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Video : The SHM Research Committee: Expanding the role and footprint of research in hospital medicine
ORLANDO – In a video interview, Stephanie Mueller, MD, SFHM, of Brigham and Women’s Hospital, Boston, discusses the scope and importance of the SHM Research Committee.
One of its most important roles is overseeing the yearly Scientific Abstract and Poster Competition, known as the Research, Innovations and Clinical Vignettes (RIV) portion of the annual conference, which brings the best of current research in hospital medicine, especially in the increasingly important area of value in patient care, to the members.
In discussing the work of the committee, Dr. Mueller – who is in her third year as a member – adds that they “are working to expand the research footprint within the Society of Hospital Medicine,” including implementing initiatives such as the VIP program, which is a visiting professorship in which junior and mid-level faculty can do an exchange program between institutions.
ORLANDO – In a video interview, Stephanie Mueller, MD, SFHM, of Brigham and Women’s Hospital, Boston, discusses the scope and importance of the SHM Research Committee.
One of its most important roles is overseeing the yearly Scientific Abstract and Poster Competition, known as the Research, Innovations and Clinical Vignettes (RIV) portion of the annual conference, which brings the best of current research in hospital medicine, especially in the increasingly important area of value in patient care, to the members.
In discussing the work of the committee, Dr. Mueller – who is in her third year as a member – adds that they “are working to expand the research footprint within the Society of Hospital Medicine,” including implementing initiatives such as the VIP program, which is a visiting professorship in which junior and mid-level faculty can do an exchange program between institutions.
ORLANDO – In a video interview, Stephanie Mueller, MD, SFHM, of Brigham and Women’s Hospital, Boston, discusses the scope and importance of the SHM Research Committee.
One of its most important roles is overseeing the yearly Scientific Abstract and Poster Competition, known as the Research, Innovations and Clinical Vignettes (RIV) portion of the annual conference, which brings the best of current research in hospital medicine, especially in the increasingly important area of value in patient care, to the members.
In discussing the work of the committee, Dr. Mueller – who is in her third year as a member – adds that they “are working to expand the research footprint within the Society of Hospital Medicine,” including implementing initiatives such as the VIP program, which is a visiting professorship in which junior and mid-level faculty can do an exchange program between institutions.
REPORTING FROM HOSPITAL MEDICINE 2018
FDA orders new restrictions on sale, distribution of Essure
The Food and Drug Administration has restricted the sale and distribution of Bayer’s Essure permanent contraception device to only health care providers and facilities that provide patients with information about the risks and benefits of the device.
In an order issued April 9, the FDA’s Center for Devices and Radiological Health informed Bayer of the restrictions, citing a need to “provide reasonable assurance of the safety and effectiveness of the device.”
Bayer must implement the restrictions immediately and must ensure health care provider compliance.
“The FDA is taking this step after becoming aware that some women were not being adequately informed of Essure’s risks before getting the device implanted, despite previous significant efforts to educate patients and doctors about the risks associated with this device,” the agency said in a press release, adding that it “plans to enforce these requirements and will take appropriate action for a failure to comply, including applicable criminal and civil penalties.”
Essure, which is the only permanently implanted birth control device for women on the market that does not require a surgical incision, was approved in 2002 and has been associated with adverse events including perforation of the uterus and/or fallopian tubes, device migration into the abdomen or pelvis, persistent pain, and suspected allergic reactions or hypersensitivity. Some women have also reported headache, fatigue, weight changes, hair loss, and mood changes.
In 2016, based on product safety monitoring by the FDA, a postmarketing study was ordered, as was a boxed warning and a more comprehensive patient decision checklist to inform patients about the risk of adverse events.
“We’ve been closely evaluating new information on the use of Essure, and based on our review of a growing body of evidence, we believe this product requires additional, meaningful safeguards to ensure women are able to make informed decisions about risk when considering this option,” FDA commissioner Scott Gottlieb, MD, said in the press release, adding that it is unacceptable that some women were not being adequately informed.
“Every single woman receiving this device should fully understand the associated risks,” he said.
Terri Cornelison, MD, assistant director for the health of women in the Center for Devices and Radiological Health added that ensuring informed decision making is just one important step in ongoing efforts to monitor the Essure device.
“We remain committed to carefully and throughly considering all new data and evidence and will continue to work with patients affected by this device as part of our process,” she said. “While some women may continue to choose Essure as their birth control option based on current information, as new information becomes available, the FDA will continue to keep the public informed of the agency’s evaluation and findings and consider regulatory options that appropriately balance benefits and risks for Essure.”
The Food and Drug Administration has restricted the sale and distribution of Bayer’s Essure permanent contraception device to only health care providers and facilities that provide patients with information about the risks and benefits of the device.
In an order issued April 9, the FDA’s Center for Devices and Radiological Health informed Bayer of the restrictions, citing a need to “provide reasonable assurance of the safety and effectiveness of the device.”
Bayer must implement the restrictions immediately and must ensure health care provider compliance.
“The FDA is taking this step after becoming aware that some women were not being adequately informed of Essure’s risks before getting the device implanted, despite previous significant efforts to educate patients and doctors about the risks associated with this device,” the agency said in a press release, adding that it “plans to enforce these requirements and will take appropriate action for a failure to comply, including applicable criminal and civil penalties.”
Essure, which is the only permanently implanted birth control device for women on the market that does not require a surgical incision, was approved in 2002 and has been associated with adverse events including perforation of the uterus and/or fallopian tubes, device migration into the abdomen or pelvis, persistent pain, and suspected allergic reactions or hypersensitivity. Some women have also reported headache, fatigue, weight changes, hair loss, and mood changes.
In 2016, based on product safety monitoring by the FDA, a postmarketing study was ordered, as was a boxed warning and a more comprehensive patient decision checklist to inform patients about the risk of adverse events.
“We’ve been closely evaluating new information on the use of Essure, and based on our review of a growing body of evidence, we believe this product requires additional, meaningful safeguards to ensure women are able to make informed decisions about risk when considering this option,” FDA commissioner Scott Gottlieb, MD, said in the press release, adding that it is unacceptable that some women were not being adequately informed.
“Every single woman receiving this device should fully understand the associated risks,” he said.
Terri Cornelison, MD, assistant director for the health of women in the Center for Devices and Radiological Health added that ensuring informed decision making is just one important step in ongoing efforts to monitor the Essure device.
“We remain committed to carefully and throughly considering all new data and evidence and will continue to work with patients affected by this device as part of our process,” she said. “While some women may continue to choose Essure as their birth control option based on current information, as new information becomes available, the FDA will continue to keep the public informed of the agency’s evaluation and findings and consider regulatory options that appropriately balance benefits and risks for Essure.”
The Food and Drug Administration has restricted the sale and distribution of Bayer’s Essure permanent contraception device to only health care providers and facilities that provide patients with information about the risks and benefits of the device.
In an order issued April 9, the FDA’s Center for Devices and Radiological Health informed Bayer of the restrictions, citing a need to “provide reasonable assurance of the safety and effectiveness of the device.”
Bayer must implement the restrictions immediately and must ensure health care provider compliance.
“The FDA is taking this step after becoming aware that some women were not being adequately informed of Essure’s risks before getting the device implanted, despite previous significant efforts to educate patients and doctors about the risks associated with this device,” the agency said in a press release, adding that it “plans to enforce these requirements and will take appropriate action for a failure to comply, including applicable criminal and civil penalties.”
Essure, which is the only permanently implanted birth control device for women on the market that does not require a surgical incision, was approved in 2002 and has been associated with adverse events including perforation of the uterus and/or fallopian tubes, device migration into the abdomen or pelvis, persistent pain, and suspected allergic reactions or hypersensitivity. Some women have also reported headache, fatigue, weight changes, hair loss, and mood changes.
In 2016, based on product safety monitoring by the FDA, a postmarketing study was ordered, as was a boxed warning and a more comprehensive patient decision checklist to inform patients about the risk of adverse events.
“We’ve been closely evaluating new information on the use of Essure, and based on our review of a growing body of evidence, we believe this product requires additional, meaningful safeguards to ensure women are able to make informed decisions about risk when considering this option,” FDA commissioner Scott Gottlieb, MD, said in the press release, adding that it is unacceptable that some women were not being adequately informed.
“Every single woman receiving this device should fully understand the associated risks,” he said.
Terri Cornelison, MD, assistant director for the health of women in the Center for Devices and Radiological Health added that ensuring informed decision making is just one important step in ongoing efforts to monitor the Essure device.
“We remain committed to carefully and throughly considering all new data and evidence and will continue to work with patients affected by this device as part of our process,” she said. “While some women may continue to choose Essure as their birth control option based on current information, as new information becomes available, the FDA will continue to keep the public informed of the agency’s evaluation and findings and consider regulatory options that appropriately balance benefits and risks for Essure.”
SHM presidents: Innovate and avoid complacency
ORLANDO – In a time of tumult in American health care, hospital medicine can expect to see a reimagined – but not reduced – role, said the outgoing and current presidents of the Society of Hospital Medicine at Monday’s HM18 opening plenary.
Despite the many successes of the relatively young field of hospital medicine, there’s no room for complacency, said SHM’s immediate past president Ron Greeno, MD, MHM.
Dr. Greeno drew on his 25-year career in hospital medicine to frame past successes and upcoming challenges for hospital medicine in the 21st century.
As the profession defined itself and grew from the 1980s onward, “the model was challenged, and challenged significantly, mostly by our physician colleagues,” who either feared or didn’t understand the model, he said. All along, though, pioneers in hospital medicine were just trying “to figure out a way to take better care of patients in the hospital.”
The result, said Dr. Greeno, is that hospital medicine stands unique among physician specialties. “We as a specialty are in a very enviable position as we move into the post–health care reform era. More than any other specialty in the history of medicine, we are not expected to p
“Colleagues honor us by trusting us with their patients’ care … but we need to be aware that they are watching us and judging whether we are living up to our promises,” Dr. Greeno said. “So we need to be asking ourselves some tough questions. Perhaps we’re becoming too self-satisfied. Perhaps we are starting to believe our own press.”
Without an appetite for innovation as well as hard work, hospitalists could risk becoming “highly paid worker bees,” said Dr. Greeno.
“There are people who think this is happening. I know because I have talked to them while traveling around the country” as SHM president, he said. “I am not among that group. I think the best is yet to come … that we will become more integrated and have ever more impact and influence in the redesign of the U.S. health care system.”
More than anything, Dr. Greeno’s faith in the profession’s future is grounded in its human capital. Addressing the plenary attendees, he said, “You come here just to become better, to try to make things better. I see all of you who refuse to let the urgent get in the way of the important.”
In her first address as the new SHM president, Nasim Afsar, MD, SFHM, agreed that the people really do make the profession. “We will prevail because of our perseverance and our passion to be part of the solution for challenges in health care,” she said.
Dr. Afsar is chief ambulatory officer and chief medical officer for ACOs at UC Irvine Health. She said that earlier this year, she’d never felt more sure of her job security. Serving on the inpatient hospitalist service during the height of this year’s surging influenza season, Dr. Afsar saw a packed emergency department and a completely full house for her hospital. “We had to create a new hospitalist service” just to handle the volume, she said.
A sobering experience later that month, though, had her rethinking things. At a meeting of chief executive officers of health care systems, leaders spoke of hospitals transitioning from profit centers to cost centers. Some of the proposed innovations were startling: “When I heard talk of hospitals at home, and of virtual hospitals, I got a very different sense of our specialty,” said Dr. Afsar.
Still, she said, she’s confident there will be jobs for hospitalists in the future. “We can’t ignore the significant, irrefutable fact that has emerged: Value will prevail. And the only way to deliver that is population health management,” meaning the delivery of high value care at fair cost across the entire human lifespan, she said.
This call can be answered in two ways, said Dr. Afsar. “First, we have to define and deliver value for hospitalized patients every single day. Second, we have to look at what population health management means for our specialty.”
“I encourage us not to be confined by our names,” Dr. Afsar said. Rather, hospitalists will be defined by the attributes that they’ve become known for over the years: “Innovators. Problem solvers. Collaborators. Patient advocates.”
ORLANDO – In a time of tumult in American health care, hospital medicine can expect to see a reimagined – but not reduced – role, said the outgoing and current presidents of the Society of Hospital Medicine at Monday’s HM18 opening plenary.
Despite the many successes of the relatively young field of hospital medicine, there’s no room for complacency, said SHM’s immediate past president Ron Greeno, MD, MHM.
