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Higher hospital mortality in pediatric emergency transfer patients
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
I’ve learned so much this summer from working with Dr. Patrick Brady to better understand characteristics of pediatric patients who undergo clinical deterioration and unplanned transfers to the ICU. I’m very grateful to have spent my summer with a mentor who really cared about my growth as a student, and a fantastic group of physicians in the Division of Hospital Medicine at Cincinnati Children’s Hospital Medical Center.
After data analysis, we discovered that children who have had an emergency transfer event spend a longer time in the ICU and in the hospital. After comparing hospital mortality, we can conclude that emergency transfer patients have a higher likelihood of hospital mortality.
From this preliminary research, the emergency transfer metric in children’s hospitals has the potential to enable more rapid learning and systems improvement. We have a few next steps to investigate these next couple months as well. We want to compare medical diagnoses and complex chronic conditions between the emergency transfer cases and controls. We also hope to describe the incidence using a patient-days denominator. Finally, our long term goals are to identify predictors for an emergency transfer event in children.
Farah Hussain is a 2nd-year medical student at University of Cincinnati College of Medicine and student researcher at Cincinnati Children’s Hospital Medical Center. Her research interests involve bettering patient care to vulnerable populations.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
I’ve learned so much this summer from working with Dr. Patrick Brady to better understand characteristics of pediatric patients who undergo clinical deterioration and unplanned transfers to the ICU. I’m very grateful to have spent my summer with a mentor who really cared about my growth as a student, and a fantastic group of physicians in the Division of Hospital Medicine at Cincinnati Children’s Hospital Medical Center.
After data analysis, we discovered that children who have had an emergency transfer event spend a longer time in the ICU and in the hospital. After comparing hospital mortality, we can conclude that emergency transfer patients have a higher likelihood of hospital mortality.
From this preliminary research, the emergency transfer metric in children’s hospitals has the potential to enable more rapid learning and systems improvement. We have a few next steps to investigate these next couple months as well. We want to compare medical diagnoses and complex chronic conditions between the emergency transfer cases and controls. We also hope to describe the incidence using a patient-days denominator. Finally, our long term goals are to identify predictors for an emergency transfer event in children.
Farah Hussain is a 2nd-year medical student at University of Cincinnati College of Medicine and student researcher at Cincinnati Children’s Hospital Medical Center. Her research interests involve bettering patient care to vulnerable populations.
Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the program, recipients are required to write about their experience on a biweekly basis.
I’ve learned so much this summer from working with Dr. Patrick Brady to better understand characteristics of pediatric patients who undergo clinical deterioration and unplanned transfers to the ICU. I’m very grateful to have spent my summer with a mentor who really cared about my growth as a student, and a fantastic group of physicians in the Division of Hospital Medicine at Cincinnati Children’s Hospital Medical Center.
After data analysis, we discovered that children who have had an emergency transfer event spend a longer time in the ICU and in the hospital. After comparing hospital mortality, we can conclude that emergency transfer patients have a higher likelihood of hospital mortality.
From this preliminary research, the emergency transfer metric in children’s hospitals has the potential to enable more rapid learning and systems improvement. We have a few next steps to investigate these next couple months as well. We want to compare medical diagnoses and complex chronic conditions between the emergency transfer cases and controls. We also hope to describe the incidence using a patient-days denominator. Finally, our long term goals are to identify predictors for an emergency transfer event in children.
Farah Hussain is a 2nd-year medical student at University of Cincinnati College of Medicine and student researcher at Cincinnati Children’s Hospital Medical Center. Her research interests involve bettering patient care to vulnerable populations.
Debate: Is MRD ready for prime time in multiple myeloma?
NEW YORK – Evidence of minimal residual disease (MRD) has been shown to be an important prognostic factor in several different hematologic malignancies, including acute and chronic myeloid leukemias, but its clinical utility in day-to-day practice in multiple myeloma is still uncertain.
At the annual Lymphoma & Myeloma International Congress on Hematologic Malignancies, C. Ola Landgren, MD, PhD, chief of the myeloma service at Memorial Sloan Kettering Cancer Center in New York, and Paul G. Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Myeloma Center at the Dana-Farber Cancer Institute in Boston, debated the question: “Is MRD ready for prime time?”
Yes: Dr. Landgren
“As we all know, with older drugs for myeloma, only a small proportion of patients reached a complete response, so there was really no reason to talk about MRD. But this belongs to the past: using the modern combination therapies, about 100% of our patients have a response, an overall response, and up to 80% of patients are reaching a complete response. So it’s really necessary, a logical step to go forward, to look at MRD,” Dr. Landgren said.
He cited evidence from two meta-analyses showing that MRD negativity is a strong predictor of clinical outcomes, including long-term survival.
“Our results show that MRD negativity is a strong predictor of clinical outcomes, supportive of MRD becoming a regulatory end point for drug approval in newly diagnosed multiple myeloma,” they wrote.
In a second meta-analysis, Nikhil Munshi, MD, from the Dana-Farber Cancer Institute, and his colleagues, reviewed PFS data from 14 studies with a total of 1,273 patients, and OS data from 12 studies with a total of 1,100 patients.
This second meta-analysis found that MRD negativity was associated with significantly better PFS (HR, 0.41; P less than .001), including among patients in studies looking specifically at complete response (CR) (HR, 0.44; P less than .001).
Munshi et al. also saw a significant benefit for MRD negativity among all patients in trials with OS as the endpoint (HR, 0.57; P less than .001) and in those focusing on patients with a CR (HR, 0.47; P less than .001).
They concluded that MRD-negative status after treatment for new newly diagnosed multiple myeloma is associated with long-term survival, and like Landgren et al. contended that their findings “provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of multiple myeloma.”
Dr. Landgren noted that 2016 International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma, coauthored by both Dr. Landgren and Dr. Richardson, now incorporate MRD.
In addition, in the IFM/DFCI 2009 trial comparing induction therapy for patients with newly diagnosed multiple myeloma with or without autologous stem cell transplant after three cycles of lenalidomide, bortezomib, and dexamethasone, patients in each trial arm who were MRD negative had significantly better PFS than patients who were MRD positive after consolidation, regardless of assigned treatment, Dr. Landgren noted.
In the relapsed/refractory multiple myeloma setting, MRD negativity was associated with better PFS for patients in the POLLUX trial, whether subjects were assigned to receive daratumumab plus lenalidomide and dexamethasone, or len-dex alone.
“This raises an important question: Is MRD more important than treatment modality?” Dr. Landgren said.
“The debate is: Is MRD ready for prime time? And as I have shown you with all the data, the answer is ‘Yes’,” he concluded.
No: Dr. Richardson
“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena. The question for me as a clinician in my clinic is: ‘Do I apply it to everyday practice?’ And I would simply suggest to you at this point we’re not ready for that, and we’re not ready for that for a variety of complex reasons,” Dr. Richardson said in his rebuttal.
He cited a definition of MRD offered by Simone Ferrero, MD, and his colleagues from the University of Turin (Italy) in 2011 in Hematological Oncology: “Any approach aimed at detecting and possibly quantifying residual tumor cells beyond the sensitivity level of routine imaging and laboratory techniques.”
“We recognize in hematologic malignancies in particular, and increasingly in myeloma, that achievement of complete clinical remission and assessing this needs a variety of different scenarios,” he said.
These scenarios may include establishing the full eradication of the neoplastic clone, determining the long-term persistence of quiescent or nonclonogenic or immunologically regulated tumor cells, or persistence of clonogenic cells capable of giving rise to a full clinical relapse within a number of years.
Myeloma specialists recognize that MRD is a real phenomenon, made more challenging by the “extraordinary” heterogeneity of myeloma, he said.
Determination of MRD using sensitive molecular techniques may allow analysis of treatments that induce a greater depth of response than others, and may also identify patients who are experiencing early relapse and will need further treatment, Dr. Richardson acknowledged.
“The question is, should it dictate what you and I do every afternoon in the clinic with a particular patient, for example, outside of a clinical trial?”
He noted that MRD is still a secondary endpoint in trials for acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, and chronic lymphocytic leukemia, although it has been accepted by the FDA as a primary endpoint to assess molecular responses to second-generation tyrosine kinase inhibitors.
