e318170fc87
10. Petrella R, Cogliano A, Decaria J, et al. Management of tennis elbow with sodium hyaluronate periarticular injections. Sports Med Arthrosc Rehabil Ther Technol. 2010;2:4. doi: 10.1186/1758-2555-2-4
11. Wolf JM, Ozer K, Scott F, et al. Comparison of autologous blood, corticosteroid, and saline injection in the treatment of lateral epicondylitis: a prospective, randomized, controlled multicenter study. J Hand Surg Am. 2011;36:1269-1272. doi: 10.1016/j.jhsa.2011.05.014
EVIDENCE-BASED ANSWER:
Placebo injections actually improve lateral epicondylitis at high rates. No other injections convincingly improve it better than placebo.
Corticosteroid injection is not superior to saline or anesthetic injection (strength of recommendation [SOR] A, systematic review of randomized controlled trials [RCTs]). Platelet-rich plasma (PRP) injection is not superior to saline injection (SOR A, meta-analysis of RCTs).
Botulinum toxin injection, compared to saline injection, modestly improved pain in lateral epicondylitis, but with short-term grip-strength weakness (SOR A, meta-analysis of RCTs). Prolotherapy injection, compared to saline injection, improved pain at 16-week, but not at 8-week, follow-up (SOR B, one small pilot RCT).
Hyaluronic acid injection, compared to saline injection, resulted in a statistically significant pain reduction (6%) but did not achieve the minimum clinically important difference (SOR B, single RCT). Autologous blood injection, compared to saline injection, did not improve disability ratings (SOR B, one small RCT).
When the evidence suggests that placebo is best
In this issue of JFP, the Clinical Inquiry seeks to answer the question: What are effective injection treatments for lateral epicondylitis? Answering this question proved to be a daunting task for the authors. The difficulty lies in answering this question: effective compared to what?
The injections evaluated in their comprehensive review—corticosteroids, botulinum toxin, hyaluronic acid, platelet-rich plasma,
There are 2 choices for an ideal comparison group. One choice compares the active intervention to an adequate placebo, the other compares it to another treatment that has previously been proven effective. Ideally, the other treatment would be a “gold standard”—that is, the best treatment currently available. Unfortunately, for treatment of lateral epicondylitis, no gold standard has been established.
So, what is an “adequate placebo” for injection therapy? This is a very difficult question. The placebo should probably include putting a needle into the treatment site and injecting a nonactive substance, such as saline solution. This is the comparison group Vukelic et al chose for their review. But even saline could theoretically be therapeutic.
Another fair comparison for the treatment of lateral epicondylitis would be an injection near, but not at, the lateral epicondyle. Yet another comparison—dry needling without any medication to the lateral epicondyle vs dry needling of an adjacent location—would also be a fair comparison to help understand the effect of needling alone. Unfortunately, these comparisons have not been explored in randomized controlled trials. Although several studies have evaluated dry needling for lateral epicondylitis,2-4 none have used a fair comparison.
Some studies1 evaluating treatments for lateral epicondylitis used comparisons to agents that are ineffective or of uncertain effectiveness. Comparing 1 agent to another ineffective or potentially harmful agent obscures our knowledge. Evidence-based medicine must be built on a reliable foundation.
Vukelic and colleagues did an admirable job of selecting studies with an appropriate comparison group—that is, saline injection, the best comparator that has been studied. What they discovered is that no type of injection therapy has been proven to be better than a saline injection.
So, if your patient is not satisfied with conservative therapy for epicondylitis and wants an injection, salt water seems as good as anything.
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Uygur E, Aktas B, Ozkut A, et al. Dry needling in lateral epicondylitis: a prospective controlled study. Int Orthop. 2017; 41:2321-2325. doi: 10.1007/s00264-017-3604-1
3. Krey D, Borchers J, McCamey K. Tendon needling for treatment of tendinopathy: A systematic review. Phys Sportsmed. 2015;43:80-86. doi: 10.1080/00913847.2015.1004296
4. Jayaseelan DJ, Faller BT, Avery MH. The utilization and effects of filiform dry needling in the management of tendinopathy: a systematic review. Physiother Theory Pract. Published online April 27, 2021. doi: 10.1080/09593985.2021.1920076
In this issue of JFP, the Clinical Inquiry seeks to answer the question: What are effective injection treatments for lateral epicondylitis? Answering this question proved to be a daunting task for the authors. The difficulty lies in answering this question: effective compared to what?