Dr. Greeno drew on his 25-year career in hospital medicine to frame past successes and upcoming challenges for hospital medicine in the 21st century.
As the profession defined itself and grew from the 1980s onward, “the model was challenged, and challenged significantly, mostly by our physician colleagues,” who either feared or didn’t understand the model, he said. All along, though, pioneers in hospital medicine were just trying “to figure out a way to take better care of patients in the hospital.”
The result, said Dr. Greeno, is that hospital medicine stands unique among physician specialties. “We as a specialty are in a very enviable position as we move into the post–health care reform era. More than any other specialty in the history of medicine, we are not expected to p
“Colleagues honor us by trusting us with their patients’ care … but we need to be aware that they are watching us and judging whether we are living up to our promises,” Dr. Greeno said. “So we need to be asking ourselves some tough questions. Perhaps we’re becoming too self-satisfied. Perhaps we are starting to believe our own press.”
Without an appetite for innovation as well as hard work, hospitalists could risk becoming “highly paid worker bees,” said Dr. Greeno.
“There are people who think this is happening. I know because I have talked to them while traveling around the country” as SHM president, he said. “I am not among that group. I think the best is yet to come … that we will become more integrated and have ever more impact and influence in the redesign of the U.S. health care system.”
More than anything, Dr. Greeno’s faith in the profession’s future is grounded in its human capital. Addressing the plenary attendees, he said, “You come here just to become better, to try to make things better. I see all of you who refuse to let the urgent get in the way of the important.”
In her first address as the new SHM president, Nasim Afsar, MD, SFHM, agreed that the people really do make the profession. “We will prevail because of our perseverance and our passion to be part of the solution for challenges in health care,” she said.
Dr. Afsar is chief ambulatory officer and chief medical officer for ACOs at UC Irvine Health. She said that earlier this year, she’d never felt more sure of her job security. Serving on the inpatient hospitalist service during the height of this year’s surging influenza season, Dr. Afsar saw a packed emergency department and a completely full house for her hospital. “We had to create a new hospitalist service” just to handle the volume, she said.
A sobering experience later that month, though, had her rethinking things. At a meeting of chief executive officers of health care systems, leaders spoke of hospitals transitioning from profit centers to cost centers. Some of the proposed innovations were startling: “When I heard talk of hospitals at home, and of virtual hospitals, I got a very different sense of our specialty,” said Dr. Afsar.
Still, she said, she’s confident there will be jobs for hospitalists in the future. “We can’t ignore the significant, irrefutable fact that has emerged: Value will prevail. And the only way to deliver that is population health management,” meaning the delivery of high value care at fair cost across the entire human lifespan, she said.
This call can be answered in two ways, said Dr. Afsar. “First, we have to define and deliver value for hospitalized patients every single day. Second, we have to look at what population health management means for our specialty.”
“I encourage us not to be confined by our names,” Dr. Afsar said. Rather, hospitalists will be defined by the attributes that they’ve become known for over the years: “Innovators. Problem solvers. Collaborators. Patient advocates.”
ORLANDO – In a time of tumult in American health care, hospital medicine can expect to see a reimagined – but not reduced – role, said the outgoing and current presidents of the Society of Hospital Medicine at Monday’s HM18 opening plenary.
Despite the many successes of the relatively young field of hospital medicine, there’s no room for complacency, said SHM’s immediate past president Ron Greeno, MD, MHM.
Dr. Greeno drew on his 25-year career in hospital medicine to frame past successes and upcoming challenges for hospital medicine in the 21st century.
As the profession defined itself and grew from the 1980s onward, “the model was challenged, and challenged significantly, mostly by our physician colleagues,” who either feared or didn’t understand the model, he said. All along, though, pioneers in hospital medicine were just trying “to figure out a way to take better care of patients in the hospital.”
The result, said Dr. Greeno, is that hospital medicine stands unique among physician specialties. “We as a specialty are in a very enviable position as we move into the post–health care reform era. More than any other specialty in the history of medicine, we are not expected to p
“Colleagues honor us by trusting us with their patients’ care … but we need to be aware that they are watching us and judging whether we are living up to our promises,” Dr. Greeno said. “So we need to be asking ourselves some tough questions. Perhaps we’re becoming too self-satisfied. Perhaps we are starting to believe our own press.”
Without an appetite for innovation as well as hard work, hospitalists could risk becoming “highly paid worker bees,” said Dr. Greeno.
“There are people who think this is happening. I know because I have talked to them while traveling around the country” as SHM president, he said. “I am not among that group. I think the best is yet to come … that we will become more integrated and have ever more impact and influence in the redesign of the U.S. health care system.”
More than anything, Dr. Greeno’s faith in the profession’s future is grounded in its human capital. Addressing the plenary attendees, he said, “You come here just to become better, to try to make things better. I see all of you who refuse to let the urgent get in the way of the important.”
In her first address as the new SHM president, Nasim Afsar, MD, SFHM, agreed that the people really do make the profession. “We will prevail because of our perseverance and our passion to be part of the solution for challenges in health care,” she said.
Dr. Afsar is chief ambulatory officer and chief medical officer for ACOs at UC Irvine Health. She said that earlier this year, she’d never felt more sure of her job security. Serving on the inpatient hospitalist service during the height of this year’s surging influenza season, Dr. Afsar saw a packed emergency department and a completely full house for her hospital. “We had to create a new hospitalist service” just to handle the volume, she said.
A sobering experience later that month, though, had her rethinking things. At a meeting of chief executive officers of health care systems, leaders spoke of hospitals transitioning from profit centers to cost centers. Some of the proposed innovations were startling: “When I heard talk of hospitals at home, and of virtual hospitals, I got a very different sense of our specialty,” said Dr. Afsar.
Still, she said, she’s confident there will be jobs for hospitalists in the future. “We can’t ignore the significant, irrefutable fact that has emerged: Value will prevail. And the only way to deliver that is population health management,” meaning the delivery of high value care at fair cost across the entire human lifespan, she said.
This call can be answered in two ways, said Dr. Afsar. “First, we have to define and deliver value for hospitalized patients every single day. Second, we have to look at what population health management means for our specialty.”
“I encourage us not to be confined by our names,” Dr. Afsar said. Rather, hospitalists will be defined by the attributes that they’ve become known for over the years: “Innovators. Problem solvers. Collaborators. Patient advocates.”
Can cN0 and pCR limit axillary surgery in some breast cancer patients?
CHICAGO – Patients with clinically node-negative HER2-positive or triple-negative breast cancer (TNBC) who achieve a pathological complete response in the breast after neoadjuvant chemotherapy could benefit from clinical trials to evaluate the option of omitting axillary node surgery in this population, according to a retrospective analysis of more than 22,000 cases in the National Cancer Database reported at the Society of Surgical Oncology Annual Cancer Symposium.
Alison U. Barron, MD, breast surgery oncology fellow at Mayo, presented the results. “In patients with HER2+ breast cancer and TNBC who are clinically node negative (cN0) and achieve a breast pathological complete response, this data supports omitting axillary surgery in clinical trials assessing no surgery after neoadjuvant chemotherapy (NAC),” she said. “In patients who present with clinically positive node [cN1] disease with a breast pathological complete response, surgical staging of the axilla is still recommended.”
“Response rates to NAC have increased,” Dr. Barron said. She cited previous reports that showed response rates ranging from 9%-13% for anthracyclines to 19%-26% with the addition of taxanes, and to 60%-70% with the addition of trastuzumab and pertuzumab in HER2+ disease. “Furthermore, we know that tumor biology affects response rates, with TNBC and HER2+ disease having the highest rates of pathologic complete response,” she said.
“In the current era when we frequently operate on patients, we find no residual cancer in the tissue at the time of surgery,” Dr. Barron said. “The question arises as to whether we can limit surgery in patients with a pathological complete response.” While imaging has limited ability to reliably detect pCR with 100% specificity, she noted that recent trials have shown the potential of tumor-bed biopsy to identify pCR in patients after NAC (Ann Surg. Published online Oct. 23, 2017. doi: 10.1097/SLA.0000000000002573; JAMA Surg. 2017;152(7):665-70).
The National Cancer Database data the Mayo researchers analyzed yielded an overall breast pCR of 29%. “When broken down by tumor subtype, we saw significantly higher rates of breast pCR in patients with HER2+ disease (42%, n = 3,107) and TNBC (35%, n = 2,469), compared with patients with hormone-receptor positive (HR+)/HER2-negative disease (12%, n = 1,020),” she said.
When the analysis looked specifically at patients who were clinically node negative at presentation and had a pCR, the rates of positive lymph nodes at the time of surgery were 1.6% in HER2+ patients and 1.7% in TNBC disease, Dr. Barron said. “If there was residual disease in the breast, the nodal positivity rate was significantly higher, at 18% in HER2+ and 12% in TNBC,” she added. In those who were clinical N1, the breast pCR rates were similar – 41% in HER2+ and 35% in TNBC – but nodal positivity rates were significantly higher, at 13% and 14%, respectively.
The HR+/HER2- group had significantly lower rates of pCR: 12% in the cN0 and 13% in the cN1 subgroups. This subgroup also had higher nodal positivity rates – in the cN0 subgroup, 4% in those with a breast pCR and 34% in those with residual disease in the breast, and in the cN1 subgroup, 30% and 83%, respectively.
When the investigators looked at the extent of nodal burden in cN0 patients with breast pCR, they found the rate of N2 and N3 disease was near zero across all biologic subtypes. “In patients who were cN1 at presentation and achieved a breast pCR but had residual axillary disease, the majority had N1 disease with only 1.5%-4% having four or more positive lymph nodes,” Dr. Barron said.
In the discussion, session moderator Carla Fisher, MD, of Indiana University, Indianapolis, said, “While we might not be ready for prime time to not evaluate the lymph nodes of these patients, this study does speak to the importance of establishing N0 and N1 prior to NAC.” In reply to her question about how Mayo routinely evaluates node status prior to NAC, Dr. Barron noted that Mayo performs routine axillary ultrasound. However, the NCDB data does not specify what imaging was done. This is thought to vary across the centers in the NCDB, Dr. Barron said.
Noted Dr. Boughey, “The findings from this study provide data that can be used moving forward for planning future clinical trials.” She also said that these findings do not alter the current standard of care; that still calls for breast and nodal surgery after NAC. However, the ongoing NRG-BR005 phase II clinical trial is assessing the accuracy of tumor-bed biopsy in these situations (ClinicalTrials.gov Identifier: NCT03188393). “The results from that trial will help inform future trials evaluating eliminating breast surgery in patients with an excellent response to NAC,” Dr. Boughey said. “Those patients could also potentially avoid axillary surgery based on the data we have now.”
Dr. Barron and Dr. Boughey and coauthors reported having no financial disclosures.
SOURCE: Barron AU et al. Society of Surgical Oncology Annual Cancer Symposium, Abstract 48.
CHICAGO – Patients with clinically node-negative HER2-positive or triple-negative breast cancer (TNBC) who achieve a pathological complete response in the breast after neoadjuvant chemotherapy could benefit from clinical trials to evaluate the option of omitting axillary node surgery in this population, according to a retrospective analysis of more than 22,000 cases in the National Cancer Database reported at the Society of Surgical Oncology Annual Cancer Symposium.
Alison U. Barron, MD, breast surgery oncology fellow at Mayo, presented the results. “In patients with HER2+ breast cancer and TNBC who are clinically node negative (cN0) and achieve a breast pathological complete response, this data supports omitting axillary surgery in clinical trials assessing no surgery after neoadjuvant chemotherapy (NAC),” she said. “In patients who present with clinically positive node [cN1] disease with a breast pathological complete response, surgical staging of the axilla is still recommended.”
“Response rates to NAC have increased,” Dr. Barron said. She cited previous reports that showed response rates ranging from 9%-13% for anthracyclines to 19%-26% with the addition of taxanes, and to 60%-70% with the addition of trastuzumab and pertuzumab in HER2+ disease. “Furthermore, we know that tumor biology affects response rates, with TNBC and HER2+ disease having the highest rates of pathologic complete response,” she said.
“In the current era when we frequently operate on patients, we find no residual cancer in the tissue at the time of surgery,” Dr. Barron said. “The question arises as to whether we can limit surgery in patients with a pathological complete response.” While imaging has limited ability to reliably detect pCR with 100% specificity, she noted that recent trials have shown the potential of tumor-bed biopsy to identify pCR in patients after NAC (Ann Surg. Published online Oct. 23, 2017. doi: 10.1097/SLA.0000000000002573; JAMA Surg. 2017;152(7):665-70).