MRD is also still a secondary endpoint in trials for therapies against follicular and mantle cell lymphomas as well.
“So my hypothesis, or suggestion to you this morning, is that whilst MRD clearly is a vital area of research – and I especially applaud Ola for being on the forefront of this, and I fully support all the points he made – I would just simply suggest to you that it’s less advanced than in leukemia and lymphoma, and we are currently at the point where MRD assessments are clearly secondary endpoints and an important research tool,” he said,
MRD remains a research tool in multiple myeloma because, despite the wealth of new therapies and combinations approved in just the past few years, “we’re not able to eradicate it completely, and cure remains in myeloma, frankly, evasive,” he added.
Immunotherapy, for example, is not the “mutationally agnostic” approach that clinicians had hoped for, with recent evidence suggesting that it cannot overcome every genetic variation that may give rise to multiple myeloma.
For MRD to become a useful clinical tool rather than a research/regulatory tool, standardization of testing methods will be needed. Flow cytometry until recently has been the mainstay for detecting MRD, but molecular strategies are currently being investigated, and rapid next-generation sequencing has the potential to become a gold standard, with its ability to identify and quantify all clonotypes in a sample.
“What’s critical is, therapeutic adjustment for what? What is the difference? For example, [if] one arm of a trial has 20% MRD positivity vs. 40% in another, what does that really mean for overall survival? These are enormous challenges that we still face,” Dr. Richardson said.
“I do think the lack of standardization broadly across the country is a challenge, and so with that in mind, I would simply suggest that it is not yet a standard of care in clinical practice, but may be,” he concluded.
Dr. Landgren disclosed serving as a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene and Janssen. Dr. Richardson disclosed consulting for Celgene and Takeda.
NEW YORK – Evidence of minimal residual disease (MRD) has been shown to be an important prognostic factor in several different hematologic malignancies, including acute and chronic myeloid leukemias, but its clinical utility in day-to-day practice in multiple myeloma is still uncertain.
At the annual Lymphoma & Myeloma International Congress on Hematologic Malignancies, C. Ola Landgren, MD, PhD, chief of the myeloma service at Memorial Sloan Kettering Cancer Center in New York, and Paul G. Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Myeloma Center at the Dana-Farber Cancer Institute in Boston, debated the question: “Is MRD ready for prime time?”
Yes: Dr. Landgren
“As we all know, with older drugs for myeloma, only a small proportion of patients reached a complete response, so there was really no reason to talk about MRD. But this belongs to the past: using the modern combination therapies, about 100% of our patients have a response, an overall response, and up to 80% of patients are reaching a complete response. So it’s really necessary, a logical step to go forward, to look at MRD,” Dr. Landgren said.
He cited evidence from two meta-analyses showing that MRD negativity is a strong predictor of clinical outcomes, including long-term survival.
“Our results show that MRD negativity is a strong predictor of clinical outcomes, supportive of MRD becoming a regulatory end point for drug approval in newly diagnosed multiple myeloma,” they wrote.
In a second meta-analysis, Nikhil Munshi, MD, from the Dana-Farber Cancer Institute, and his colleagues, reviewed PFS data from 14 studies with a total of 1,273 patients, and OS data from 12 studies with a total of 1,100 patients.
This second meta-analysis found that MRD negativity was associated with significantly better PFS (HR, 0.41; P less than .001), including among patients in studies looking specifically at complete response (CR) (HR, 0.44; P less than .001).
Munshi et al. also saw a significant benefit for MRD negativity among all patients in trials with OS as the endpoint (HR, 0.57; P less than .001) and in those focusing on patients with a CR (HR, 0.47; P less than .001).
They concluded that MRD-negative status after treatment for new newly diagnosed multiple myeloma is associated with long-term survival, and like Landgren et al. contended that their findings “provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of multiple myeloma.”
Dr. Landgren noted that 2016 International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma, coauthored by both Dr. Landgren and Dr. Richardson, now incorporate MRD.
In addition, in the IFM/DFCI 2009 trial comparing induction therapy for patients with newly diagnosed multiple myeloma with or without autologous stem cell transplant after three cycles of lenalidomide, bortezomib, and dexamethasone, patients in each trial arm who were MRD negative had significantly better PFS than patients who were MRD positive after consolidation, regardless of assigned treatment, Dr. Landgren noted.
In the relapsed/refractory multiple myeloma setting, MRD negativity was associated with better PFS for patients in the POLLUX trial, whether subjects were assigned to receive daratumumab plus lenalidomide and dexamethasone, or len-dex alone.
“This raises an important question: Is MRD more important than treatment modality?” Dr. Landgren said.
“The debate is: Is MRD ready for prime time? And as I have shown you with all the data, the answer is ‘Yes’,” he concluded.
No: Dr. Richardson
“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena. The question for me as a clinician in my clinic is: ‘Do I apply it to everyday practice?’ And I would simply suggest to you at this point we’re not ready for that, and we’re not ready for that for a variety of complex reasons,” Dr. Richardson said in his rebuttal.
He cited a definition of MRD offered by Simone Ferrero, MD, and his colleagues from the University of Turin (Italy) in 2011 in Hematological Oncology: “Any approach aimed at detecting and possibly quantifying residual tumor cells beyond the sensitivity level of routine imaging and laboratory techniques.”
“We recognize in hematologic malignancies in particular, and increasingly in myeloma, that achievement of complete clinical remission and assessing this needs a variety of different scenarios,” he said.
These scenarios may include establishing the full eradication of the neoplastic clone, determining the long-term persistence of quiescent or nonclonogenic or immunologically regulated tumor cells, or persistence of clonogenic cells capable of giving rise to a full clinical relapse within a number of years.
Myeloma specialists recognize that MRD is a real phenomenon, made more challenging by the “extraordinary” heterogeneity of myeloma, he said.
Determination of MRD using sensitive molecular techniques may allow analysis of treatments that induce a greater depth of response than others, and may also identify patients who are experiencing early relapse and will need further treatment, Dr. Richardson acknowledged.
“The question is, should it dictate what you and I do every afternoon in the clinic with a particular patient, for example, outside of a clinical trial?”
He noted that MRD is still a secondary endpoint in trials for acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, and chronic lymphocytic leukemia, although it has been accepted by the FDA as a primary endpoint to assess molecular responses to second-generation tyrosine kinase inhibitors.
MRD is also still a secondary endpoint in trials for therapies against follicular and mantle cell lymphomas as well.
“So my hypothesis, or suggestion to you this morning, is that whilst MRD clearly is a vital area of research – and I especially applaud Ola for being on the forefront of this, and I fully support all the points he made – I would just simply suggest to you that it’s less advanced than in leukemia and lymphoma, and we are currently at the point where MRD assessments are clearly secondary endpoints and an important research tool,” he said,
MRD remains a research tool in multiple myeloma because, despite the wealth of new therapies and combinations approved in just the past few years, “we’re not able to eradicate it completely, and cure remains in myeloma, frankly, evasive,” he added.
Immunotherapy, for example, is not the “mutationally agnostic” approach that clinicians had hoped for, with recent evidence suggesting that it cannot overcome every genetic variation that may give rise to multiple myeloma.
For MRD to become a useful clinical tool rather than a research/regulatory tool, standardization of testing methods will be needed. Flow cytometry until recently has been the mainstay for detecting MRD, but molecular strategies are currently being investigated, and rapid next-generation sequencing has the potential to become a gold standard, with its ability to identify and quantify all clonotypes in a sample.
“What’s critical is, therapeutic adjustment for what? What is the difference? For example, [if] one arm of a trial has 20% MRD positivity vs. 40% in another, what does that really mean for overall survival? These are enormous challenges that we still face,” Dr. Richardson said.
“I do think the lack of standardization broadly across the country is a challenge, and so with that in mind, I would simply suggest that it is not yet a standard of care in clinical practice, but may be,” he concluded.
Dr. Landgren disclosed serving as a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene and Janssen. Dr. Richardson disclosed consulting for Celgene and Takeda.