The injections evaluated in their comprehensive review—corticosteroids, botulinum toxin, hyaluronic acid, platelet-rich plasma,
There are 2 choices for an ideal comparison group. One choice compares the active intervention to an adequate placebo, the other compares it to another treatment that has previously been proven effective. Ideally, the other treatment would be a “gold standard”—that is, the best treatment currently available. Unfortunately, for treatment of lateral epicondylitis, no gold standard has been established.
So, what is an “adequate placebo” for injection therapy? This is a very difficult question. The placebo should probably include putting a needle into the treatment site and injecting a nonactive substance, such as saline solution. This is the comparison group Vukelic et al chose for their review. But even saline could theoretically be therapeutic.
Another fair comparison for the treatment of lateral epicondylitis would be an injection near, but not at, the lateral epicondyle. Yet another comparison—dry needling without any medication to the lateral epicondyle vs dry needling of an adjacent location—would also be a fair comparison to help understand the effect of needling alone. Unfortunately, these comparisons have not been explored in randomized controlled trials. Although several studies have evaluated dry needling for lateral epicondylitis,2-4 none have used a fair comparison.
Some studies1 evaluating treatments for lateral epicondylitis used comparisons to agents that are ineffective or of uncertain effectiveness. Comparing 1 agent to another ineffective or potentially harmful agent obscures our knowledge. Evidence-based medicine must be built on a reliable foundation.
Vukelic and colleagues did an admirable job of selecting studies with an appropriate comparison group—that is, saline injection, the best comparator that has been studied. What they discovered is that no type of injection therapy has been proven to be better than a saline injection.
So, if your patient is not satisfied with conservative therapy for epicondylitis and wants an injection, salt water seems as good as anything.
In this issue of JFP, the Clinical Inquiry seeks to answer the question: What are effective injection treatments for lateral epicondylitis? Answering this question proved to be a daunting task for the authors. The difficulty lies in answering this question: effective compared to what?
The injections evaluated in their comprehensive review—corticosteroids, botulinum toxin, hyaluronic acid, platelet-rich plasma,
There are 2 choices for an ideal comparison group. One choice compares the active intervention to an adequate placebo, the other compares it to another treatment that has previously been proven effective. Ideally, the other treatment would be a “gold standard”—that is, the best treatment currently available. Unfortunately, for treatment of lateral epicondylitis, no gold standard has been established.
So, what is an “adequate placebo” for injection therapy? This is a very difficult question. The placebo should probably include putting a needle into the treatment site and injecting a nonactive substance, such as saline solution. This is the comparison group Vukelic et al chose for their review. But even saline could theoretically be therapeutic.
Another fair comparison for the treatment of lateral epicondylitis would be an injection near, but not at, the lateral epicondyle. Yet another comparison—dry needling without any medication to the lateral epicondyle vs dry needling of an adjacent location—would also be a fair comparison to help understand the effect of needling alone. Unfortunately, these comparisons have not been explored in randomized controlled trials. Although several studies have evaluated dry needling for lateral epicondylitis,2-4 none have used a fair comparison.
Some studies1 evaluating treatments for lateral epicondylitis used comparisons to agents that are ineffective or of uncertain effectiveness. Comparing 1 agent to another ineffective or potentially harmful agent obscures our knowledge. Evidence-based medicine must be built on a reliable foundation.
Vukelic and colleagues did an admirable job of selecting studies with an appropriate comparison group—that is, saline injection, the best comparator that has been studied. What they discovered is that no type of injection therapy has been proven to be better than a saline injection.
So, if your patient is not satisfied with conservative therapy for epicondylitis and wants an injection, salt water seems as good as anything.