The National Cancer Database data the Mayo researchers analyzed yielded an overall breast pCR of 29%. “When broken down by tumor subtype, we saw significantly higher rates of breast pCR in patients with HER2+ disease (42%, n = 3,107) and TNBC (35%, n = 2,469), compared with patients with hormone-receptor positive (HR+)/HER2-negative disease (12%, n = 1,020),” she said.
When the analysis looked specifically at patients who were clinically node negative at presentation and had a pCR, the rates of positive lymph nodes at the time of surgery were 1.6% in HER2+ patients and 1.7% in TNBC disease, Dr. Barron said. “If there was residual disease in the breast, the nodal positivity rate was significantly higher, at 18% in HER2+ and 12% in TNBC,” she added. In those who were clinical N1, the breast pCR rates were similar – 41% in HER2+ and 35% in TNBC – but nodal positivity rates were significantly higher, at 13% and 14%, respectively.
The HR+/HER2- group had significantly lower rates of pCR: 12% in the cN0 and 13% in the cN1 subgroups. This subgroup also had higher nodal positivity rates – in the cN0 subgroup, 4% in those with a breast pCR and 34% in those with residual disease in the breast, and in the cN1 subgroup, 30% and 83%, respectively.
When the investigators looked at the extent of nodal burden in cN0 patients with breast pCR, they found the rate of N2 and N3 disease was near zero across all biologic subtypes. “In patients who were cN1 at presentation and achieved a breast pCR but had residual axillary disease, the majority had N1 disease with only 1.5%-4% having four or more positive lymph nodes,” Dr. Barron said.
In the discussion, session moderator Carla Fisher, MD, of Indiana University, Indianapolis, said, “While we might not be ready for prime time to not evaluate the lymph nodes of these patients, this study does speak to the importance of establishing N0 and N1 prior to NAC.” In reply to her question about how Mayo routinely evaluates node status prior to NAC, Dr. Barron noted that Mayo performs routine axillary ultrasound. However, the NCDB data does not specify what imaging was done. This is thought to vary across the centers in the NCDB, Dr. Barron said.
Noted Dr. Boughey, “The findings from this study provide data that can be used moving forward for planning future clinical trials.” She also said that these findings do not alter the current standard of care; that still calls for breast and nodal surgery after NAC. However, the ongoing NRG-BR005 phase II clinical trial is assessing the accuracy of tumor-bed biopsy in these situations (ClinicalTrials.gov Identifier: NCT03188393). “The results from that trial will help inform future trials evaluating eliminating breast surgery in patients with an excellent response to NAC,” Dr. Boughey said. “Those patients could also potentially avoid axillary surgery based on the data we have now.”
Dr. Barron and Dr. Boughey and coauthors reported having no financial disclosures.
SOURCE: Barron AU et al. Society of Surgical Oncology Annual Cancer Symposium, Abstract 48.
CHICAGO – Patients with clinically node-negative HER2-positive or triple-negative breast cancer (TNBC) who achieve a pathological complete response in the breast after neoadjuvant chemotherapy could benefit from clinical trials to evaluate the option of omitting axillary node surgery in this population, according to a retrospective analysis of more than 22,000 cases in the National Cancer Database reported at the Society of Surgical Oncology Annual Cancer Symposium.
Alison U. Barron, MD, breast surgery oncology fellow at Mayo, presented the results. “In patients with HER2+ breast cancer and TNBC who are clinically node negative (cN0) and achieve a breast pathological complete response, this data supports omitting axillary surgery in clinical trials assessing no surgery after neoadjuvant chemotherapy (NAC),” she said. “In patients who present with clinically positive node [cN1] disease with a breast pathological complete response, surgical staging of the axilla is still recommended.”
“Response rates to NAC have increased,” Dr. Barron said. She cited previous reports that showed response rates ranging from 9%-13% for anthracyclines to 19%-26% with the addition of taxanes, and to 60%-70% with the addition of trastuzumab and pertuzumab in HER2+ disease. “Furthermore, we know that tumor biology affects response rates, with TNBC and HER2+ disease having the highest rates of pathologic complete response,” she said.
“In the current era when we frequently operate on patients, we find no residual cancer in the tissue at the time of surgery,” Dr. Barron said. “The question arises as to whether we can limit surgery in patients with a pathological complete response.” While imaging has limited ability to reliably detect pCR with 100% specificity, she noted that recent trials have shown the potential of tumor-bed biopsy to identify pCR in patients after NAC (Ann Surg. Published online Oct. 23, 2017. doi: 10.1097/SLA.0000000000002573; JAMA Surg. 2017;152(7):665-70).
The National Cancer Database data the Mayo researchers analyzed yielded an overall breast pCR of 29%. “When broken down by tumor subtype, we saw significantly higher rates of breast pCR in patients with HER2+ disease (42%, n = 3,107) and TNBC (35%, n = 2,469), compared with patients with hormone-receptor positive (HR+)/HER2-negative disease (12%, n = 1,020),” she said.
When the analysis looked specifically at patients who were clinically node negative at presentation and had a pCR, the rates of positive lymph nodes at the time of surgery were 1.6% in HER2+ patients and 1.7% in TNBC disease, Dr. Barron said. “If there was residual disease in the breast, the nodal positivity rate was significantly higher, at 18% in HER2+ and 12% in TNBC,” she added. In those who were clinical N1, the breast pCR rates were similar – 41% in HER2+ and 35% in TNBC – but nodal positivity rates were significantly higher, at 13% and 14%, respectively.
The HR+/HER2- group had significantly lower rates of pCR: 12% in the cN0 and 13% in the cN1 subgroups. This subgroup also had higher nodal positivity rates – in the cN0 subgroup, 4% in those with a breast pCR and 34% in those with residual disease in the breast, and in the cN1 subgroup, 30% and 83%, respectively.
When the investigators looked at the extent of nodal burden in cN0 patients with breast pCR, they found the rate of N2 and N3 disease was near zero across all biologic subtypes. “In patients who were cN1 at presentation and achieved a breast pCR but had residual axillary disease, the majority had N1 disease with only 1.5%-4% having four or more positive lymph nodes,” Dr. Barron said.
In the discussion, session moderator Carla Fisher, MD, of Indiana University, Indianapolis, said, “While we might not be ready for prime time to not evaluate the lymph nodes of these patients, this study does speak to the importance of establishing N0 and N1 prior to NAC.” In reply to her question about how Mayo routinely evaluates node status prior to NAC, Dr. Barron noted that Mayo performs routine axillary ultrasound. However, the NCDB data does not specify what imaging was done. This is thought to vary across the centers in the NCDB, Dr. Barron said.
Noted Dr. Boughey, “The findings from this study provide data that can be used moving forward for planning future clinical trials.” She also said that these findings do not alter the current standard of care; that still calls for breast and nodal surgery after NAC. However, the ongoing NRG-BR005 phase II clinical trial is assessing the accuracy of tumor-bed biopsy in these situations (ClinicalTrials.gov Identifier: NCT03188393). “The results from that trial will help inform future trials evaluating eliminating breast surgery in patients with an excellent response to NAC,” Dr. Boughey said. “Those patients could also potentially avoid axillary surgery based on the data we have now.”
Dr. Barron and Dr. Boughey and coauthors reported having no financial disclosures.
SOURCE: Barron AU et al. Society of Surgical Oncology Annual Cancer Symposium, Abstract 48.
REPORTING FROM SSO 2018
Key clinical point: Neoadjuvant chemotherapy for certain breast cancers achieves low rates of nodal positivity.
Major finding: In clinically node-negative HER2+ and triple-negative disease, nodal positivity after NAC in patients that had breast pathological complete response was less than 2%.
Study details: Review of 22,695 patients in NCDB with clinical T1 or T2 disease from 2010 to 2014.
Disclosure: Dr. Barron and coauthors reported having no financial disclosures.
Source: Barron AU et al. Society of Surgical Oncology Annual Cancer Symposium, Abstract 48.
Hospitalists 'perfectly poised' to drive health care reform
ORLANDO – As dizzying as the alphabet soup of payment reform might seem – with its swirl of new incentives, alignments, and models – hospitalists should already be familiar with many of its main ideas, said keynote speaker Kate Goodrich, MD, director of the Center for Clinical Standards and Quality at the Centers for Medicare and Medicaid Services.
That makes hospitalists poised to help reform a U.S. health care system with the dubious pairing of staggering costs and poor outcomes, Dr. Goodrich told a packed ballroom on Monday at the annual meeting of the Society of Hospital Medicine.
Many of the measures involved in payment reform – with its Merit-Based Incentive Payment System (MIPS), Medicare Access and CHIP Reauthorization Act (MACRA), and Advanced Payment Models (APMs) – focus on outpatient and ambulatory care, Dr. Goodrich acknowledged. But it’s also about medical systems, she said.
“What do you focus on as hospitalists? Improving systems of care,” she said. “We focus on clinical care for our individual patient, but part of our job is also to think about it in terms of how do I improve the care across my hospital system?”
One aspect of reform that is most likely to directly affect hospitalists is the facility-based measurement part of the Quality Payment Program, slated to take effect in 2019. If participating in MIPS – the payment model in which clinicians can receive an increase or decrease in payments based on performance measured by data on quality, cost, and other factors – clinicians can choose to have their hospital’s quality measures count toward their MIPS quality score. The facility measurement was developed in part after conversations between CMS and SHM, Dr. Goodrich said.
“Many stakeholders are very excited about this possibility for a couple of reasons: No. 1, there would be absolutely no quality-reporting burden for you if you chose to do that,” she said. “No. 2, it really aligns the incentives between you and the hospital that you’re working in. Because, after all, we are all in this together. And some folks have felt like they aren’t always aligned with the incentives of the hospital that they are working with, or working for.”
Dr. Goodrich didn’t try to send a message that payment reform isn’t a challenge for hospitalists or anyone else – she called the new system “complicated” and said that “we are in a stage of fairly dramatic health system transformation.”
But she said there are steps hospitalists can take to make quality change – and necessary change – happen.
“First of all, of course, continue to provide high-quality patient care, focus on the patients in front of you, and lead the teams that you need in order to provide high-quality care,” she said.
Also, Dr. Goodrich said, hospitalists should learn to work more closely with their own hospital administrators and the post-acute facilities in their local communities.
“We have to figure out ways to collaborate with them and align the incentives across all of these systems of care,” she said. “Some of that comes top down from payers, but much of that can happen at the local level as well.”
Yet, she noted that she often senses trepidation.
“I always get the question: ‘Well, how do we do this? How do we make this change? It’s not something that we’re necessarily trained for,’ ” Dr. Goodrich said. “There are people out there who are doing this well. This is actually spreading across the country. So seek out those high-performers and learn from them. There’s a lot of learning networks out there that you can access to learn how to make some of these changes.”
ORLANDO – As dizzying as the alphabet soup of payment reform might seem – with its swirl of new incentives, alignments, and models – hospitalists should already be familiar with many of its main ideas, said keynote speaker Kate Goodrich, MD, director of the Center for Clinical Standards and Quality at the Centers for Medicare and Medicaid Services.
That makes hospitalists poised to help reform a U.S. health care system with the dubious pairing of staggering costs and poor outcomes, Dr. Goodrich told a packed ballroom on Monday at the annual meeting of the Society of Hospital Medicine.
Many of the measures involved in payment reform – with its Merit-Based Incentive Payment System (MIPS), Medicare Access and CHIP Reauthorization Act (MACRA), and Advanced Payment Models (APMs) – focus on outpatient and ambulatory care, Dr. Goodrich acknowledged. But it’s also about medical systems, she said.
“What do you focus on as hospitalists? Improving systems of care,” she said. “We focus on clinical care for our individual patient, but part of our job is also to think about it in terms of how do I improve the care across my hospital system?”
One aspect of reform that is most likely to directly affect hospitalists is the facility-based measurement part of the Quality Payment Program, slated to take effect in 2019. If participating in MIPS – the payment model in which clinicians can receive an increase or decrease in payments based on performance measured by data on quality, cost, and other factors – clinicians can choose to have their hospital’s quality measures count toward their MIPS quality score. The facility measurement was developed in part after conversations between CMS and SHM, Dr. Goodrich said.
“Many stakeholders are very excited about this possibility for a couple of reasons: No. 1, there would be absolutely no quality-reporting burden for you if you chose to do that,” she said. “No. 2, it really aligns the incentives between you and the hospital that you’re working in. Because, after all, we are all in this together. And some folks have felt like they aren’t always aligned with the incentives of the hospital that they are working with, or working for.”