NEW YORK – Evidence of minimal residual disease (MRD) has been shown to be an important prognostic factor in several different hematologic malignancies, including acute and chronic myeloid leukemias, but its clinical utility in day-to-day practice in multiple myeloma is still uncertain.
At the annual Lymphoma & Myeloma International Congress on Hematologic Malignancies, C. Ola Landgren, MD, PhD, chief of the myeloma service at Memorial Sloan Kettering Cancer Center in New York, and Paul G. Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Myeloma Center at the Dana-Farber Cancer Institute in Boston, debated the question: “Is MRD ready for prime time?”
Yes: Dr. Landgren
“As we all know, with older drugs for myeloma, only a small proportion of patients reached a complete response, so there was really no reason to talk about MRD. But this belongs to the past: using the modern combination therapies, about 100% of our patients have a response, an overall response, and up to 80% of patients are reaching a complete response. So it’s really necessary, a logical step to go forward, to look at MRD,” Dr. Landgren said.
He cited evidence from two meta-analyses showing that MRD negativity is a strong predictor of clinical outcomes, including long-term survival.
“Our results show that MRD negativity is a strong predictor of clinical outcomes, supportive of MRD becoming a regulatory end point for drug approval in newly diagnosed multiple myeloma,” they wrote.
In a second meta-analysis, Nikhil Munshi, MD, from the Dana-Farber Cancer Institute, and his colleagues, reviewed PFS data from 14 studies with a total of 1,273 patients, and OS data from 12 studies with a total of 1,100 patients.
This second meta-analysis found that MRD negativity was associated with significantly better PFS (HR, 0.41; P less than .001), including among patients in studies looking specifically at complete response (CR) (HR, 0.44; P less than .001).
Munshi et al. also saw a significant benefit for MRD negativity among all patients in trials with OS as the endpoint (HR, 0.57; P less than .001) and in those focusing on patients with a CR (HR, 0.47; P less than .001).
They concluded that MRD-negative status after treatment for new newly diagnosed multiple myeloma is associated with long-term survival, and like Landgren et al. contended that their findings “provide quantitative evidence to support the integration of MRD assessment as an end point in clinical trials of multiple myeloma.”
Dr. Landgren noted that 2016 International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma, coauthored by both Dr. Landgren and Dr. Richardson, now incorporate MRD.
In addition, in the IFM/DFCI 2009 trial comparing induction therapy for patients with newly diagnosed multiple myeloma with or without autologous stem cell transplant after three cycles of lenalidomide, bortezomib, and dexamethasone, patients in each trial arm who were MRD negative had significantly better PFS than patients who were MRD positive after consolidation, regardless of assigned treatment, Dr. Landgren noted.
In the relapsed/refractory multiple myeloma setting, MRD negativity was associated with better PFS for patients in the POLLUX trial, whether subjects were assigned to receive daratumumab plus lenalidomide and dexamethasone, or len-dex alone.
“This raises an important question: Is MRD more important than treatment modality?” Dr. Landgren said.
“The debate is: Is MRD ready for prime time? And as I have shown you with all the data, the answer is ‘Yes’,” he concluded.
No: Dr. Richardson
“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena. The question for me as a clinician in my clinic is: ‘Do I apply it to everyday practice?’ And I would simply suggest to you at this point we’re not ready for that, and we’re not ready for that for a variety of complex reasons,” Dr. Richardson said in his rebuttal.
He cited a definition of MRD offered by Simone Ferrero, MD, and his colleagues from the University of Turin (Italy) in 2011 in Hematological Oncology: “Any approach aimed at detecting and possibly quantifying residual tumor cells beyond the sensitivity level of routine imaging and laboratory techniques.”
“We recognize in hematologic malignancies in particular, and increasingly in myeloma, that achievement of complete clinical remission and assessing this needs a variety of different scenarios,” he said.
These scenarios may include establishing the full eradication of the neoplastic clone, determining the long-term persistence of quiescent or nonclonogenic or immunologically regulated tumor cells, or persistence of clonogenic cells capable of giving rise to a full clinical relapse within a number of years.
Myeloma specialists recognize that MRD is a real phenomenon, made more challenging by the “extraordinary” heterogeneity of myeloma, he said.
Determination of MRD using sensitive molecular techniques may allow analysis of treatments that induce a greater depth of response than others, and may also identify patients who are experiencing early relapse and will need further treatment, Dr. Richardson acknowledged.
“The question is, should it dictate what you and I do every afternoon in the clinic with a particular patient, for example, outside of a clinical trial?”
He noted that MRD is still a secondary endpoint in trials for acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, and chronic lymphocytic leukemia, although it has been accepted by the FDA as a primary endpoint to assess molecular responses to second-generation tyrosine kinase inhibitors.
MRD is also still a secondary endpoint in trials for therapies against follicular and mantle cell lymphomas as well.
“So my hypothesis, or suggestion to you this morning, is that whilst MRD clearly is a vital area of research – and I especially applaud Ola for being on the forefront of this, and I fully support all the points he made – I would just simply suggest to you that it’s less advanced than in leukemia and lymphoma, and we are currently at the point where MRD assessments are clearly secondary endpoints and an important research tool,” he said,
MRD remains a research tool in multiple myeloma because, despite the wealth of new therapies and combinations approved in just the past few years, “we’re not able to eradicate it completely, and cure remains in myeloma, frankly, evasive,” he added.
Immunotherapy, for example, is not the “mutationally agnostic” approach that clinicians had hoped for, with recent evidence suggesting that it cannot overcome every genetic variation that may give rise to multiple myeloma.
For MRD to become a useful clinical tool rather than a research/regulatory tool, standardization of testing methods will be needed. Flow cytometry until recently has been the mainstay for detecting MRD, but molecular strategies are currently being investigated, and rapid next-generation sequencing has the potential to become a gold standard, with its ability to identify and quantify all clonotypes in a sample.
“What’s critical is, therapeutic adjustment for what? What is the difference? For example, [if] one arm of a trial has 20% MRD positivity vs. 40% in another, what does that really mean for overall survival? These are enormous challenges that we still face,” Dr. Richardson said.
“I do think the lack of standardization broadly across the country is a challenge, and so with that in mind, I would simply suggest that it is not yet a standard of care in clinical practice, but may be,” he concluded.
Dr. Landgren disclosed serving as a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene and Janssen. Dr. Richardson disclosed consulting for Celgene and Takeda.
AT LYMPHOMA & MYELOMA 2017
Elderly patients’ view and the discussion of discontinuing cancer screening
Clinical question: How do elderly patients feel about discontinuing cancer screening, and how should their doctors communicate this topic to them?
Background: Subjecting patients with limited life expectancy to cancer screening can cause harm, but patient preference on the subject and the manner physicians communicate this recommendation is unknown.
Setting: Four programs associated with an urban academic center.
Synopsis: Through interviews, questionnaires, and medical records of 40 community-dwelling adults, over the age of 65, the study found that participants support discontinuing cancer screening based on individual health status. Participants preferred that physicians use health and functional status rather than risks and benefits of test or life expectancy. They do not understand the predictors of life expectancy, are doubtful of physicians’ ability to predict it, and feel discussing it is depressing. While participants were divided on whether the term “life expectancy” should be used, they preferred “this test will not extend your life” to “you may not live long enough to benefit from this test.”
The study is limited to one center with participants with high levels of trust in their established physician which may not reflect other patients. The study required self-reporting and thus is susceptible to recall bias. Decisions of hypothetical examples could be discordant with actual decisions a participant might make.
Bottom line: Elderly patients are amenable to stopping cancer screening when communicated by their established physician and prefer to not discuss life expectancy.
Citation: Schoenborn NL, Lee K, Pollack CE, et.al. Older adults’ views and communication preferences about cancer screening and cessation. JAMA Intern Med. 2017; 2017 Jun 12. doi: 10.1001/jamainternmed.2017.1778.
Dr. Kochar is hospitalist and assistant professor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: How do elderly patients feel about discontinuing cancer screening, and how should their doctors communicate this topic to them?
Background: Subjecting patients with limited life expectancy to cancer screening can cause harm, but patient preference on the subject and the manner physicians communicate this recommendation is unknown.