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Uygur E, Aktas B, Ozkut A, et al. Dry needling in lateral epicondylitis: a prospective controlled study. Int Orthop. 2017; 41:2321-2325. doi: 10.1007/s00264-017-3604-1
3. Krey D, Borchers J, McCamey K. Tendon needling for treatment of tendinopathy: A systematic review. Phys Sportsmed. 2015;43:80-86. doi: 10.1080/00913847.2015.1004296
4. Jayaseelan DJ, Faller BT, Avery MH. The utilization and effects of filiform dry needling in the management of tendinopathy: a systematic review. Physiother Theory Pract. Published online April 27, 2021. doi: 10.1080/09593985.2021.1920076
1. Sims S, Miller K, Elfar J, et al. Non-surgical treatment of lateral epicondylitis: a systematic review of randomized controlled trials. Hand (NY). 2014;9:419-446. doi: 10.1007/s11552-014-9642-x
2. Uygur E, Aktas B, Ozkut A, et al. Dry needling in lateral epicondylitis: a prospective controlled study. Int Orthop. 2017; 41:2321-2325. doi: 10.1007/s00264-017-3604-1
3. Krey D, Borchers J, McCamey K. Tendon needling for treatment of tendinopathy: A systematic review. Phys Sportsmed. 2015;43:80-86. doi: 10.1080/00913847.2015.1004296
4. Jayaseelan DJ, Faller BT, Avery MH. The utilization and effects of filiform dry needling in the management of tendinopathy: a systematic review. Physiother Theory Pract. Published online April 27, 2021. doi: 10.1080/09593985.2021.1920076
Successful accelerated taper for sleeping aid
THE CASE
A 49-year-old man with chronic insomnia was referred to the pharmacist authors (LF and DP) to initiate and manage the tapering of nightly zolpidem use. Per chart review, the patient had complaints of insomnia for more than 30 years. His care had been transferred to a Nebraska clinic 5 years earlier, with a medication list that included zolpidem controlled release (CR) 12.5 mg nightly. Since then, multiple interventions to achieve cessation had been tried, including counseling on sleep hygiene, adjunct antidepressant use, and abrupt discontinuation. Each of these methods was unsuccessful. So, his family physician (SS) reached out to the pharmacist authors (LF and DP).
THE APPROACH
Due to the patient’s long history of zolpidem use, a lack of literature on the topic, and worry for withdrawal symptoms, a taper schedule was designed utilizing various benzodiazepine taper resources for guidance. The proposed taper utilized 5-mg immediate release (IR) tablets to ensure ease of tapering. The taper ranged from 20% to 43% weekly reductions based on the ability to split the zolpidem tablet in half.
DISCUSSION
Zolpidem is a sedative-hypnotic medication indicated for the treatment of insomnia when used at therapeutic dosing (ie, 5 to 10 mg nightly). Anecdotal efficacy, accompanied by weak chronic insomnia guideline recommendations, has led prescribers to use zolpidem as a chronic medication to treat insomnia.1,2 There is evidence of dependence and possible seizures from supratherapeutic zolpidem doses in the hundreds of milligrams, raising safety concerns regarding abuse, dependence, and withdrawal seizures in chronic use.2,3
Additionally, there is limited evidence regarding the appropriate process of discontinuing zolpidem after chronic use.2 Often a taper schedule—similar to those used with benzodiazepine medications—is used as a reference for discontinuation.1 The hypothetical goal of a taper is to prevent withdrawal effects such as rebound insomnia, anxiety, palpitations, and seizures.3 However, an extended taper may not actually be necessary with chronic zolpidem patients.
Tapering with minimal adverse effects
Pharmacokinetic and pharmacodynamic studies have suggested minimal, if not complete, absence of rebound or withdrawal effects with short-term zolpidem use.4 The same appears to be true of patients with long-term use. In a study, Roehrs and colleagues5 explored whether long-term treatment (defined as 8 months) caused rebound insomnia upon abrupt withdrawal. The investigators concluded that people with primary insomnia do not experience rebound insomnia or withdrawal symptoms with chronic, therapeutic dosing.