Dr. Goodrich didn’t try to send a message that payment reform isn’t a challenge for hospitalists or anyone else – she called the new system “complicated” and said that “we are in a stage of fairly dramatic health system transformation.”
But she said there are steps hospitalists can take to make quality change – and necessary change – happen.
“First of all, of course, continue to provide high-quality patient care, focus on the patients in front of you, and lead the teams that you need in order to provide high-quality care,” she said.
Also, Dr. Goodrich said, hospitalists should learn to work more closely with their own hospital administrators and the post-acute facilities in their local communities.
“We have to figure out ways to collaborate with them and align the incentives across all of these systems of care,” she said. “Some of that comes top down from payers, but much of that can happen at the local level as well.”
Yet, she noted that she often senses trepidation.
“I always get the question: ‘Well, how do we do this? How do we make this change? It’s not something that we’re necessarily trained for,’ ” Dr. Goodrich said. “There are people out there who are doing this well. This is actually spreading across the country. So seek out those high-performers and learn from them. There’s a lot of learning networks out there that you can access to learn how to make some of these changes.”
ORLANDO – As dizzying as the alphabet soup of payment reform might seem – with its swirl of new incentives, alignments, and models – hospitalists should already be familiar with many of its main ideas, said keynote speaker Kate Goodrich, MD, director of the Center for Clinical Standards and Quality at the Centers for Medicare and Medicaid Services.
That makes hospitalists poised to help reform a U.S. health care system with the dubious pairing of staggering costs and poor outcomes, Dr. Goodrich told a packed ballroom on Monday at the annual meeting of the Society of Hospital Medicine.
Many of the measures involved in payment reform – with its Merit-Based Incentive Payment System (MIPS), Medicare Access and CHIP Reauthorization Act (MACRA), and Advanced Payment Models (APMs) – focus on outpatient and ambulatory care, Dr. Goodrich acknowledged. But it’s also about medical systems, she said.
“What do you focus on as hospitalists? Improving systems of care,” she said. “We focus on clinical care for our individual patient, but part of our job is also to think about it in terms of how do I improve the care across my hospital system?”
One aspect of reform that is most likely to directly affect hospitalists is the facility-based measurement part of the Quality Payment Program, slated to take effect in 2019. If participating in MIPS – the payment model in which clinicians can receive an increase or decrease in payments based on performance measured by data on quality, cost, and other factors – clinicians can choose to have their hospital’s quality measures count toward their MIPS quality score. The facility measurement was developed in part after conversations between CMS and SHM, Dr. Goodrich said.
“Many stakeholders are very excited about this possibility for a couple of reasons: No. 1, there would be absolutely no quality-reporting burden for you if you chose to do that,” she said. “No. 2, it really aligns the incentives between you and the hospital that you’re working in. Because, after all, we are all in this together. And some folks have felt like they aren’t always aligned with the incentives of the hospital that they are working with, or working for.”
Dr. Goodrich didn’t try to send a message that payment reform isn’t a challenge for hospitalists or anyone else – she called the new system “complicated” and said that “we are in a stage of fairly dramatic health system transformation.”
But she said there are steps hospitalists can take to make quality change – and necessary change – happen.
“First of all, of course, continue to provide high-quality patient care, focus on the patients in front of you, and lead the teams that you need in order to provide high-quality care,” she said.
Also, Dr. Goodrich said, hospitalists should learn to work more closely with their own hospital administrators and the post-acute facilities in their local communities.
“We have to figure out ways to collaborate with them and align the incentives across all of these systems of care,” she said. “Some of that comes top down from payers, but much of that can happen at the local level as well.”
Yet, she noted that she often senses trepidation.
“I always get the question: ‘Well, how do we do this? How do we make this change? It’s not something that we’re necessarily trained for,’ ” Dr. Goodrich said. “There are people out there who are doing this well. This is actually spreading across the country. So seek out those high-performers and learn from them. There’s a lot of learning networks out there that you can access to learn how to make some of these changes.”
Cancer-related clinical pearls from pediatric dermatology
KAUAI, HAWAII – Every child diagnosed with medulloblastoma deserves a careful dermatologic evaluation for possible comorbid basal cell nevus syndrome, according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital and Harvard Medical School.
“Medulloblastoma occurs in 10%-20% of patients with basal cell nevus syndrome and can be the presenting sign. So if a patient with basal cell nevus syndrome gets medulloblastoma, it usually occurs within the first year of life – and it can be the first thing you see,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Huang presented a series of pediatric dermatology clinical pearls focused not only on basal cell nevus syndrome (BCNS) and medulloblastoma, but also on the implications of skin-limited Langerhans cell histiocytosis, how to recognize and treat drug-induced follicular eruptions in pediatric patients on targeted anticancer therapies, and when to suspect Demodex folliculitis in immunosuppressed patients.
Skin-limited Langerhans cell histiocytosis
Around 10%-20% of patients with Langerhans cell histiocytosis (LCH) have the skin-limited form of the malignancy. These are patients who, after a thorough workup, have a normal CBC, skeletal survey, and liver function tests; essentially, no evidence of multisystem disease.
“It’s very rare for patients who present with skin-limited LCH alone to develop multisystem disease and to require chemotherapy or other more aggressive treatment,” Dr. Huang said. “I think that skin-limited LCH is probably a separate entity with its own natural history distinct from multisystem disease. We can see that with current genomic testing: in multisystem LCH, BRAF mutations are identified in at least half of patients, but very few with skin-limited disease express those mutations.
“The clinical pearl here is if you have a patient with skin-limited LCH it very rarely progresses to multisystem involvement. It’s associated with a good prognosis. That doesn’t mean you shouldn’t monitor them, but I think it can be reassuring information for the family,” she said.
Basal cell nevus syndrome and medulloblastoma
“Half of cases of medulloblastoma are associated with mutations in the sonic hedgehog pathway – and a subset of that group has basal cell nevus syndrome,” Dr. Huang said.
BCNS is not a diagnosis frequently made by oncologists, who typically dismiss the multitude of lesions as skin tags, which they often mimic in both appearance and location, particularly on the neck and intertriginous areas. So it’s useful for dermatologists to establish a good referral relationship with their local oncologists.
“As dermatologists it’s really important to recognize not only the major features of basal cell nevus syndrome, but also the associated findings because we can really help in making this diagnosis early,” Dr. Huang stressed.
Early diagnosis of BCNS is a high priority for two reasons: to start treatment aimed at reducing development of basal cell carcinomas, and because radiation therapy for their medulloblastoma is contraindicated in patients with BCNS because it boosts their skin cancer burden.
BCNS is caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. The major features of BCNS include odontogenic keratocysts, palmoplantar pits, ectopic calcification, and, of course, basal cell carcinomas. The associated findings in BCNS, in addition to medulloblastoma, include macrocephaly and dysmorphic features such as cleft lip or palate, frontal bossing, and hypertelorism.
“I’ve treated a hundred at a time. It’s incredibly successful. It’s locally destructive. It leaves a little bit of hypopigmentation but no scar, which the CO2 laser will do in this instance. It’s actually a pretty cool modality,” said Dr. Eichenfield, professor of dermatology and pediatrics at Rady Children’s Hospital and the University of California, San Diego.
Follicular eruptions in cancer patients on MAPK inhibitors
Cutaneous reactions to anticancer drugs aimed at inhibiting the key MAPK (mitogen-activated protein kinase) pathway in children are common and diverse. Dr. Huang focused on the most common one: follicular eruptions, which occur in up to 80% of pediatric cancer patients on targeted therapy. These eruptions can express themselves in a variety of ways and are easily mistaken for comedonal acne, varicella zoster infection, herpes simplex, or bacterial folliculitis.
The key clues are highly suggestive that a follicular eruption in a child on targeted anticancer therapy is caused by the drug and not something else are the eruption’s symmetric distribution, that it’s truly follicular upon close inspection, and the timing: The eruption typically begins 2-3 weeks after initiation of therapy or within a week after a dose escalation.
Anti-inflammatory agents are the treatment mainstay. Treatment of the cutaneous eruption often is successful without need to discontinue the patient’s MAPK inhibitor.
“Even though some of these eruptions look comedonal, they’re not. It’s not a follicular plugging disorder, it’s an inflammatory condition. Topical steroids, oral tetracyclines, and dilute bleach baths all work pretty well. I haven’t had good experiences with keratolytics like tretinoin cream and benzoyl peroxide; they’re less effective. Dose reduction is the last resort for these patients. Often they are very sick. They need the drug and I think the last thing we want to do is take them off it,” Dr. Huang said.
She has observed that prepubertal children are more likely to have an eczematous reaction to their targeted anticancer therapy than a follicular eruption.
D. folliculitis in immunocompromised patients
“The clinical pearl here is to strongly consider the diagnosis of Demodex folliculitis in an immunosuppresed patient with an itchy acneiform eruption,” Dr. Huang said.
Demodex is a human mite which is part of the normal skin flora. She called it “a great mimicker”: It can cause dermatoses mistaken for rosacea, acne, seborrheic dermatitis, perioral facial dermatitis, blepharitis, and acute graft-versus-host disease.
In the setting of a young, immunosuppressed patient who develops an acneiform eruption, the differential diagnosis is lengthy and includes steroid-induced acne, a cutaneous reaction to targeted anticancer therapy, gram-negative folliculitis secondary to long-term antibiotic therapy, and Pityrosporum folliculitis, as well as D. folliculitis.
Demodex and P. folliculitis are the two acneiform dermatoses where itch figures prominently. A couple of clues are helpful in differentiating the two conditions: P. folliculitis often involves the chest and back, while D. folliculitis generally spares the trunk and is focused on the face and neck. And D. folliculitis typically arises when immunosuppression is weaned. Overgrowth of the mites occurs during immunosuppression, then as the immunosuppression is lifted a prominent inflammatory response with an acne-like appearance occurs.
Dr. Huang usually sticks with topical therapies for D. folliculitis. These include topical sulfur 5%, permethrin 5%, metronidazole, and/or ivermectin. If a young patient is unresponsive to this panoply of topical agents, she resorts to a single dose of oral ivermectin at 0.2 mg/kg, usually with good effect.
Dr. Huang reported having no financial conflicts of interest regarding her presentation.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Every child diagnosed with medulloblastoma deserves a careful dermatologic evaluation for possible comorbid basal cell nevus syndrome, according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital and Harvard Medical School.
“Medulloblastoma occurs in 10%-20% of patients with basal cell nevus syndrome and can be the presenting sign. So if a patient with basal cell nevus syndrome gets medulloblastoma, it usually occurs within the first year of life – and it can be the first thing you see,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Huang presented a series of pediatric dermatology clinical pearls focused not only on basal cell nevus syndrome (BCNS) and medulloblastoma, but also on the implications of skin-limited Langerhans cell histiocytosis, how to recognize and treat drug-induced follicular eruptions in pediatric patients on targeted anticancer therapies, and when to suspect Demodex folliculitis in immunosuppressed patients.
Skin-limited Langerhans cell histiocytosis
Around 10%-20% of patients with Langerhans cell histiocytosis (LCH) have the skin-limited form of the malignancy. These are patients who, after a thorough workup, have a normal CBC, skeletal survey, and liver function tests; essentially, no evidence of multisystem disease.
“It’s very rare for patients who present with skin-limited LCH alone to develop multisystem disease and to require chemotherapy or other more aggressive treatment,” Dr. Huang said. “I think that skin-limited LCH is probably a separate entity with its own natural history distinct from multisystem disease. We can see that with current genomic testing: in multisystem LCH, BRAF mutations are identified in at least half of patients, but very few with skin-limited disease express those mutations.
“The clinical pearl here is if you have a patient with skin-limited LCH it very rarely progresses to multisystem involvement. It’s associated with a good prognosis. That doesn’t mean you shouldn’t monitor them, but I think it can be reassuring information for the family,” she said.
Basal cell nevus syndrome and medulloblastoma
“Half of cases of medulloblastoma are associated with mutations in the sonic hedgehog pathway – and a subset of that group has basal cell nevus syndrome,” Dr. Huang said.
BCNS is not a diagnosis frequently made by oncologists, who typically dismiss the multitude of lesions as skin tags, which they often mimic in both appearance and location, particularly on the neck and intertriginous areas. So it’s useful for dermatologists to establish a good referral relationship with their local oncologists.