Setting: Four programs associated with an urban academic center.
Synopsis: Through interviews, questionnaires, and medical records of 40 community-dwelling adults, over the age of 65, the study found that participants support discontinuing cancer screening based on individual health status. Participants preferred that physicians use health and functional status rather than risks and benefits of test or life expectancy. They do not understand the predictors of life expectancy, are doubtful of physicians’ ability to predict it, and feel discussing it is depressing. While participants were divided on whether the term “life expectancy” should be used, they preferred “this test will not extend your life” to “you may not live long enough to benefit from this test.”
The study is limited to one center with participants with high levels of trust in their established physician which may not reflect other patients. The study required self-reporting and thus is susceptible to recall bias. Decisions of hypothetical examples could be discordant with actual decisions a participant might make.
Bottom line: Elderly patients are amenable to stopping cancer screening when communicated by their established physician and prefer to not discuss life expectancy.
Citation: Schoenborn NL, Lee K, Pollack CE, et.al. Older adults’ views and communication preferences about cancer screening and cessation. JAMA Intern Med. 2017; 2017 Jun 12. doi: 10.1001/jamainternmed.2017.1778.
Dr. Kochar is hospitalist and assistant professor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
Clinical question: How do elderly patients feel about discontinuing cancer screening, and how should their doctors communicate this topic to them?
Background: Subjecting patients with limited life expectancy to cancer screening can cause harm, but patient preference on the subject and the manner physicians communicate this recommendation is unknown.
Setting: Four programs associated with an urban academic center.
Synopsis: Through interviews, questionnaires, and medical records of 40 community-dwelling adults, over the age of 65, the study found that participants support discontinuing cancer screening based on individual health status. Participants preferred that physicians use health and functional status rather than risks and benefits of test or life expectancy. They do not understand the predictors of life expectancy, are doubtful of physicians’ ability to predict it, and feel discussing it is depressing. While participants were divided on whether the term “life expectancy” should be used, they preferred “this test will not extend your life” to “you may not live long enough to benefit from this test.”
The study is limited to one center with participants with high levels of trust in their established physician which may not reflect other patients. The study required self-reporting and thus is susceptible to recall bias. Decisions of hypothetical examples could be discordant with actual decisions a participant might make.
Bottom line: Elderly patients are amenable to stopping cancer screening when communicated by their established physician and prefer to not discuss life expectancy.
Citation: Schoenborn NL, Lee K, Pollack CE, et.al. Older adults’ views and communication preferences about cancer screening and cessation. JAMA Intern Med. 2017; 2017 Jun 12. doi: 10.1001/jamainternmed.2017.1778.
Dr. Kochar is hospitalist and assistant professor of medicine, Icahn School of Medicine of the Mount Sinai Health System.
NCI-MATCH: Nivolumab shows promising activity in noncolorectal cancers
NATIONAL HARBOR, MD. – The immune checkpoint inhibitor nivolumab has promising activity in mismatch repair–deficient noncolorectal cancers, according to preliminary findings from the first sub-arm of the National Cancer Institute’s landmark Molecular Analysis for Therapy Choice (NCI-MATCH) trial.
NCI-MATCH is a 1,173-site precision medicine trial launched in 2015 to study targeted therapies for patients with relapsed/refractory solid tumors, lymphomas, and myelomas. In the first substudy (arm Z1D), the investigators identified 4,900 subjects with samples that could be tested for “actionable molecular abnormalities,” and from among those, they identified 77 with loss of mismatch repair proteins MLH1 or MSH2. Ultimately 47 patients were treated with nivolumab in the substudy.
The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease, said Dr. Azad of Johns Hopkins University, Baltimore.
The patients had a median age of 60 years and were heavily pretreated with a median of three prior therapies. The most common histologies among them were endometrioid endometrial cancer (10 patients), prostate cancer (6 patients), and breast cancer (3 patients).
The safety and tolerability of treatment was as expected for single-agent nivolumab treatment. Toxicity was predominantly low-grade fatigue. Anemia was the most common grade 3 toxicity.
“DNA repair defects due to mismatch repair–deficiency are most commonly caused by silencing of mismatch repair proteins MLH1 or MSH2 and, a little less commonly, MSH6 or PMS2. This can happen through DNA mutation, as well as promoter methylation,” Dr. Azad explained. “In fact, nivolumab has already been tested in patients with mismatch repair–deficient colorectal cancer, both alone and in combination with anti-CTLA-4 ipilimumab ... in addition, pembrolizumab was approved earlier this year for pretreated mismatch repair–deficient cancer.”
“So this formed the nidus for our interest and hypothesis that nivolumab would also have activity in mismatch repair–deficient noncolorectal cancer,” she said.
Study subjects had relapsed/refractory cancers, good end-organ function, and good performance status. They were screened for molecular alterations by centralized testing on fresh biopsy tissue, and mismatch repair deficiency was defined through immunohistochemistry as loss of nuclear expression of MLH1 or MSH2. Patients with mismatch repair–deficient colorectal cancer were excluded.
Those in the nivolumab arm received 3 mg/kg every 2 weeks, and after cycle 4, they could be switched to receive treatment every 4 weeks. Imaging was performed every 2 weeks, and patients were allowed to remain in the study as long as their disease had not progressed. A caveat was that patients with progression within the first 24 weeks, but with no more than four new lesions or 40% increase in tumor index lesions, could remain in the study as long as they were clinically stable.
The overall response rate was compared against a null value of 5%.
“We enrolled 35 patients so that we could have 31 evaluable patients, looking for a signal of 5 or greater responses in that patient group to conclude that the arm was promising and worth further testing,” Dr. Azad said. “This gave us 91.8% power to conclude that an agent was promising if the overall response was truly 25%.”
The study met its primary endpoint, with 8 responses out of 34 evaluable patients, she reported.
“Of note, we had five more patients that had unconfirmed responses. Two of those remained on study at the time of data cutoff, so these response numbers may change as the study matures,” she said.
The disease control rate was 56%, and benefit was seen across tumor histologies, she noted.
“The duration of benefit was compelling for these patients,” she said. “The median time to response was 2.1 cycles, and the 6-month progression-free survival was 49%.”
The median duration of response has not been reached.
Follow-up is ongoing, and 12 patients are enrolled in an expansion cohort; results should be reported within the next year.
“Future work includes interrogating tumor tissue and blood to identify possible predictive markers of response and resistance,” Dr. Azad concluded.
Dr. Azad reported having no disclosures.
NATIONAL HARBOR, MD. – The immune checkpoint inhibitor nivolumab has promising activity in mismatch repair–deficient noncolorectal cancers, according to preliminary findings from the first sub-arm of the National Cancer Institute’s landmark Molecular Analysis for Therapy Choice (NCI-MATCH) trial.
NCI-MATCH is a 1,173-site precision medicine trial launched in 2015 to study targeted therapies for patients with relapsed/refractory solid tumors, lymphomas, and myelomas. In the first substudy (arm Z1D), the investigators identified 4,900 subjects with samples that could be tested for “actionable molecular abnormalities,” and from among those, they identified 77 with loss of mismatch repair proteins MLH1 or MSH2. Ultimately 47 patients were treated with nivolumab in the substudy.
The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease, said Dr. Azad of Johns Hopkins University, Baltimore.
The patients had a median age of 60 years and were heavily pretreated with a median of three prior therapies. The most common histologies among them were endometrioid endometrial cancer (10 patients), prostate cancer (6 patients), and breast cancer (3 patients).
The safety and tolerability of treatment was as expected for single-agent nivolumab treatment. Toxicity was predominantly low-grade fatigue. Anemia was the most common grade 3 toxicity.
“DNA repair defects due to mismatch repair–deficiency are most commonly caused by silencing of mismatch repair proteins MLH1 or MSH2 and, a little less commonly, MSH6 or PMS2. This can happen through DNA mutation, as well as promoter methylation,” Dr. Azad explained. “In fact, nivolumab has already been tested in patients with mismatch repair–deficient colorectal cancer, both alone and in combination with anti-CTLA-4 ipilimumab ... in addition, pembrolizumab was approved earlier this year for pretreated mismatch repair–deficient cancer.”