Another study involving 92 elderly patients on long-term treatment of zolpidem (defined as > 1 month, with average around 9.9 ± 6.2 years) experienced only 1 or 2 nights of rebound insomnia during a month-long taper.1,6 Following that, they experienced improvements in initiation and staying asleep.
A possible explanation for the lack of dependence or withdrawal symptoms in patients chronically treated with zolpidem is the pharmacokinetic profile. While the selectivity of the binding sites differentiates this medication from benzodiazepines, the additional fact of a short half-life, and no repeated dosing throughout the day, likely limit the risk of experiencing withdrawal symptoms.1 The daily periods of minimal zolpidem exposure in the body may limit the amount of physical dependence.
Continue to: Discontinuation of zolpidem
Discontinuation of zolpidem
The 49-year-old man had a history of failed abrupt discontinuation of zolpidem in the past (without noted withdrawal symptoms). Thus, various benzodiazepine taper resources were consulted to develop a taper schedule.
We switched our patient from the zolpidem CR 12.5 mg nightly to 10 mg of the IR formulation, and the pharmacists proposed 20% to 43% weekly decreases in dosing based on dosage strengths. At the initial 3-day follow-up (having taken 10 mg nightly for 3 days), the patient reported a quicker onset of sleep but an inability to sleep through the night. The patient denied withdrawal symptoms or any significant impact to his daily routines. These results encouraged a progression to the next step of the taper. For the next 9 days, the patient took 5 mg nightly, rather than the pharmacist-advised dosing of alternating 5 mg and 10 mg nightly, and reported similar outcomes at his next visit.
This success led to the discontinuation of scheduled zolpidem. The patient was also given a prescription of 2.5 mg, as needed, if insomnia rebounded. No adverse effects were noted despite the accelerated taper. Based on patient response and motivation, the taper had progressed more quickly than scheduled, resulting in 3 days of 10 mg, 9 days of 5 mg, and 1 final day of 2.5 mg that was used when the patient had trouble falling asleep. At the 6-month follow-up, the patient informed the physician that he had neither experienced insomnia nor used any further medication.
THE TAKEAWAY
This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use. Although withdrawal is often patient specific, this case suggests the risk is low despite the chronic usage. This further adds to the literature suggesting against the need for an extended taper, and possibly a taper at all, when using recommended doses of chronic zolpidem. This is a significant difference compared to past practices that drew from literature-based benzodiazepine tapers.6 This case serves as an observational point of reference for clinicians who are assisting patients with chronic zolpidem tapers.
CORRESPONDENCE
Logan Franck, PharmD, 986145 Nebraska Medical Center, Omaha, NE 68198-6145; logan.franck@unmc.edu
1. Lähteenmäki R, Neuvonen PJ, Puustinen J, et al. Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia. Basic Clin Pharmacol Toxicol. 2019;124:330-340. doi: 10.1111/bcpt.13144
2. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13:307-349. doi: 10.5664/jcsm.6470
3. Haji Seyed Javadi SA, Hajiali F, Nassiri-Asl M. Zolpidem dependency and withdrawal seizure: a case report study. Iran Red Crescent Med J. 2014;16:e19926. doi: 10.5812/ircmj.19926
4. Salvà P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet. 1995;29:142-153. doi: 10.2165/00003088-199529030-00002
5. Roehrs TA, Randall S, Harris E, et al. Twelve months of nightly zolpidem does not lead to rebound insomnia or withdrawal symptoms: a prospective placebo-controlled study. J Psychopharmacol. 2012;26:1088-1095. doi: 10.1177/0269881111424455
6. Lader M. Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol 2014;77:295-301. doi: 10.1111/j.1365-2125.2012.04418.x
THE CASE
A 49-year-old man with chronic insomnia was referred to the pharmacist authors (LF and DP) to initiate and manage the tapering of nightly zolpidem use. Per chart review, the patient had complaints of insomnia for more than 30 years. His care had been transferred to a Nebraska clinic 5 years earlier, with a medication list that included zolpidem controlled release (CR) 12.5 mg nightly. Since then, multiple interventions to achieve cessation had been tried, including counseling on sleep hygiene, adjunct antidepressant use, and abrupt discontinuation. Each of these methods was unsuccessful. So, his family physician (SS) reached out to the pharmacist authors (LF and DP).