“As dermatologists it’s really important to recognize not only the major features of basal cell nevus syndrome, but also the associated findings because we can really help in making this diagnosis early,” Dr. Huang stressed.
Early diagnosis of BCNS is a high priority for two reasons: to start treatment aimed at reducing development of basal cell carcinomas, and because radiation therapy for their medulloblastoma is contraindicated in patients with BCNS because it boosts their skin cancer burden.
BCNS is caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. The major features of BCNS include odontogenic keratocysts, palmoplantar pits, ectopic calcification, and, of course, basal cell carcinomas. The associated findings in BCNS, in addition to medulloblastoma, include macrocephaly and dysmorphic features such as cleft lip or palate, frontal bossing, and hypertelorism.
“I’ve treated a hundred at a time. It’s incredibly successful. It’s locally destructive. It leaves a little bit of hypopigmentation but no scar, which the CO2 laser will do in this instance. It’s actually a pretty cool modality,” said Dr. Eichenfield, professor of dermatology and pediatrics at Rady Children’s Hospital and the University of California, San Diego.
Follicular eruptions in cancer patients on MAPK inhibitors
Cutaneous reactions to anticancer drugs aimed at inhibiting the key MAPK (mitogen-activated protein kinase) pathway in children are common and diverse. Dr. Huang focused on the most common one: follicular eruptions, which occur in up to 80% of pediatric cancer patients on targeted therapy. These eruptions can express themselves in a variety of ways and are easily mistaken for comedonal acne, varicella zoster infection, herpes simplex, or bacterial folliculitis.
The key clues are highly suggestive that a follicular eruption in a child on targeted anticancer therapy is caused by the drug and not something else are the eruption’s symmetric distribution, that it’s truly follicular upon close inspection, and the timing: The eruption typically begins 2-3 weeks after initiation of therapy or within a week after a dose escalation.
Anti-inflammatory agents are the treatment mainstay. Treatment of the cutaneous eruption often is successful without need to discontinue the patient’s MAPK inhibitor.
“Even though some of these eruptions look comedonal, they’re not. It’s not a follicular plugging disorder, it’s an inflammatory condition. Topical steroids, oral tetracyclines, and dilute bleach baths all work pretty well. I haven’t had good experiences with keratolytics like tretinoin cream and benzoyl peroxide; they’re less effective. Dose reduction is the last resort for these patients. Often they are very sick. They need the drug and I think the last thing we want to do is take them off it,” Dr. Huang said.
She has observed that prepubertal children are more likely to have an eczematous reaction to their targeted anticancer therapy than a follicular eruption.
D. folliculitis in immunocompromised patients
“The clinical pearl here is to strongly consider the diagnosis of Demodex folliculitis in an immunosuppresed patient with an itchy acneiform eruption,” Dr. Huang said.
Demodex is a human mite which is part of the normal skin flora. She called it “a great mimicker”: It can cause dermatoses mistaken for rosacea, acne, seborrheic dermatitis, perioral facial dermatitis, blepharitis, and acute graft-versus-host disease.
In the setting of a young, immunosuppressed patient who develops an acneiform eruption, the differential diagnosis is lengthy and includes steroid-induced acne, a cutaneous reaction to targeted anticancer therapy, gram-negative folliculitis secondary to long-term antibiotic therapy, and Pityrosporum folliculitis, as well as D. folliculitis.
Demodex and P. folliculitis are the two acneiform dermatoses where itch figures prominently. A couple of clues are helpful in differentiating the two conditions: P. folliculitis often involves the chest and back, while D. folliculitis generally spares the trunk and is focused on the face and neck. And D. folliculitis typically arises when immunosuppression is weaned. Overgrowth of the mites occurs during immunosuppression, then as the immunosuppression is lifted a prominent inflammatory response with an acne-like appearance occurs.
Dr. Huang usually sticks with topical therapies for D. folliculitis. These include topical sulfur 5%, permethrin 5%, metronidazole, and/or ivermectin. If a young patient is unresponsive to this panoply of topical agents, she resorts to a single dose of oral ivermectin at 0.2 mg/kg, usually with good effect.
Dr. Huang reported having no financial conflicts of interest regarding her presentation.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Every child diagnosed with medulloblastoma deserves a careful dermatologic evaluation for possible comorbid basal cell nevus syndrome, according to Jennifer Huang, MD, a pediatric dermatologist at Boston Children’s Hospital and Harvard Medical School.
“Medulloblastoma occurs in 10%-20% of patients with basal cell nevus syndrome and can be the presenting sign. So if a patient with basal cell nevus syndrome gets medulloblastoma, it usually occurs within the first year of life – and it can be the first thing you see,” she said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Dr. Huang presented a series of pediatric dermatology clinical pearls focused not only on basal cell nevus syndrome (BCNS) and medulloblastoma, but also on the implications of skin-limited Langerhans cell histiocytosis, how to recognize and treat drug-induced follicular eruptions in pediatric patients on targeted anticancer therapies, and when to suspect Demodex folliculitis in immunosuppressed patients.
Skin-limited Langerhans cell histiocytosis
Around 10%-20% of patients with Langerhans cell histiocytosis (LCH) have the skin-limited form of the malignancy. These are patients who, after a thorough workup, have a normal CBC, skeletal survey, and liver function tests; essentially, no evidence of multisystem disease.
“It’s very rare for patients who present with skin-limited LCH alone to develop multisystem disease and to require chemotherapy or other more aggressive treatment,” Dr. Huang said. “I think that skin-limited LCH is probably a separate entity with its own natural history distinct from multisystem disease. We can see that with current genomic testing: in multisystem LCH, BRAF mutations are identified in at least half of patients, but very few with skin-limited disease express those mutations.
“The clinical pearl here is if you have a patient with skin-limited LCH it very rarely progresses to multisystem involvement. It’s associated with a good prognosis. That doesn’t mean you shouldn’t monitor them, but I think it can be reassuring information for the family,” she said.
Basal cell nevus syndrome and medulloblastoma
“Half of cases of medulloblastoma are associated with mutations in the sonic hedgehog pathway – and a subset of that group has basal cell nevus syndrome,” Dr. Huang said.
BCNS is not a diagnosis frequently made by oncologists, who typically dismiss the multitude of lesions as skin tags, which they often mimic in both appearance and location, particularly on the neck and intertriginous areas. So it’s useful for dermatologists to establish a good referral relationship with their local oncologists.
“As dermatologists it’s really important to recognize not only the major features of basal cell nevus syndrome, but also the associated findings because we can really help in making this diagnosis early,” Dr. Huang stressed.
Early diagnosis of BCNS is a high priority for two reasons: to start treatment aimed at reducing development of basal cell carcinomas, and because radiation therapy for their medulloblastoma is contraindicated in patients with BCNS because it boosts their skin cancer burden.
BCNS is caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. The major features of BCNS include odontogenic keratocysts, palmoplantar pits, ectopic calcification, and, of course, basal cell carcinomas. The associated findings in BCNS, in addition to medulloblastoma, include macrocephaly and dysmorphic features such as cleft lip or palate, frontal bossing, and hypertelorism.
“I’ve treated a hundred at a time. It’s incredibly successful. It’s locally destructive. It leaves a little bit of hypopigmentation but no scar, which the CO2 laser will do in this instance. It’s actually a pretty cool modality,” said Dr. Eichenfield, professor of dermatology and pediatrics at Rady Children’s Hospital and the University of California, San Diego.
Follicular eruptions in cancer patients on MAPK inhibitors
Cutaneous reactions to anticancer drugs aimed at inhibiting the key MAPK (mitogen-activated protein kinase) pathway in children are common and diverse. Dr. Huang focused on the most common one: follicular eruptions, which occur in up to 80% of pediatric cancer patients on targeted therapy. These eruptions can express themselves in a variety of ways and are easily mistaken for comedonal acne, varicella zoster infection, herpes simplex, or bacterial folliculitis.
The key clues are highly suggestive that a follicular eruption in a child on targeted anticancer therapy is caused by the drug and not something else are the eruption’s symmetric distribution, that it’s truly follicular upon close inspection, and the timing: The eruption typically begins 2-3 weeks after initiation of therapy or within a week after a dose escalation.
Anti-inflammatory agents are the treatment mainstay. Treatment of the cutaneous eruption often is successful without need to discontinue the patient’s MAPK inhibitor.
“Even though some of these eruptions look comedonal, they’re not. It’s not a follicular plugging disorder, it’s an inflammatory condition. Topical steroids, oral tetracyclines, and dilute bleach baths all work pretty well. I haven’t had good experiences with keratolytics like tretinoin cream and benzoyl peroxide; they’re less effective. Dose reduction is the last resort for these patients. Often they are very sick. They need the drug and I think the last thing we want to do is take them off it,” Dr. Huang said.
She has observed that prepubertal children are more likely to have an eczematous reaction to their targeted anticancer therapy than a follicular eruption.
D. folliculitis in immunocompromised patients
“The clinical pearl here is to strongly consider the diagnosis of Demodex folliculitis in an immunosuppresed patient with an itchy acneiform eruption,” Dr. Huang said.
Demodex is a human mite which is part of the normal skin flora. She called it “a great mimicker”: It can cause dermatoses mistaken for rosacea, acne, seborrheic dermatitis, perioral facial dermatitis, blepharitis, and acute graft-versus-host disease.
In the setting of a young, immunosuppressed patient who develops an acneiform eruption, the differential diagnosis is lengthy and includes steroid-induced acne, a cutaneous reaction to targeted anticancer therapy, gram-negative folliculitis secondary to long-term antibiotic therapy, and Pityrosporum folliculitis, as well as D. folliculitis.
Demodex and P. folliculitis are the two acneiform dermatoses where itch figures prominently. A couple of clues are helpful in differentiating the two conditions: P. folliculitis often involves the chest and back, while D. folliculitis generally spares the trunk and is focused on the face and neck. And D. folliculitis typically arises when immunosuppression is weaned. Overgrowth of the mites occurs during immunosuppression, then as the immunosuppression is lifted a prominent inflammatory response with an acne-like appearance occurs.
Dr. Huang usually sticks with topical therapies for D. folliculitis. These include topical sulfur 5%, permethrin 5%, metronidazole, and/or ivermectin. If a young patient is unresponsive to this panoply of topical agents, she resorts to a single dose of oral ivermectin at 0.2 mg/kg, usually with good effect.
Dr. Huang reported having no financial conflicts of interest regarding her presentation.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
EAGLES: Smoking cessation therapy did not up cardiovascular risk
among stable adult smokers with up to one year of follow-up.
“In what we believe to be the largest smoking cessation clinical trial and the only trial comparing NRT, bupropion, and varenicline [with] placebo, we found no signal that smoking cessation pharmacotherapy increases the risk of serious cardiovascular disease or cardiovascular adverse events in a general population of smokers,” concluded Neal L. Benowitz, MD, of the University of California, San Francisco, and his associates. “While the number of events was small, the incidence of serious cardiovascular events was low, suggesting that any absolute increase in risk that we might have missed would be low and not clinically meaningful.” The findings were reported online April 9 in JAMA Internal Medicine.
In this double-blind, multicenter, triple-dummy trial (EAGLES), Dr. Benowitz and his associates randomly assigned 8,058 adult smokers, who did not have acute or unstable cardiovascular disease, to receive bupropion (150 mg twice daily), varenicline (1 mg twice daily), NRT (21-mg/day patch with tapering), or placebo for 12 weeks, followed by 12 weeks of follow-up. A total of 4,595 patients agreed to be followed for another 28 weeks during an extension phase of the trial. More than half of the patients were women and the average age of a participant was 47 years. The primary endpoint was time to major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The researchers selected time to MACE as their primary endpoint to better detect differences among groups. One of the secondary end points was the occurrence of MACEs over the same 3 time intervals. Additionally, cardiovascular deaths, nonfatal MI, and nonfatal stroke (the components of MACE) were evaluated individually, as were hospitalizations for congestive heart failure and serious arrhythmias.
Differences in time to onset of MACE between all four patient groups, were not significant. The overall incidence of MACEs was less than 0.5% during all observation periods. There were also no significant differences in rates of the individual types of MACE, coronary revascularization, hospitalization for unstable angina, or new or worsening peripheral vascular disease requiring treatment among groups. Changes in body weight, blood pressure, and heart rate also were similar across patients.
There were five cardiovascular deaths, including one in the varenicline group, two in the bupropion group and two in the placebo group, according to the researchers. Overall the trial results “are consistent with and support previously published findings from meta-analyses and small clinical trials in smokers with known [cardiovascular disease],” they wrote.