“So this formed the nidus for our interest and hypothesis that nivolumab would also have activity in mismatch repair–deficient noncolorectal cancer,” she said.
Study subjects had relapsed/refractory cancers, good end-organ function, and good performance status. They were screened for molecular alterations by centralized testing on fresh biopsy tissue, and mismatch repair deficiency was defined through immunohistochemistry as loss of nuclear expression of MLH1 or MSH2. Patients with mismatch repair–deficient colorectal cancer were excluded.
Those in the nivolumab arm received 3 mg/kg every 2 weeks, and after cycle 4, they could be switched to receive treatment every 4 weeks. Imaging was performed every 2 weeks, and patients were allowed to remain in the study as long as their disease had not progressed. A caveat was that patients with progression within the first 24 weeks, but with no more than four new lesions or 40% increase in tumor index lesions, could remain in the study as long as they were clinically stable.
The overall response rate was compared against a null value of 5%.
“We enrolled 35 patients so that we could have 31 evaluable patients, looking for a signal of 5 or greater responses in that patient group to conclude that the arm was promising and worth further testing,” Dr. Azad said. “This gave us 91.8% power to conclude that an agent was promising if the overall response was truly 25%.”
The study met its primary endpoint, with 8 responses out of 34 evaluable patients, she reported.
“Of note, we had five more patients that had unconfirmed responses. Two of those remained on study at the time of data cutoff, so these response numbers may change as the study matures,” she said.
The disease control rate was 56%, and benefit was seen across tumor histologies, she noted.
“The duration of benefit was compelling for these patients,” she said. “The median time to response was 2.1 cycles, and the 6-month progression-free survival was 49%.”
The median duration of response has not been reached.
Follow-up is ongoing, and 12 patients are enrolled in an expansion cohort; results should be reported within the next year.
“Future work includes interrogating tumor tissue and blood to identify possible predictive markers of response and resistance,” Dr. Azad concluded.
Dr. Azad reported having no disclosures.
NATIONAL HARBOR, MD. – The immune checkpoint inhibitor nivolumab has promising activity in mismatch repair–deficient noncolorectal cancers, according to preliminary findings from the first sub-arm of the National Cancer Institute’s landmark Molecular Analysis for Therapy Choice (NCI-MATCH) trial.
NCI-MATCH is a 1,173-site precision medicine trial launched in 2015 to study targeted therapies for patients with relapsed/refractory solid tumors, lymphomas, and myelomas. In the first substudy (arm Z1D), the investigators identified 4,900 subjects with samples that could be tested for “actionable molecular abnormalities,” and from among those, they identified 77 with loss of mismatch repair proteins MLH1 or MSH2. Ultimately 47 patients were treated with nivolumab in the substudy.
The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease, said Dr. Azad of Johns Hopkins University, Baltimore.
The patients had a median age of 60 years and were heavily pretreated with a median of three prior therapies. The most common histologies among them were endometrioid endometrial cancer (10 patients), prostate cancer (6 patients), and breast cancer (3 patients).
The safety and tolerability of treatment was as expected for single-agent nivolumab treatment. Toxicity was predominantly low-grade fatigue. Anemia was the most common grade 3 toxicity.
“DNA repair defects due to mismatch repair–deficiency are most commonly caused by silencing of mismatch repair proteins MLH1 or MSH2 and, a little less commonly, MSH6 or PMS2. This can happen through DNA mutation, as well as promoter methylation,” Dr. Azad explained. “In fact, nivolumab has already been tested in patients with mismatch repair–deficient colorectal cancer, both alone and in combination with anti-CTLA-4 ipilimumab ... in addition, pembrolizumab was approved earlier this year for pretreated mismatch repair–deficient cancer.”
“So this formed the nidus for our interest and hypothesis that nivolumab would also have activity in mismatch repair–deficient noncolorectal cancer,” she said.
Study subjects had relapsed/refractory cancers, good end-organ function, and good performance status. They were screened for molecular alterations by centralized testing on fresh biopsy tissue, and mismatch repair deficiency was defined through immunohistochemistry as loss of nuclear expression of MLH1 or MSH2. Patients with mismatch repair–deficient colorectal cancer were excluded.
Those in the nivolumab arm received 3 mg/kg every 2 weeks, and after cycle 4, they could be switched to receive treatment every 4 weeks. Imaging was performed every 2 weeks, and patients were allowed to remain in the study as long as their disease had not progressed. A caveat was that patients with progression within the first 24 weeks, but with no more than four new lesions or 40% increase in tumor index lesions, could remain in the study as long as they were clinically stable.
The overall response rate was compared against a null value of 5%.
“We enrolled 35 patients so that we could have 31 evaluable patients, looking for a signal of 5 or greater responses in that patient group to conclude that the arm was promising and worth further testing,” Dr. Azad said. “This gave us 91.8% power to conclude that an agent was promising if the overall response was truly 25%.”
The study met its primary endpoint, with 8 responses out of 34 evaluable patients, she reported.
“Of note, we had five more patients that had unconfirmed responses. Two of those remained on study at the time of data cutoff, so these response numbers may change as the study matures,” she said.
The disease control rate was 56%, and benefit was seen across tumor histologies, she noted.
“The duration of benefit was compelling for these patients,” she said. “The median time to response was 2.1 cycles, and the 6-month progression-free survival was 49%.”
The median duration of response has not been reached.
Follow-up is ongoing, and 12 patients are enrolled in an expansion cohort; results should be reported within the next year.
“Future work includes interrogating tumor tissue and blood to identify possible predictive markers of response and resistance,” Dr. Azad concluded.
Dr. Azad reported having no disclosures.
AT SITC 2017
Key clinical point:
Major finding: The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease.
Data source: Arm Z1D (35 patients) of the NCI-MATCH trial.
Disclosures: Dr. Azad reported having no disclosures.
Healing chronic venous ulcers? Compression, compression, compression
ESTES PARK, COLO. – Meg A. Lemon, MD, said at a conference on internal medicine sponsored by the University of Colorado at Denver, Aurora.
“The top nine ways of treating venous leg ulcers are compression,” explained Dr. Lemon, a Denver-area dermatologist in private practice. “You generally don’t have an active patient who’s moving around [and] allowing the calf to squeeze venous blood back into the circulation, so you have to compress externally. I spend a lot of time with patients saying, ‘If we don’t wear the compression stockings and we don’t elevate the legs, the wound will never heal.’ ”
Compression stockings are no longer frumpy – they have gotten hip. Endurance athletes have embraced them as a recovery aid, and they now come in a multitude of colorful styles. It’s best to start patients off at 15-20 mm Hg of compression so they don’t get discouraged by the initial challenges of getting the stockings on and off, Dr. Lemon explained, then work up to at least 30 mm Hg. Application devices that function much like a shoehorn can assist patients in getting the stockings on if they report difficulties.
As soon as patients get out of bed in the morning, their venous pressure skyrockets, and inflammatory compounds start accumulating in their legs: “I tell patients they need to put the stockings on before getting out of bed to pee in the morning,” the dermatologist said.
A meta-analysis has shown that adequate compression, coupled with wound debridement when indicated, resulted in the healing of 57% of longstanding chronic venous lower-extremity ulcers within 10 weeks and of 75% within 16 weeks, she reported.
Elevating the legs has therapeutic benefit as well, but it has to be done right. The legs must be above the heart for hours at a time, such as while sleeping or while laying on a couch to read or watch television. Putting three bed pillows under the entire calf – rather than under the feet – does the job. Simply sticking the pillows under the feet can result in painful knee hyperextension, which can lead to poor compliance.
“We’re all basically large columns of fluid,” Dr. Lemon said. “We stand around or sit all the time, and the fluid pools in our legs because the valves in the veins stop closing properly as we age. The increased pressure in the vein causes the vein to leak inflammatory compounds into the surrounding tissue, producing edema and chronic inflammation. The chronicity of the disease leads to really profound changes in the skin that are extraordinarily helpful diagnostically.”