THE APPROACH
Due to the patient’s long history of zolpidem use, a lack of literature on the topic, and worry for withdrawal symptoms, a taper schedule was designed utilizing various benzodiazepine taper resources for guidance. The proposed taper utilized 5-mg immediate release (IR) tablets to ensure ease of tapering. The taper ranged from 20% to 43% weekly reductions based on the ability to split the zolpidem tablet in half.
DISCUSSION
Zolpidem is a sedative-hypnotic medication indicated for the treatment of insomnia when used at therapeutic dosing (ie, 5 to 10 mg nightly). Anecdotal efficacy, accompanied by weak chronic insomnia guideline recommendations, has led prescribers to use zolpidem as a chronic medication to treat insomnia.1,2 There is evidence of dependence and possible seizures from supratherapeutic zolpidem doses in the hundreds of milligrams, raising safety concerns regarding abuse, dependence, and withdrawal seizures in chronic use.2,3
Additionally, there is limited evidence regarding the appropriate process of discontinuing zolpidem after chronic use.2 Often a taper schedule—similar to those used with benzodiazepine medications—is used as a reference for discontinuation.1 The hypothetical goal of a taper is to prevent withdrawal effects such as rebound insomnia, anxiety, palpitations, and seizures.3 However, an extended taper may not actually be necessary with chronic zolpidem patients.
Tapering with minimal adverse effects
Pharmacokinetic and pharmacodynamic studies have suggested minimal, if not complete, absence of rebound or withdrawal effects with short-term zolpidem use.4 The same appears to be true of patients with long-term use. In a study, Roehrs and colleagues5 explored whether long-term treatment (defined as 8 months) caused rebound insomnia upon abrupt withdrawal. The investigators concluded that people with primary insomnia do not experience rebound insomnia or withdrawal symptoms with chronic, therapeutic dosing.
Another study involving 92 elderly patients on long-term treatment of zolpidem (defined as > 1 month, with average around 9.9 ± 6.2 years) experienced only 1 or 2 nights of rebound insomnia during a month-long taper.1,6 Following that, they experienced improvements in initiation and staying asleep.
A possible explanation for the lack of dependence or withdrawal symptoms in patients chronically treated with zolpidem is the pharmacokinetic profile. While the selectivity of the binding sites differentiates this medication from benzodiazepines, the additional fact of a short half-life, and no repeated dosing throughout the day, likely limit the risk of experiencing withdrawal symptoms.1 The daily periods of minimal zolpidem exposure in the body may limit the amount of physical dependence.
Continue to: Discontinuation of zolpidem
Discontinuation of zolpidem
The 49-year-old man had a history of failed abrupt discontinuation of zolpidem in the past (without noted withdrawal symptoms). Thus, various benzodiazepine taper resources were consulted to develop a taper schedule.
We switched our patient from the zolpidem CR 12.5 mg nightly to 10 mg of the IR formulation, and the pharmacists proposed 20% to 43% weekly decreases in dosing based on dosage strengths. At the initial 3-day follow-up (having taken 10 mg nightly for 3 days), the patient reported a quicker onset of sleep but an inability to sleep through the night. The patient denied withdrawal symptoms or any significant impact to his daily routines. These results encouraged a progression to the next step of the taper. For the next 9 days, the patient took 5 mg nightly, rather than the pharmacist-advised dosing of alternating 5 mg and 10 mg nightly, and reported similar outcomes at his next visit.
This success led to the discontinuation of scheduled zolpidem. The patient was also given a prescription of 2.5 mg, as needed, if insomnia rebounded. No adverse effects were noted despite the accelerated taper. Based on patient response and motivation, the taper had progressed more quickly than scheduled, resulting in 3 days of 10 mg, 9 days of 5 mg, and 1 final day of 2.5 mg that was used when the patient had trouble falling asleep. At the 6-month follow-up, the patient informed the physician that he had neither experienced insomnia nor used any further medication.