GlaxoSmithKline and Pfizer, who make and market smoking cessation therapies, sponsored the study. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
SOURCE: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397)
among stable adult smokers with up to one year of follow-up.
“In what we believe to be the largest smoking cessation clinical trial and the only trial comparing NRT, bupropion, and varenicline [with] placebo, we found no signal that smoking cessation pharmacotherapy increases the risk of serious cardiovascular disease or cardiovascular adverse events in a general population of smokers,” concluded Neal L. Benowitz, MD, of the University of California, San Francisco, and his associates. “While the number of events was small, the incidence of serious cardiovascular events was low, suggesting that any absolute increase in risk that we might have missed would be low and not clinically meaningful.” The findings were reported online April 9 in JAMA Internal Medicine.
In this double-blind, multicenter, triple-dummy trial (EAGLES), Dr. Benowitz and his associates randomly assigned 8,058 adult smokers, who did not have acute or unstable cardiovascular disease, to receive bupropion (150 mg twice daily), varenicline (1 mg twice daily), NRT (21-mg/day patch with tapering), or placebo for 12 weeks, followed by 12 weeks of follow-up. A total of 4,595 patients agreed to be followed for another 28 weeks during an extension phase of the trial. More than half of the patients were women and the average age of a participant was 47 years. The primary endpoint was time to major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The researchers selected time to MACE as their primary endpoint to better detect differences among groups. One of the secondary end points was the occurrence of MACEs over the same 3 time intervals. Additionally, cardiovascular deaths, nonfatal MI, and nonfatal stroke (the components of MACE) were evaluated individually, as were hospitalizations for congestive heart failure and serious arrhythmias.
Differences in time to onset of MACE between all four patient groups, were not significant. The overall incidence of MACEs was less than 0.5% during all observation periods. There were also no significant differences in rates of the individual types of MACE, coronary revascularization, hospitalization for unstable angina, or new or worsening peripheral vascular disease requiring treatment among groups. Changes in body weight, blood pressure, and heart rate also were similar across patients.
There were five cardiovascular deaths, including one in the varenicline group, two in the bupropion group and two in the placebo group, according to the researchers. Overall the trial results “are consistent with and support previously published findings from meta-analyses and small clinical trials in smokers with known [cardiovascular disease],” they wrote.
GlaxoSmithKline and Pfizer, who make and market smoking cessation therapies, sponsored the study. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
SOURCE: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397)
among stable adult smokers with up to one year of follow-up.
“In what we believe to be the largest smoking cessation clinical trial and the only trial comparing NRT, bupropion, and varenicline [with] placebo, we found no signal that smoking cessation pharmacotherapy increases the risk of serious cardiovascular disease or cardiovascular adverse events in a general population of smokers,” concluded Neal L. Benowitz, MD, of the University of California, San Francisco, and his associates. “While the number of events was small, the incidence of serious cardiovascular events was low, suggesting that any absolute increase in risk that we might have missed would be low and not clinically meaningful.” The findings were reported online April 9 in JAMA Internal Medicine.
In this double-blind, multicenter, triple-dummy trial (EAGLES), Dr. Benowitz and his associates randomly assigned 8,058 adult smokers, who did not have acute or unstable cardiovascular disease, to receive bupropion (150 mg twice daily), varenicline (1 mg twice daily), NRT (21-mg/day patch with tapering), or placebo for 12 weeks, followed by 12 weeks of follow-up. A total of 4,595 patients agreed to be followed for another 28 weeks during an extension phase of the trial. More than half of the patients were women and the average age of a participant was 47 years. The primary endpoint was time to major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The researchers selected time to MACE as their primary endpoint to better detect differences among groups. One of the secondary end points was the occurrence of MACEs over the same 3 time intervals. Additionally, cardiovascular deaths, nonfatal MI, and nonfatal stroke (the components of MACE) were evaluated individually, as were hospitalizations for congestive heart failure and serious arrhythmias.
Differences in time to onset of MACE between all four patient groups, were not significant. The overall incidence of MACEs was less than 0.5% during all observation periods. There were also no significant differences in rates of the individual types of MACE, coronary revascularization, hospitalization for unstable angina, or new or worsening peripheral vascular disease requiring treatment among groups. Changes in body weight, blood pressure, and heart rate also were similar across patients.
There were five cardiovascular deaths, including one in the varenicline group, two in the bupropion group and two in the placebo group, according to the researchers. Overall the trial results “are consistent with and support previously published findings from meta-analyses and small clinical trials in smokers with known [cardiovascular disease],” they wrote.
GlaxoSmithKline and Pfizer, who make and market smoking cessation therapies, sponsored the study. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
SOURCE: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397)
FROM JAMA INTERNAL MEDICINE
Key clinical point: The use of smoking cessation therapy did not increase the risk of cardiovascular events in adult smokers.
Major finding: There were no significant differences among groups in rates of major adverse cardiovascular events, rates of other pertinent cardiovascular events, time to cardiovascular events, blood pressure, or heart rate.
Study details: Double-blind, randomized, multicenter, triple-dummy trial of 8,058 adult smokers receiving nicotine replacement therapy, bupropion, varenicline, or placebo (EAGLES).
Disclosures: GlaxoSmithKline and Pfizer sponsored the study and make the drugs. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
Source: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397.
Epilepsy upped risk of unnatural death
People with epilepsy were about three times more likely to die from unnatural causes and five times more likely to die from unintentional medication poisoning than controls in a large study.
Opioid and psychotropic drugs were the main sources of poisoning deaths, said Hayley C. Gorton, PhD, of the University of Manchester, England, and her associates. Epilepsy also was associated with a twofold increase in risk of suicide. Providers should counsel patients with epilepsy about unintentional injuries, exercise caution when prescribing opioids, and monitor patients closely for suicidal thoughts, ideation, and behavior, the researchers wrote online April 9 in JAMA Neurology.
The study included 58,729 individuals with epilepsy and nearly 1.2 million controls matched by age, sex, and location. Data sources included the Clinical Practice Research Datalink in England and the Secure Anonymised Information Linkage Databank in Wales. The researchers identified unnatural deaths by querying relevant codes from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The study spanned 1998-2014, with typically 4-8 years of follow-up.
Epilepsy was associated with a significantly increased risk of death from any unnatural cause (hazard ratio, 2.8; 95% confidence interval, 2.4-3.3), from accidental medication poisoning (HR, 5.0; 95% CI, 3.2-7.7), and from suicide (HR, 2.2; 95% CI, 1.5-3.1). Opioids were the most common cause of death from medication poisoning (56%), followed by psychotropic drugs (32%). Antiepileptic drugs were responsible for only about 10% of iatrogenic deaths.
As in prior studies, epilepsy was tied to numerous psychiatric comorbidities, including substance abuse disorders, anxiety, mood and eating disorders, personality disorders, and schizophrenia. Mental illness increases the risk of unintentional injury, poisoning, and suicide, the investigators noted. Mental illness and associated stigma also explain why epilepsy patients were three times more likely to die from homicide (HR, 3.5; 95% CI, 1.2-10.6), they wrote.
Funders included the National Institute for Health Research and Health and Care Research Wales. The researchers reported having no conflicts of interest.
SOURCE: Gorton HC et al. JAMA Neurol. 2019 Apr 9. doi: 10.1001/jamaneurol.2018.0333.
The study elucidates “an enormous problem hiding in plain sight” – persistently high rates of unnatural and medication-induced death among people with epilepsy, wrote Orrin Devinsky, MD, Anuradha Singh, MD, and Daniel Friedman, MD, in an accompanying editorial in JAMA Neurology.
“We need a new paradigm to ‘see’ patients and ‘understand’ their disorders and experiences,” the editorialists explained. Mood disorders, poor judgment, impulsive behavior, and cognitive impairment “are part of the disease biology as much as brain stem cardiopulmonary dysfunction is thought to contribute to sudden unexpected death in epilepsy.”
They called on the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke to encourage studies of “the tangled thicket where neurology and psychiatry meet.”
All three physicians are at NYU Langone Medical Center, New York. Dr. Devinsky disclosed ties to GW Pharmaceuticals and several other companies. No other disclosures were reported (JAMA Neurol. 2018 Apr 9. doi: 10.1001/jamaneurol.2018.0002).
The study elucidates “an enormous problem hiding in plain sight” – persistently high rates of unnatural and medication-induced death among people with epilepsy, wrote Orrin Devinsky, MD, Anuradha Singh, MD, and Daniel Friedman, MD, in an accompanying editorial in JAMA Neurology.
“We need a new paradigm to ‘see’ patients and ‘understand’ their disorders and experiences,” the editorialists explained. Mood disorders, poor judgment, impulsive behavior, and cognitive impairment “are part of the disease biology as much as brain stem cardiopulmonary dysfunction is thought to contribute to sudden unexpected death in epilepsy.”
They called on the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke to encourage studies of “the tangled thicket where neurology and psychiatry meet.”
All three physicians are at NYU Langone Medical Center, New York. Dr. Devinsky disclosed ties to GW Pharmaceuticals and several other companies. No other disclosures were reported (JAMA Neurol. 2018 Apr 9. doi: 10.1001/jamaneurol.2018.0002).
The study elucidates “an enormous problem hiding in plain sight” – persistently high rates of unnatural and medication-induced death among people with epilepsy, wrote Orrin Devinsky, MD, Anuradha Singh, MD, and Daniel Friedman, MD, in an accompanying editorial in JAMA Neurology.
“We need a new paradigm to ‘see’ patients and ‘understand’ their disorders and experiences,” the editorialists explained. Mood disorders, poor judgment, impulsive behavior, and cognitive impairment “are part of the disease biology as much as brain stem cardiopulmonary dysfunction is thought to contribute to sudden unexpected death in epilepsy.”
They called on the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke to encourage studies of “the tangled thicket where neurology and psychiatry meet.”
All three physicians are at NYU Langone Medical Center, New York. Dr. Devinsky disclosed ties to GW Pharmaceuticals and several other companies. No other disclosures were reported (JAMA Neurol. 2018 Apr 9. doi: 10.1001/jamaneurol.2018.0002).
People with epilepsy were about three times more likely to die from unnatural causes and five times more likely to die from unintentional medication poisoning than controls in a large study.
Opioid and psychotropic drugs were the main sources of poisoning deaths, said Hayley C. Gorton, PhD, of the University of Manchester, England, and her associates. Epilepsy also was associated with a twofold increase in risk of suicide. Providers should counsel patients with epilepsy about unintentional injuries, exercise caution when prescribing opioids, and monitor patients closely for suicidal thoughts, ideation, and behavior, the researchers wrote online April 9 in JAMA Neurology.
The study included 58,729 individuals with epilepsy and nearly 1.2 million controls matched by age, sex, and location. Data sources included the Clinical Practice Research Datalink in England and the Secure Anonymised Information Linkage Databank in Wales. The researchers identified unnatural deaths by querying relevant codes from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The study spanned 1998-2014, with typically 4-8 years of follow-up.
Epilepsy was associated with a significantly increased risk of death from any unnatural cause (hazard ratio, 2.8; 95% confidence interval, 2.4-3.3), from accidental medication poisoning (HR, 5.0; 95% CI, 3.2-7.7), and from suicide (HR, 2.2; 95% CI, 1.5-3.1). Opioids were the most common cause of death from medication poisoning (56%), followed by psychotropic drugs (32%). Antiepileptic drugs were responsible for only about 10% of iatrogenic deaths.
As in prior studies, epilepsy was tied to numerous psychiatric comorbidities, including substance abuse disorders, anxiety, mood and eating disorders, personality disorders, and schizophrenia. Mental illness increases the risk of unintentional injury, poisoning, and suicide, the investigators noted. Mental illness and associated stigma also explain why epilepsy patients were three times more likely to die from homicide (HR, 3.5; 95% CI, 1.2-10.6), they wrote.
Funders included the National Institute for Health Research and Health and Care Research Wales. The researchers reported having no conflicts of interest.
SOURCE: Gorton HC et al. JAMA Neurol. 2019 Apr 9. doi: 10.1001/jamaneurol.2018.0333.
People with epilepsy were about three times more likely to die from unnatural causes and five times more likely to die from unintentional medication poisoning than controls in a large study.
Opioid and psychotropic drugs were the main sources of poisoning deaths, said Hayley C. Gorton, PhD, of the University of Manchester, England, and her associates. Epilepsy also was associated with a twofold increase in risk of suicide. Providers should counsel patients with epilepsy about unintentional injuries, exercise caution when prescribing opioids, and monitor patients closely for suicidal thoughts, ideation, and behavior, the researchers wrote online April 9 in JAMA Neurology.