Diagnostic tips
These cutaneous changes include a dark brown discoloration – reminiscent of rust – because of deposition of hemosiderin in tissues. The skin becomes fibrous, hard, and ulcerated. The end stage of chronic venous insufficiency is lipodermatosclerosis, in which the skin becomes almost immobile and the lower leg takes on a champagne bottle shape because of hardening of the skin close to the ankle.
Venography, long preferred in definitively diagnosing venous lower-extremity ulcers, is giving way to venous duplex ultrasound, which is not quite as accurate but spares patients the pain associated with the older procedure.
Roughly 70% of chronic lower-extremity ulcers are of venous origin, Dr. Lemon noted.
She encounters quite a few patients who are hospitalized for what is mistakenly diagnosed as bilateral cellulitis, when their true problem is chronic venous insufficiency. The patient’s response to two questions makes it easy to differentiate the two disorders. One is, “Do your legs hurt more or itch more?”
“If the legs itch more, the patient doesn’t have cellulitis,” Dr. Lemon explained. “Cellulitis doesn’t itch. Also, ask the patient, ‘When did your legs last look normal?’ They usually say it was years ago. That’s not bilateral cellulitis – an acute problem requiring hospitalization. It’s a chronic problem requiring extensive chronic wound care.”
If the lower leg wound site looks like cellulitis, with redness, swelling, and warmth to touch, but it itches rather than hurts, she noted, it’s probably stasis dermatitis, which is very common in patients with venous lower-extremity ulcers. The treatment is a potent topical steroid.
“Don’t be afraid of potent steroids,” Dr. Lemon said. “There is so much inflammation in those tissues, they need a potent steroid on the leg. I usually prescribe fluocinonide 0.05% because it’s reliably beneficial.”
An exudative venous wound should receive a moist dressing.
“Forget what your granny told you, and stop telling patients their wounds need to breathe,” she cautioned. “Wounds generally need to be suffocated and covered with an ointment like Vaseline. A dry wound heals about six times slower than a moist one; that’s been extensively studied in the dermatology, surgery, and burn literature.”
If, after 5-6 months of Dr. Lemon’s efforts, a patient’s wound still isn’t healing, the dermatologist will obtain a venous surgical consultation. In some reported series, surgical treatment of insufficiency – venous stripping – has resulted in improved healing time and fewer recurrent ulcers.
Dr. Lemon reported having no financial conflicts regarding her presentation.
ESTES PARK, COLO. – Meg A. Lemon, MD, said at a conference on internal medicine sponsored by the University of Colorado at Denver, Aurora.
“The top nine ways of treating venous leg ulcers are compression,” explained Dr. Lemon, a Denver-area dermatologist in private practice. “You generally don’t have an active patient who’s moving around [and] allowing the calf to squeeze venous blood back into the circulation, so you have to compress externally. I spend a lot of time with patients saying, ‘If we don’t wear the compression stockings and we don’t elevate the legs, the wound will never heal.’ ”
Compression stockings are no longer frumpy – they have gotten hip. Endurance athletes have embraced them as a recovery aid, and they now come in a multitude of colorful styles. It’s best to start patients off at 15-20 mm Hg of compression so they don’t get discouraged by the initial challenges of getting the stockings on and off, Dr. Lemon explained, then work up to at least 30 mm Hg. Application devices that function much like a shoehorn can assist patients in getting the stockings on if they report difficulties.
As soon as patients get out of bed in the morning, their venous pressure skyrockets, and inflammatory compounds start accumulating in their legs: “I tell patients they need to put the stockings on before getting out of bed to pee in the morning,” the dermatologist said.
A meta-analysis has shown that adequate compression, coupled with wound debridement when indicated, resulted in the healing of 57% of longstanding chronic venous lower-extremity ulcers within 10 weeks and of 75% within 16 weeks, she reported.
Elevating the legs has therapeutic benefit as well, but it has to be done right. The legs must be above the heart for hours at a time, such as while sleeping or while laying on a couch to read or watch television. Putting three bed pillows under the entire calf – rather than under the feet – does the job. Simply sticking the pillows under the feet can result in painful knee hyperextension, which can lead to poor compliance.
“We’re all basically large columns of fluid,” Dr. Lemon said. “We stand around or sit all the time, and the fluid pools in our legs because the valves in the veins stop closing properly as we age. The increased pressure in the vein causes the vein to leak inflammatory compounds into the surrounding tissue, producing edema and chronic inflammation. The chronicity of the disease leads to really profound changes in the skin that are extraordinarily helpful diagnostically.”
Diagnostic tips
These cutaneous changes include a dark brown discoloration – reminiscent of rust – because of deposition of hemosiderin in tissues. The skin becomes fibrous, hard, and ulcerated. The end stage of chronic venous insufficiency is lipodermatosclerosis, in which the skin becomes almost immobile and the lower leg takes on a champagne bottle shape because of hardening of the skin close to the ankle.
Venography, long preferred in definitively diagnosing venous lower-extremity ulcers, is giving way to venous duplex ultrasound, which is not quite as accurate but spares patients the pain associated with the older procedure.
Roughly 70% of chronic lower-extremity ulcers are of venous origin, Dr. Lemon noted.
She encounters quite a few patients who are hospitalized for what is mistakenly diagnosed as bilateral cellulitis, when their true problem is chronic venous insufficiency. The patient’s response to two questions makes it easy to differentiate the two disorders. One is, “Do your legs hurt more or itch more?”
“If the legs itch more, the patient doesn’t have cellulitis,” Dr. Lemon explained. “Cellulitis doesn’t itch. Also, ask the patient, ‘When did your legs last look normal?’ They usually say it was years ago. That’s not bilateral cellulitis – an acute problem requiring hospitalization. It’s a chronic problem requiring extensive chronic wound care.”
If the lower leg wound site looks like cellulitis, with redness, swelling, and warmth to touch, but it itches rather than hurts, she noted, it’s probably stasis dermatitis, which is very common in patients with venous lower-extremity ulcers. The treatment is a potent topical steroid.
“Don’t be afraid of potent steroids,” Dr. Lemon said. “There is so much inflammation in those tissues, they need a potent steroid on the leg. I usually prescribe fluocinonide 0.05% because it’s reliably beneficial.”
An exudative venous wound should receive a moist dressing.
“Forget what your granny told you, and stop telling patients their wounds need to breathe,” she cautioned. “Wounds generally need to be suffocated and covered with an ointment like Vaseline. A dry wound heals about six times slower than a moist one; that’s been extensively studied in the dermatology, surgery, and burn literature.”
If, after 5-6 months of Dr. Lemon’s efforts, a patient’s wound still isn’t healing, the dermatologist will obtain a venous surgical consultation. In some reported series, surgical treatment of insufficiency – venous stripping – has resulted in improved healing time and fewer recurrent ulcers.
Dr. Lemon reported having no financial conflicts regarding her presentation.
ESTES PARK, COLO. – Meg A. Lemon, MD, said at a conference on internal medicine sponsored by the University of Colorado at Denver, Aurora.
“The top nine ways of treating venous leg ulcers are compression,” explained Dr. Lemon, a Denver-area dermatologist in private practice. “You generally don’t have an active patient who’s moving around [and] allowing the calf to squeeze venous blood back into the circulation, so you have to compress externally. I spend a lot of time with patients saying, ‘If we don’t wear the compression stockings and we don’t elevate the legs, the wound will never heal.’ ”
Compression stockings are no longer frumpy – they have gotten hip. Endurance athletes have embraced them as a recovery aid, and they now come in a multitude of colorful styles. It’s best to start patients off at 15-20 mm Hg of compression so they don’t get discouraged by the initial challenges of getting the stockings on and off, Dr. Lemon explained, then work up to at least 30 mm Hg. Application devices that function much like a shoehorn can assist patients in getting the stockings on if they report difficulties.
As soon as patients get out of bed in the morning, their venous pressure skyrockets, and inflammatory compounds start accumulating in their legs: “I tell patients they need to put the stockings on before getting out of bed to pee in the morning,” the dermatologist said.
A meta-analysis has shown that adequate compression, coupled with wound debridement when indicated, resulted in the healing of 57% of longstanding chronic venous lower-extremity ulcers within 10 weeks and of 75% within 16 weeks, she reported.