THE TAKEAWAY
This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use. Although withdrawal is often patient specific, this case suggests the risk is low despite the chronic usage. This further adds to the literature suggesting against the need for an extended taper, and possibly a taper at all, when using recommended doses of chronic zolpidem. This is a significant difference compared to past practices that drew from literature-based benzodiazepine tapers.6 This case serves as an observational point of reference for clinicians who are assisting patients with chronic zolpidem tapers.
CORRESPONDENCE
Logan Franck, PharmD, 986145 Nebraska Medical Center, Omaha, NE 68198-6145; logan.franck@unmc.edu
THE CASE
A 49-year-old man with chronic insomnia was referred to the pharmacist authors (LF and DP) to initiate and manage the tapering of nightly zolpidem use. Per chart review, the patient had complaints of insomnia for more than 30 years. His care had been transferred to a Nebraska clinic 5 years earlier, with a medication list that included zolpidem controlled release (CR) 12.5 mg nightly. Since then, multiple interventions to achieve cessation had been tried, including counseling on sleep hygiene, adjunct antidepressant use, and abrupt discontinuation. Each of these methods was unsuccessful. So, his family physician (SS) reached out to the pharmacist authors (LF and DP).
THE APPROACH
Due to the patient’s long history of zolpidem use, a lack of literature on the topic, and worry for withdrawal symptoms, a taper schedule was designed utilizing various benzodiazepine taper resources for guidance. The proposed taper utilized 5-mg immediate release (IR) tablets to ensure ease of tapering. The taper ranged from 20% to 43% weekly reductions based on the ability to split the zolpidem tablet in half.
DISCUSSION
Zolpidem is a sedative-hypnotic medication indicated for the treatment of insomnia when used at therapeutic dosing (ie, 5 to 10 mg nightly). Anecdotal efficacy, accompanied by weak chronic insomnia guideline recommendations, has led prescribers to use zolpidem as a chronic medication to treat insomnia.1,2 There is evidence of dependence and possible seizures from supratherapeutic zolpidem doses in the hundreds of milligrams, raising safety concerns regarding abuse, dependence, and withdrawal seizures in chronic use.2,3
Additionally, there is limited evidence regarding the appropriate process of discontinuing zolpidem after chronic use.2 Often a taper schedule—similar to those used with benzodiazepine medications—is used as a reference for discontinuation.1 The hypothetical goal of a taper is to prevent withdrawal effects such as rebound insomnia, anxiety, palpitations, and seizures.3 However, an extended taper may not actually be necessary with chronic zolpidem patients.
Tapering with minimal adverse effects
Pharmacokinetic and pharmacodynamic studies have suggested minimal, if not complete, absence of rebound or withdrawal effects with short-term zolpidem use.4 The same appears to be true of patients with long-term use. In a study, Roehrs and colleagues5 explored whether long-term treatment (defined as 8 months) caused rebound insomnia upon abrupt withdrawal. The investigators concluded that people with primary insomnia do not experience rebound insomnia or withdrawal symptoms with chronic, therapeutic dosing.
Another study involving 92 elderly patients on long-term treatment of zolpidem (defined as > 1 month, with average around 9.9 ± 6.2 years) experienced only 1 or 2 nights of rebound insomnia during a month-long taper.1,6 Following that, they experienced improvements in initiation and staying asleep.
A possible explanation for the lack of dependence or withdrawal symptoms in patients chronically treated with zolpidem is the pharmacokinetic profile. While the selectivity of the binding sites differentiates this medication from benzodiazepines, the additional fact of a short half-life, and no repeated dosing throughout the day, likely limit the risk of experiencing withdrawal symptoms.1 The daily periods of minimal zolpidem exposure in the body may limit the amount of physical dependence.
Continue to: Discontinuation of zolpidem
Discontinuation of zolpidem
The 49-year-old man had a history of failed abrupt discontinuation of zolpidem in the past (without noted withdrawal symptoms). Thus, various benzodiazepine taper resources were consulted to develop a taper schedule.