The study included 58,729 individuals with epilepsy and nearly 1.2 million controls matched by age, sex, and location. Data sources included the Clinical Practice Research Datalink in England and the Secure Anonymised Information Linkage Databank in Wales. The researchers identified unnatural deaths by querying relevant codes from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The study spanned 1998-2014, with typically 4-8 years of follow-up.
Epilepsy was associated with a significantly increased risk of death from any unnatural cause (hazard ratio, 2.8; 95% confidence interval, 2.4-3.3), from accidental medication poisoning (HR, 5.0; 95% CI, 3.2-7.7), and from suicide (HR, 2.2; 95% CI, 1.5-3.1). Opioids were the most common cause of death from medication poisoning (56%), followed by psychotropic drugs (32%). Antiepileptic drugs were responsible for only about 10% of iatrogenic deaths.
As in prior studies, epilepsy was tied to numerous psychiatric comorbidities, including substance abuse disorders, anxiety, mood and eating disorders, personality disorders, and schizophrenia. Mental illness increases the risk of unintentional injury, poisoning, and suicide, the investigators noted. Mental illness and associated stigma also explain why epilepsy patients were three times more likely to die from homicide (HR, 3.5; 95% CI, 1.2-10.6), they wrote.
Funders included the National Institute for Health Research and Health and Care Research Wales. The researchers reported having no conflicts of interest.
SOURCE: Gorton HC et al. JAMA Neurol. 2019 Apr 9. doi: 10.1001/jamaneurol.2018.0333.
FROM JAMA NEUROLOGY
Key clinical point: Epilepsy increases the risk of mortality from unnatural causes.
Major finding: Epilepsy was associated with a significantly increased risk of death from any unnatural cause (HR, 2.8), from accidental medication poisoning (HR, 5.0), and from suicide (HR, 2.2).
Study details: A population-based cohort study of more than 1 million people.
Disclosures: Funders included the National Institute for Health Research and Health and Care Research Wales. The researchers reported having no conflicts of interest.
Source: Gorton HC et al. JAMA Neurol. 2019 Apr 9. doi: 10.1001/jamaneurol.2018.0333.
Social support after Katrina may ease depressive, PTSD symptoms
The availability of social support after a traumatic event such as a natural disaster could help buffer the development of depressive and PTSD symptoms in individuals exposed to the event, according to research published April 5.
In the Journal of Traumatic Stress, researchers reported the results of a survey of 810 adults who were exposed to the third-deadliest hurricane in U.S. history – Hurricane Katrina – in August 2005. Of those adults, 259 were displaced by the hurricane and 546 were not displaced. All of the adults were residents of Mississippi before the hurricane. More than half of the participants were women (52.2%), most were white (73.5%), and their ages ranged from 18 to 91 years.
Interviewers who were supervised by doctoral level clinicians administered numerous self-report questionnaires 18-24 months after the hurricane. Among other measures, the interviews included the Composite International Interview for DSM-IV.
The researchers found a significant negative interaction between perceived social support received in the 2 months after the hurricane and depressive symptoms, both in displaced and nondisplaced individuals.
The study also showed that the number of Katrina-related traumatic events, and whether an individual had been displaced or not, were associated with depressive symptoms – even after accounting for potential confounders, such as the number of previous traumatic events, age, and minority status.
In addition, the study explored the interaction between the number of hurricane-related traumatic events, perceived social support received, and displacement status as predictors of each cluster of PTSD symptoms. Individuals who experienced greater numbers of hurricane-related traumatic events and were displaced by the event showed more reexperiencing, avoidance, and arousal symptoms. However, social support was associated with lower likelihood of all PTSD symptom clusters.
Nondisplaced individuals who experienced a greater number of hurricane-related traumatic events showed higher arousal and avoidance symptoms, but this was only significant in individuals who reported lower levels of social support.
“Unlike previous studies, by controlling for highly correlated variables: number of previous traumatic events experienced and disaster-related stressors,” wrote Adam P. McGuire, PhD, formerly of the University of Mississippi, Jackson, and now at the Veterans Integrated Service Network, and his coauthors.
The authors also commented on the “unexpected” finding that the significant buffering effect of social support was seen both in displaced and nondisplaced residents, “which suggests that perceived social support is linked to important cognitive and behavioral processes that reduce the likelihood of developing depressive symptoms [e.g., challenging negative beliefs about self], and those effects are not limited to nondisplaced disaster survivors.”
The study was supported by the National Institutes of Health and the Midwest Regional Postdoctoral Program in Eating Disorder Research. The authors had no conflicts of interest.
SOURCE: McGuire AP et al. J Trauma Stress. 2018 Apr 5. doi: 10.1002/jts.22270.
The availability of social support after a traumatic event such as a natural disaster could help buffer the development of depressive and PTSD symptoms in individuals exposed to the event, according to research published April 5.
In the Journal of Traumatic Stress, researchers reported the results of a survey of 810 adults who were exposed to the third-deadliest hurricane in U.S. history – Hurricane Katrina – in August 2005. Of those adults, 259 were displaced by the hurricane and 546 were not displaced. All of the adults were residents of Mississippi before the hurricane. More than half of the participants were women (52.2%), most were white (73.5%), and their ages ranged from 18 to 91 years.
Interviewers who were supervised by doctoral level clinicians administered numerous self-report questionnaires 18-24 months after the hurricane. Among other measures, the interviews included the Composite International Interview for DSM-IV.
The researchers found a significant negative interaction between perceived social support received in the 2 months after the hurricane and depressive symptoms, both in displaced and nondisplaced individuals.
The study also showed that the number of Katrina-related traumatic events, and whether an individual had been displaced or not, were associated with depressive symptoms – even after accounting for potential confounders, such as the number of previous traumatic events, age, and minority status.
In addition, the study explored the interaction between the number of hurricane-related traumatic events, perceived social support received, and displacement status as predictors of each cluster of PTSD symptoms. Individuals who experienced greater numbers of hurricane-related traumatic events and were displaced by the event showed more reexperiencing, avoidance, and arousal symptoms. However, social support was associated with lower likelihood of all PTSD symptom clusters.
Nondisplaced individuals who experienced a greater number of hurricane-related traumatic events showed higher arousal and avoidance symptoms, but this was only significant in individuals who reported lower levels of social support.
“Unlike previous studies, by controlling for highly correlated variables: number of previous traumatic events experienced and disaster-related stressors,” wrote Adam P. McGuire, PhD, formerly of the University of Mississippi, Jackson, and now at the Veterans Integrated Service Network, and his coauthors.
The authors also commented on the “unexpected” finding that the significant buffering effect of social support was seen both in displaced and nondisplaced residents, “which suggests that perceived social support is linked to important cognitive and behavioral processes that reduce the likelihood of developing depressive symptoms [e.g., challenging negative beliefs about self], and those effects are not limited to nondisplaced disaster survivors.”
The study was supported by the National Institutes of Health and the Midwest Regional Postdoctoral Program in Eating Disorder Research. The authors had no conflicts of interest.
SOURCE: McGuire AP et al. J Trauma Stress. 2018 Apr 5. doi: 10.1002/jts.22270.
The availability of social support after a traumatic event such as a natural disaster could help buffer the development of depressive and PTSD symptoms in individuals exposed to the event, according to research published April 5.
In the Journal of Traumatic Stress, researchers reported the results of a survey of 810 adults who were exposed to the third-deadliest hurricane in U.S. history – Hurricane Katrina – in August 2005. Of those adults, 259 were displaced by the hurricane and 546 were not displaced. All of the adults were residents of Mississippi before the hurricane. More than half of the participants were women (52.2%), most were white (73.5%), and their ages ranged from 18 to 91 years.
Interviewers who were supervised by doctoral level clinicians administered numerous self-report questionnaires 18-24 months after the hurricane. Among other measures, the interviews included the Composite International Interview for DSM-IV.
The researchers found a significant negative interaction between perceived social support received in the 2 months after the hurricane and depressive symptoms, both in displaced and nondisplaced individuals.
The study also showed that the number of Katrina-related traumatic events, and whether an individual had been displaced or not, were associated with depressive symptoms – even after accounting for potential confounders, such as the number of previous traumatic events, age, and minority status.
In addition, the study explored the interaction between the number of hurricane-related traumatic events, perceived social support received, and displacement status as predictors of each cluster of PTSD symptoms. Individuals who experienced greater numbers of hurricane-related traumatic events and were displaced by the event showed more reexperiencing, avoidance, and arousal symptoms. However, social support was associated with lower likelihood of all PTSD symptom clusters.
Nondisplaced individuals who experienced a greater number of hurricane-related traumatic events showed higher arousal and avoidance symptoms, but this was only significant in individuals who reported lower levels of social support.
“Unlike previous studies, by controlling for highly correlated variables: number of previous traumatic events experienced and disaster-related stressors,” wrote Adam P. McGuire, PhD, formerly of the University of Mississippi, Jackson, and now at the Veterans Integrated Service Network, and his coauthors.
The authors also commented on the “unexpected” finding that the significant buffering effect of social support was seen both in displaced and nondisplaced residents, “which suggests that perceived social support is linked to important cognitive and behavioral processes that reduce the likelihood of developing depressive symptoms [e.g., challenging negative beliefs about self], and those effects are not limited to nondisplaced disaster survivors.”
The study was supported by the National Institutes of Health and the Midwest Regional Postdoctoral Program in Eating Disorder Research. The authors had no conflicts of interest.
SOURCE: McGuire AP et al. J Trauma Stress. 2018 Apr 5. doi: 10.1002/jts.22270.
FROM THE JOURNAL OF TRAUMATIC STRESS
Key clinical point: Social support can reduce the impact of traumatic events such as hurricanes.
Major finding: Perceived social support was associated with reduced depressive symptoms.
Study details: A survey of 810 adults who were exposed to Hurricane Katrina while living in Mississippi.
Disclosures: The study was supported by the National Institutes of Health and the Midwest Regional Postdoctoral Program in Eating Disorder Research. The presenters had no conflicts of interest.
Source: McGuire AP et al. J Trauma Stress. 2018 Apr 5. doi: 10.1002/jts.22270.
Simvastatin, atorvastatin cut mortality risk for sepsis patients
a large health care database review has determined.
Among almost 53,000 sepsis patients, those who had been taking simvastatin were 28% less likely to die within 30 days of a sepsis admission than were patients not taking a statin. Atorvastatin conferred a similar significant survival benefit, reducing the risk of death by 22%, Chien-Chang Lee, MD and his colleagues wrote in the April issue of the journal CHEST®.
The drugs also exert a direct antimicrobial effect, he asserted.
“Of note, simvastatin was shown by several reports to have the most potent antibacterial activity,” targeting both methicillin-resistant and -sensitive Staphylococcus aureus, as well as gram negative and positive bacteria.
Dr. Lee and his colleagues extracted mortality and statin prescription data from the Taiwan National Health Insurance Database from 2000-2011. They looked at 30- and 90-day mortality in 52,737 patients who developed sepsis; the statins of interest were atorvastatin, simvastatin, and rosuvastatin. Patients had to have been taking the medication for at least 30 days before sepsis onset to be included, and patients taking more than one statin were excluded from the analysis.
Patients were a mean of 69 years old. About half had a lower respiratory infection. The remainder had infections within the abdomen, the biliary or urinary tract, skin, or orthopedic infections. There were no significant differences in comorbidities or in other medications taken among the three statin groups or the nonusers.
Of the entire cohort, 17% died by 30 days and nearly 23% by 90 days. Compared with those who had never received a statin, the statin users were 12% less likely to die by 30 days (hazard ratio, 0.88). Mortality at 90 days was also decreased, when compared with nonusers (HR, 0.93).
Simvastatin demonstrated the greatest benefit, with a 28% decreased risk of 30-day mortality (HR, 0.72). Atorvastatin followed, with a 22% risk reduction (HR, 0.78). Rosuvastatin exerted a nonsignificant 13% benefit.
The authors then examined 90-day mortality risks for the patients with a propensity matching score using a subgroup comprising 536 simvastatin users, 536 atorvastatin users, and 536 rosuvastatin users. Simvastatin was associated with a 23% reduction in 30-day mortality risk (HR, 0.77) and atorvastatin with a 21% reduction (HR, 0.79), when compared with rosuvastatin.