Elevating the legs has therapeutic benefit as well, but it has to be done right. The legs must be above the heart for hours at a time, such as while sleeping or while laying on a couch to read or watch television. Putting three bed pillows under the entire calf – rather than under the feet – does the job. Simply sticking the pillows under the feet can result in painful knee hyperextension, which can lead to poor compliance.
“We’re all basically large columns of fluid,” Dr. Lemon said. “We stand around or sit all the time, and the fluid pools in our legs because the valves in the veins stop closing properly as we age. The increased pressure in the vein causes the vein to leak inflammatory compounds into the surrounding tissue, producing edema and chronic inflammation. The chronicity of the disease leads to really profound changes in the skin that are extraordinarily helpful diagnostically.”
Diagnostic tips
These cutaneous changes include a dark brown discoloration – reminiscent of rust – because of deposition of hemosiderin in tissues. The skin becomes fibrous, hard, and ulcerated. The end stage of chronic venous insufficiency is lipodermatosclerosis, in which the skin becomes almost immobile and the lower leg takes on a champagne bottle shape because of hardening of the skin close to the ankle.
Venography, long preferred in definitively diagnosing venous lower-extremity ulcers, is giving way to venous duplex ultrasound, which is not quite as accurate but spares patients the pain associated with the older procedure.
Roughly 70% of chronic lower-extremity ulcers are of venous origin, Dr. Lemon noted.
She encounters quite a few patients who are hospitalized for what is mistakenly diagnosed as bilateral cellulitis, when their true problem is chronic venous insufficiency. The patient’s response to two questions makes it easy to differentiate the two disorders. One is, “Do your legs hurt more or itch more?”
“If the legs itch more, the patient doesn’t have cellulitis,” Dr. Lemon explained. “Cellulitis doesn’t itch. Also, ask the patient, ‘When did your legs last look normal?’ They usually say it was years ago. That’s not bilateral cellulitis – an acute problem requiring hospitalization. It’s a chronic problem requiring extensive chronic wound care.”
If the lower leg wound site looks like cellulitis, with redness, swelling, and warmth to touch, but it itches rather than hurts, she noted, it’s probably stasis dermatitis, which is very common in patients with venous lower-extremity ulcers. The treatment is a potent topical steroid.
“Don’t be afraid of potent steroids,” Dr. Lemon said. “There is so much inflammation in those tissues, they need a potent steroid on the leg. I usually prescribe fluocinonide 0.05% because it’s reliably beneficial.”
An exudative venous wound should receive a moist dressing.
“Forget what your granny told you, and stop telling patients their wounds need to breathe,” she cautioned. “Wounds generally need to be suffocated and covered with an ointment like Vaseline. A dry wound heals about six times slower than a moist one; that’s been extensively studied in the dermatology, surgery, and burn literature.”
If, after 5-6 months of Dr. Lemon’s efforts, a patient’s wound still isn’t healing, the dermatologist will obtain a venous surgical consultation. In some reported series, surgical treatment of insufficiency – venous stripping – has resulted in improved healing time and fewer recurrent ulcers.
Dr. Lemon reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM THE ANNUAL INTERNAL MEDICINE PROGRAM
Bicarb, acetylcysteine during angiography don’t protect kidneys
Periprocedural administration of intravenous sodium bicarbonate did not improve outcomes compared with standard sodium chloride in patients with impaired kidney function undergoing angiography, according to results of a randomized study of 5,177 patients.
In addition, there was no benefit for oral acetylcysteine administration over placebo for mitigating those same postangiography risks, Steven D. Weisbord, MD, said at the American Heart Association scientific sessions in Anaheim, Calif.
Hypothetically, both sodium bicarbonate and acetylcysteine could help prevent acute kidney injury associated with contrast material used during angiography, said Dr. Weisbord of the University of Pittsburgh.
However, multiple studies of the two agents have yielded “inconsistent results … consequently, equipoise exists regarding these interventions, despite their widespread use in clinical practice,” Dr. Weisbord said.
To provide more definitive evidence, Dr. Weisbord and his colleagues conducted PRESERVE, a multicenter, randomized, controlled trial comprising 5,177 patients scheduled for angiography who were at high risk of renal complications. Using a 2-by-2 factorial design, patients were randomized to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride, and to 5 days of oral acetylcysteine or oral placebo.
They found no significant differences between arms in the study’s composite primary endpoint of death, need for dialysis, or persistent increase in serum creatinine by 50% or more.
That composite endpoint occurred in 4.4% of patients receiving sodium bicarbonate, and similarly in 4.7% of patients receiving sodium chloride.
Likewise, the endpoint occurred in 4.6% of patients in the acetylcysteine group and 4.5% of the placebo group, Dr. Weisbord reported.
The investigators had planned to enroll 7,680 patients, but the sponsor of the trial stopped the study after enrollment of 5,177 based on the results showing no significant benefit of either treatment, he noted.
There are a few reasons why results of PRESERVE might show a lack of benefit for these agents, in contrast to some previous studies suggesting both the treatments might reduce risk of contrast-associated renal complications in high-risk patients.
Notably, “most of these interventions have been underpowered,” Dr. Weisbord noted.
Also, most previous trials used a primary endpoint of increase in blood creatinine level within days of the angiography. By contrast, the primary endpoint of the current study was a composite of serious adverse events “that are recognized sequelae of acute kidney injury,” he added.
Although subsequent investigations could shed new light on the controversy, the findings of PRESERVE support the “strong likelihood that these interventions are not clinically effective” in preventing acute kidney injury or longer-term adverse outcomes after angiography, he concluded.
The PRESERVE results were published simultaneously with Dr. Weisbord’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1710933).
The study was supported by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia. Dr. Weisbord reported receiving personal fees from Durect outside the submitted work.
Periprocedural administration of intravenous sodium bicarbonate did not improve outcomes compared with standard sodium chloride in patients with impaired kidney function undergoing angiography, according to results of a randomized study of 5,177 patients.
In addition, there was no benefit for oral acetylcysteine administration over placebo for mitigating those same postangiography risks, Steven D. Weisbord, MD, said at the American Heart Association scientific sessions in Anaheim, Calif.
Hypothetically, both sodium bicarbonate and acetylcysteine could help prevent acute kidney injury associated with contrast material used during angiography, said Dr. Weisbord of the University of Pittsburgh.
However, multiple studies of the two agents have yielded “inconsistent results … consequently, equipoise exists regarding these interventions, despite their widespread use in clinical practice,” Dr. Weisbord said.
To provide more definitive evidence, Dr. Weisbord and his colleagues conducted PRESERVE, a multicenter, randomized, controlled trial comprising 5,177 patients scheduled for angiography who were at high risk of renal complications. Using a 2-by-2 factorial design, patients were randomized to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride, and to 5 days of oral acetylcysteine or oral placebo.
They found no significant differences between arms in the study’s composite primary endpoint of death, need for dialysis, or persistent increase in serum creatinine by 50% or more.
That composite endpoint occurred in 4.4% of patients receiving sodium bicarbonate, and similarly in 4.7% of patients receiving sodium chloride.
Likewise, the endpoint occurred in 4.6% of patients in the acetylcysteine group and 4.5% of the placebo group, Dr. Weisbord reported.
The investigators had planned to enroll 7,680 patients, but the sponsor of the trial stopped the study after enrollment of 5,177 based on the results showing no significant benefit of either treatment, he noted.
There are a few reasons why results of PRESERVE might show a lack of benefit for these agents, in contrast to some previous studies suggesting both the treatments might reduce risk of contrast-associated renal complications in high-risk patients.
Notably, “most of these interventions have been underpowered,” Dr. Weisbord noted.
Also, most previous trials used a primary endpoint of increase in blood creatinine level within days of the angiography. By contrast, the primary endpoint of the current study was a composite of serious adverse events “that are recognized sequelae of acute kidney injury,” he added.
Although subsequent investigations could shed new light on the controversy, the findings of PRESERVE support the “strong likelihood that these interventions are not clinically effective” in preventing acute kidney injury or longer-term adverse outcomes after angiography, he concluded.