We switched our patient from the zolpidem CR 12.5 mg nightly to 10 mg of the IR formulation, and the pharmacists proposed 20% to 43% weekly decreases in dosing based on dosage strengths. At the initial 3-day follow-up (having taken 10 mg nightly for 3 days), the patient reported a quicker onset of sleep but an inability to sleep through the night. The patient denied withdrawal symptoms or any significant impact to his daily routines. These results encouraged a progression to the next step of the taper. For the next 9 days, the patient took 5 mg nightly, rather than the pharmacist-advised dosing of alternating 5 mg and 10 mg nightly, and reported similar outcomes at his next visit.
This success led to the discontinuation of scheduled zolpidem. The patient was also given a prescription of 2.5 mg, as needed, if insomnia rebounded. No adverse effects were noted despite the accelerated taper. Based on patient response and motivation, the taper had progressed more quickly than scheduled, resulting in 3 days of 10 mg, 9 days of 5 mg, and 1 final day of 2.5 mg that was used when the patient had trouble falling asleep. At the 6-month follow-up, the patient informed the physician that he had neither experienced insomnia nor used any further medication.
THE TAKEAWAY
This case documents a successfully accelerated taper for a patient with a chronic history (> 5 years) of zolpidem use. Although withdrawal is often patient specific, this case suggests the risk is low despite the chronic usage. This further adds to the literature suggesting against the need for an extended taper, and possibly a taper at all, when using recommended doses of chronic zolpidem. This is a significant difference compared to past practices that drew from literature-based benzodiazepine tapers.6 This case serves as an observational point of reference for clinicians who are assisting patients with chronic zolpidem tapers.
CORRESPONDENCE
Logan Franck, PharmD, 986145 Nebraska Medical Center, Omaha, NE 68198-6145; logan.franck@unmc.edu
1. Lähteenmäki R, Neuvonen PJ, Puustinen J, et al. Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia. Basic Clin Pharmacol Toxicol. 2019;124:330-340. doi: 10.1111/bcpt.13144
2. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13:307-349. doi: 10.5664/jcsm.6470
3. Haji Seyed Javadi SA, Hajiali F, Nassiri-Asl M. Zolpidem dependency and withdrawal seizure: a case report study. Iran Red Crescent Med J. 2014;16:e19926. doi: 10.5812/ircmj.19926
4. Salvà P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet. 1995;29:142-153. doi: 10.2165/00003088-199529030-00002
5. Roehrs TA, Randall S, Harris E, et al. Twelve months of nightly zolpidem does not lead to rebound insomnia or withdrawal symptoms: a prospective placebo-controlled study. J Psychopharmacol. 2012;26:1088-1095. doi: 10.1177/0269881111424455
6. Lader M. Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol 2014;77:295-301. doi: 10.1111/j.1365-2125.2012.04418.x
1. Lähteenmäki R, Neuvonen PJ, Puustinen J, et al. Withdrawal from long-term use of zopiclone, zolpidem and temazepam may improve perceived sleep and quality of life in older adults with primary insomnia. Basic Clin Pharmacol Toxicol. 2019;124:330-340. doi: 10.1111/bcpt.13144
2. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13:307-349. doi: 10.5664/jcsm.6470
3. Haji Seyed Javadi SA, Hajiali F, Nassiri-Asl M. Zolpidem dependency and withdrawal seizure: a case report study. Iran Red Crescent Med J. 2014;16:e19926. doi: 10.5812/ircmj.19926
4. Salvà P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet. 1995;29:142-153. doi: 10.2165/00003088-199529030-00002
5. Roehrs TA, Randall S, Harris E, et al. Twelve months of nightly zolpidem does not lead to rebound insomnia or withdrawal symptoms: a prospective placebo-controlled study. J Psychopharmacol. 2012;26:1088-1095. doi: 10.1177/0269881111424455
6. Lader M. Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol 2014;77:295-301. doi: 10.1111/j.1365-2125.2012.04418.x