Statins’ antimicrobial properties are probably partially caused by their inactivation of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase pathway, Dr. Lee and his colleagues noted. In addition to being vital for cholesterol synthesis, this pathway “also contributes to the production of isoprenoids and lipid compounds that are essential for cell signaling and structure in the pathogen. Secondly, the chemical property of different types of statins may affect their targeting to bacteria. The lipophilic properties of simvastatin or atorvastatin may allow better binding to bacteria cell walls than the hydrophilic properties of rosuvastatin.”
The study was funded by the Taiwan National Science Foundation and Taiwan National Ministry of Science and Technology. Dr. Lee had no financial conflicts.
The statin-sepsis mortality link will probably never be definitively proven, but the study by Lee and colleagues gives us the best data so far on this intriguing connection, Steven Q. Simpson, MD and Joel D. Mermis, MD wrote in an accompanying editorial.
“It is unlikely that prospective randomized trials of statins for prevention of sepsis mortality will ever be undertaken, owing to the sheer number of patients that would require randomization in order to have adequate numbers who actually develop sepsis,” the colleagues wrote. “We believe that the next best thing to randomization and a prospective trial is exactly what the authors have done – identify a cohort, track them through time, even if nonconcurrently, and match cases to controls by propensity matching on important clinical characteristics.”
Nevertheless, the two said, “This brings us to one aspect of the study that leaves open a window for some doubt.”
Lee et al. extracted their data from a large national insurance claims database. These systems “are commonly believed to overestimate sepsis incidence,” Dr. Simpson and Dr. Mermis wrote. A 2009 U.S. study bore this out, they said. “That study showed that in the U.S in 2014, there were approximately 1.7 million cases of sepsis in a population of 330 million, for an annual incidence rate of five sepsis cases per 1,000 patient-years.”
However, a “quick calculation” of the Taiwan data suggests that the annual sepsis caseload is about 5,200 per year in a population of 23 million at risk – an annual incidence of only 0.2 cases per 1,000 patient-years.
“This represents an order of magnitude difference in sepsis incidence between the U.S. and Taiwan, providing some issues to ponder. Does Taiwan indeed have a lower incidence of sepsis by that much? If so, is the lower incidence related to genetics, environment, health care access, or other factors?
“Although Lee et al. have provided us with data of the highest quality that we can likely hope for, the book may not be quite closed, yet.”
Dr. Mermis and Dr. Simpson are pulmonologists at the University of Kansas, Kansas City. They made their comments in an editorial published in the April issue of CHEST® (Mermis JD and Simpson SQ. CHEST. 2018 April. doi: 10.1016/j.chest.2017.12.004.)
The statin-sepsis mortality link will probably never be definitively proven, but the study by Lee and colleagues gives us the best data so far on this intriguing connection, Steven Q. Simpson, MD and Joel D. Mermis, MD wrote in an accompanying editorial.
“It is unlikely that prospective randomized trials of statins for prevention of sepsis mortality will ever be undertaken, owing to the sheer number of patients that would require randomization in order to have adequate numbers who actually develop sepsis,” the colleagues wrote. “We believe that the next best thing to randomization and a prospective trial is exactly what the authors have done – identify a cohort, track them through time, even if nonconcurrently, and match cases to controls by propensity matching on important clinical characteristics.”
Nevertheless, the two said, “This brings us to one aspect of the study that leaves open a window for some doubt.”
Lee et al. extracted their data from a large national insurance claims database. These systems “are commonly believed to overestimate sepsis incidence,” Dr. Simpson and Dr. Mermis wrote. A 2009 U.S. study bore this out, they said. “That study showed that in the U.S in 2014, there were approximately 1.7 million cases of sepsis in a population of 330 million, for an annual incidence rate of five sepsis cases per 1,000 patient-years.”
However, a “quick calculation” of the Taiwan data suggests that the annual sepsis caseload is about 5,200 per year in a population of 23 million at risk – an annual incidence of only 0.2 cases per 1,000 patient-years.
“This represents an order of magnitude difference in sepsis incidence between the U.S. and Taiwan, providing some issues to ponder. Does Taiwan indeed have a lower incidence of sepsis by that much? If so, is the lower incidence related to genetics, environment, health care access, or other factors?
“Although Lee et al. have provided us with data of the highest quality that we can likely hope for, the book may not be quite closed, yet.”
Dr. Mermis and Dr. Simpson are pulmonologists at the University of Kansas, Kansas City. They made their comments in an editorial published in the April issue of CHEST® (Mermis JD and Simpson SQ. CHEST. 2018 April. doi: 10.1016/j.chest.2017.12.004.)
The statin-sepsis mortality link will probably never be definitively proven, but the study by Lee and colleagues gives us the best data so far on this intriguing connection, Steven Q. Simpson, MD and Joel D. Mermis, MD wrote in an accompanying editorial.
“It is unlikely that prospective randomized trials of statins for prevention of sepsis mortality will ever be undertaken, owing to the sheer number of patients that would require randomization in order to have adequate numbers who actually develop sepsis,” the colleagues wrote. “We believe that the next best thing to randomization and a prospective trial is exactly what the authors have done – identify a cohort, track them through time, even if nonconcurrently, and match cases to controls by propensity matching on important clinical characteristics.”
Nevertheless, the two said, “This brings us to one aspect of the study that leaves open a window for some doubt.”
Lee et al. extracted their data from a large national insurance claims database. These systems “are commonly believed to overestimate sepsis incidence,” Dr. Simpson and Dr. Mermis wrote. A 2009 U.S. study bore this out, they said. “That study showed that in the U.S in 2014, there were approximately 1.7 million cases of sepsis in a population of 330 million, for an annual incidence rate of five sepsis cases per 1,000 patient-years.”
However, a “quick calculation” of the Taiwan data suggests that the annual sepsis caseload is about 5,200 per year in a population of 23 million at risk – an annual incidence of only 0.2 cases per 1,000 patient-years.
“This represents an order of magnitude difference in sepsis incidence between the U.S. and Taiwan, providing some issues to ponder. Does Taiwan indeed have a lower incidence of sepsis by that much? If so, is the lower incidence related to genetics, environment, health care access, or other factors?
“Although Lee et al. have provided us with data of the highest quality that we can likely hope for, the book may not be quite closed, yet.”
Dr. Mermis and Dr. Simpson are pulmonologists at the University of Kansas, Kansas City. They made their comments in an editorial published in the April issue of CHEST® (Mermis JD and Simpson SQ. CHEST. 2018 April. doi: 10.1016/j.chest.2017.12.004.)
a large health care database review has determined.
Among almost 53,000 sepsis patients, those who had been taking simvastatin were 28% less likely to die within 30 days of a sepsis admission than were patients not taking a statin. Atorvastatin conferred a similar significant survival benefit, reducing the risk of death by 22%, Chien-Chang Lee, MD and his colleagues wrote in the April issue of the journal CHEST®.
The drugs also exert a direct antimicrobial effect, he asserted.
“Of note, simvastatin was shown by several reports to have the most potent antibacterial activity,” targeting both methicillin-resistant and -sensitive Staphylococcus aureus, as well as gram negative and positive bacteria.
Dr. Lee and his colleagues extracted mortality and statin prescription data from the Taiwan National Health Insurance Database from 2000-2011. They looked at 30- and 90-day mortality in 52,737 patients who developed sepsis; the statins of interest were atorvastatin, simvastatin, and rosuvastatin. Patients had to have been taking the medication for at least 30 days before sepsis onset to be included, and patients taking more than one statin were excluded from the analysis.
Patients were a mean of 69 years old. About half had a lower respiratory infection. The remainder had infections within the abdomen, the biliary or urinary tract, skin, or orthopedic infections. There were no significant differences in comorbidities or in other medications taken among the three statin groups or the nonusers.
Of the entire cohort, 17% died by 30 days and nearly 23% by 90 days. Compared with those who had never received a statin, the statin users were 12% less likely to die by 30 days (hazard ratio, 0.88). Mortality at 90 days was also decreased, when compared with nonusers (HR, 0.93).
Simvastatin demonstrated the greatest benefit, with a 28% decreased risk of 30-day mortality (HR, 0.72). Atorvastatin followed, with a 22% risk reduction (HR, 0.78). Rosuvastatin exerted a nonsignificant 13% benefit.
The authors then examined 90-day mortality risks for the patients with a propensity matching score using a subgroup comprising 536 simvastatin users, 536 atorvastatin users, and 536 rosuvastatin users. Simvastatin was associated with a 23% reduction in 30-day mortality risk (HR, 0.77) and atorvastatin with a 21% reduction (HR, 0.79), when compared with rosuvastatin.
Statins’ antimicrobial properties are probably partially caused by their inactivation of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase pathway, Dr. Lee and his colleagues noted. In addition to being vital for cholesterol synthesis, this pathway “also contributes to the production of isoprenoids and lipid compounds that are essential for cell signaling and structure in the pathogen. Secondly, the chemical property of different types of statins may affect their targeting to bacteria. The lipophilic properties of simvastatin or atorvastatin may allow better binding to bacteria cell walls than the hydrophilic properties of rosuvastatin.”
The study was funded by the Taiwan National Science Foundation and Taiwan National Ministry of Science and Technology. Dr. Lee had no financial conflicts.
a large health care database review has determined.
Among almost 53,000 sepsis patients, those who had been taking simvastatin were 28% less likely to die within 30 days of a sepsis admission than were patients not taking a statin. Atorvastatin conferred a similar significant survival benefit, reducing the risk of death by 22%, Chien-Chang Lee, MD and his colleagues wrote in the April issue of the journal CHEST®.
The drugs also exert a direct antimicrobial effect, he asserted.
“Of note, simvastatin was shown by several reports to have the most potent antibacterial activity,” targeting both methicillin-resistant and -sensitive Staphylococcus aureus, as well as gram negative and positive bacteria.
Dr. Lee and his colleagues extracted mortality and statin prescription data from the Taiwan National Health Insurance Database from 2000-2011. They looked at 30- and 90-day mortality in 52,737 patients who developed sepsis; the statins of interest were atorvastatin, simvastatin, and rosuvastatin. Patients had to have been taking the medication for at least 30 days before sepsis onset to be included, and patients taking more than one statin were excluded from the analysis.
Patients were a mean of 69 years old. About half had a lower respiratory infection. The remainder had infections within the abdomen, the biliary or urinary tract, skin, or orthopedic infections. There were no significant differences in comorbidities or in other medications taken among the three statin groups or the nonusers.
Of the entire cohort, 17% died by 30 days and nearly 23% by 90 days. Compared with those who had never received a statin, the statin users were 12% less likely to die by 30 days (hazard ratio, 0.88). Mortality at 90 days was also decreased, when compared with nonusers (HR, 0.93).
Simvastatin demonstrated the greatest benefit, with a 28% decreased risk of 30-day mortality (HR, 0.72). Atorvastatin followed, with a 22% risk reduction (HR, 0.78). Rosuvastatin exerted a nonsignificant 13% benefit.
The authors then examined 90-day mortality risks for the patients with a propensity matching score using a subgroup comprising 536 simvastatin users, 536 atorvastatin users, and 536 rosuvastatin users. Simvastatin was associated with a 23% reduction in 30-day mortality risk (HR, 0.77) and atorvastatin with a 21% reduction (HR, 0.79), when compared with rosuvastatin.
Statins’ antimicrobial properties are probably partially caused by their inactivation of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase pathway, Dr. Lee and his colleagues noted. In addition to being vital for cholesterol synthesis, this pathway “also contributes to the production of isoprenoids and lipid compounds that are essential for cell signaling and structure in the pathogen. Secondly, the chemical property of different types of statins may affect their targeting to bacteria. The lipophilic properties of simvastatin or atorvastatin may allow better binding to bacteria cell walls than the hydrophilic properties of rosuvastatin.”
The study was funded by the Taiwan National Science Foundation and Taiwan National Ministry of Science and Technology. Dr. Lee had no financial conflicts.
FROM CHEST
Key clinical point: Simvastatin and atorvastatin were associated with decreased mortality risk among sepsis patients.
Major finding: Compared with those not taking the drugs, those taking simvastatin were 28% less likely to die by 30 days, and those taking atorvastatin were 22% less likely.
Study details: The database study comprised almost 54,000 sepsis cases over 11 years.
Disclosures: The study was funded by the Taiwan National Science Foundation and Taiwan National Ministry of Science and Technology. Dr. Lee had no financial conflicts.
Source: Lee C-C et al. CHEST. 2018 April;153(4):769-70.