The PRESERVE results were published simultaneously with Dr. Weisbord’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1710933).
The study was supported by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia. Dr. Weisbord reported receiving personal fees from Durect outside the submitted work.
Periprocedural administration of intravenous sodium bicarbonate did not improve outcomes compared with standard sodium chloride in patients with impaired kidney function undergoing angiography, according to results of a randomized study of 5,177 patients.
In addition, there was no benefit for oral acetylcysteine administration over placebo for mitigating those same postangiography risks, Steven D. Weisbord, MD, said at the American Heart Association scientific sessions in Anaheim, Calif.
Hypothetically, both sodium bicarbonate and acetylcysteine could help prevent acute kidney injury associated with contrast material used during angiography, said Dr. Weisbord of the University of Pittsburgh.
However, multiple studies of the two agents have yielded “inconsistent results … consequently, equipoise exists regarding these interventions, despite their widespread use in clinical practice,” Dr. Weisbord said.
To provide more definitive evidence, Dr. Weisbord and his colleagues conducted PRESERVE, a multicenter, randomized, controlled trial comprising 5,177 patients scheduled for angiography who were at high risk of renal complications. Using a 2-by-2 factorial design, patients were randomized to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride, and to 5 days of oral acetylcysteine or oral placebo.
They found no significant differences between arms in the study’s composite primary endpoint of death, need for dialysis, or persistent increase in serum creatinine by 50% or more.
That composite endpoint occurred in 4.4% of patients receiving sodium bicarbonate, and similarly in 4.7% of patients receiving sodium chloride.
Likewise, the endpoint occurred in 4.6% of patients in the acetylcysteine group and 4.5% of the placebo group, Dr. Weisbord reported.
The investigators had planned to enroll 7,680 patients, but the sponsor of the trial stopped the study after enrollment of 5,177 based on the results showing no significant benefit of either treatment, he noted.
There are a few reasons why results of PRESERVE might show a lack of benefit for these agents, in contrast to some previous studies suggesting both the treatments might reduce risk of contrast-associated renal complications in high-risk patients.
Notably, “most of these interventions have been underpowered,” Dr. Weisbord noted.
Also, most previous trials used a primary endpoint of increase in blood creatinine level within days of the angiography. By contrast, the primary endpoint of the current study was a composite of serious adverse events “that are recognized sequelae of acute kidney injury,” he added.
Although subsequent investigations could shed new light on the controversy, the findings of PRESERVE support the “strong likelihood that these interventions are not clinically effective” in preventing acute kidney injury or longer-term adverse outcomes after angiography, he concluded.
The PRESERVE results were published simultaneously with Dr. Weisbord’s presentation (N Engl J Med. 2017 Nov 12. doi: 10.1056/NEJMoa1710933).
The study was supported by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia. Dr. Weisbord reported receiving personal fees from Durect outside the submitted work.
FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: The composite primary endpoint of death, need for dialysis, or persistent increase in serum creatinine was similar regardless of which treatments the patients received.
Data source: PRESERVE, a randomized study using a 2-by-2 factorial design to evaluate intravenous sodium bicarbonate versus sodium chloride and acetylcysteine versus placebo in 5,177 patients at high risk of renal complications.
Disclosures: PRESERVE was supported by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia. Dr. Weisbord reported receiving personal fees from Durect outside the submitted work.
Understanding patient process flow
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
This phase of the QI project aims at a thorough understanding of the process flow of a patient, from being transferred from outside the hospital, receiving tertiary care services at Dartmouth-Hitchcock Medical Center, to being discharged to a rehabilitation facility/skilled nursing facility.
I am conducting interviews with key stakeholders to understand the current processes and needs for improvement. The key stakeholders include but are not limited to infectious disease, hospital medicine, nursing, case management, and psychiatry services.
I have developed an interview guide to facilitate the interviews. Based on a framework similar to SWOT analysis, the key questions include: (1) what makes this patient population particularly difficult to receive appropriate care/support? (2) What makes them difficult to be discharged when tertiary service is completed? (3) What can help them stay longer in the community and delay/prevent readmission?
I am working on retrieving clinical data from medical records and an infectious disease service database, and am going to analyze current patient status. Key metrics will include but not limited to length of stay, 30‐day readmission rate, patient satisfaction rating, infectious disease provider follow-up rate, and hospitalization cost.
A challenge I foresee I will encounter is deciding on a focused area for the improvement project. The constraints may be coming from clinical data availability or the willingness for the stakeholder to participate. For this purpose, I am going to ask each stakeholder about their priorities, and what they view as the most urgent or important aspects to improve. I also hope to identify stakeholders who might already have been thinking or working on improving care for this patient population.
I will address the data availability issue by following up closely with the infectious disease service. After I develop a general sense of the data, I will work with the interdisciplinary team to decide on a focused area for improvement.
One unexpected thing I learned during the last month was project planning. Initially, I was struggling with putting the details of the project together. I recalled later that at business school we often use timelines to facilitate project planning. I carved out two hours of my time. On a piece of paper, I wrote down one-by-one the tasks I need to accomplish for each phase of the study. I also set up an internal deadline for communications and deliverables with my advisor. Now I can track my progress much better and am confident that the project will move towards its landmarks.
Yun Li is an MD/MBA student attending Geisel School of Medicine and Tuck School of Business at Dartmouth. She obtained her Bachelor of Arts degree from Hanover College double-majoring in Economics and Biological Chemistry. Ms. Li participated in research in injury epidemiology and genetics, and has conducted studies on traditional Tibetan medicine, rural health, health NGOs, and digital health. Her career interest is practicing hospital medicine and geriatrics as a clinician/administrator, either in the US or China. Ms. Li is a student member of the Society of Hospital Medicine.
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
This phase of the QI project aims at a thorough understanding of the process flow of a patient, from being transferred from outside the hospital, receiving tertiary care services at Dartmouth-Hitchcock Medical Center, to being discharged to a rehabilitation facility/skilled nursing facility.
I am conducting interviews with key stakeholders to understand the current processes and needs for improvement. The key stakeholders include but are not limited to infectious disease, hospital medicine, nursing, case management, and psychiatry services.
I have developed an interview guide to facilitate the interviews. Based on a framework similar to SWOT analysis, the key questions include: (1) what makes this patient population particularly difficult to receive appropriate care/support? (2) What makes them difficult to be discharged when tertiary service is completed? (3) What can help them stay longer in the community and delay/prevent readmission?
I am working on retrieving clinical data from medical records and an infectious disease service database, and am going to analyze current patient status. Key metrics will include but not limited to length of stay, 30‐day readmission rate, patient satisfaction rating, infectious disease provider follow-up rate, and hospitalization cost.
A challenge I foresee I will encounter is deciding on a focused area for the improvement project. The constraints may be coming from clinical data availability or the willingness for the stakeholder to participate. For this purpose, I am going to ask each stakeholder about their priorities, and what they view as the most urgent or important aspects to improve. I also hope to identify stakeholders who might already have been thinking or working on improving care for this patient population.
I will address the data availability issue by following up closely with the infectious disease service. After I develop a general sense of the data, I will work with the interdisciplinary team to decide on a focused area for improvement.
One unexpected thing I learned during the last month was project planning. Initially, I was struggling with putting the details of the project together. I recalled later that at business school we often use timelines to facilitate project planning. I carved out two hours of my time. On a piece of paper, I wrote down one-by-one the tasks I need to accomplish for each phase of the study. I also set up an internal deadline for communications and deliverables with my advisor. Now I can track my progress much better and am confident that the project will move towards its landmarks.
Yun Li is an MD/MBA student attending Geisel School of Medicine and Tuck School of Business at Dartmouth. She obtained her Bachelor of Arts degree from Hanover College double-majoring in Economics and Biological Chemistry. Ms. Li participated in research in injury epidemiology and genetics, and has conducted studies on traditional Tibetan medicine, rural health, health NGOs, and digital health. Her career interest is practicing hospital medicine and geriatrics as a clinician/administrator, either in the US or China. Ms. Li is a student member of the Society of Hospital Medicine.
Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-18 year, offering two options for students to receive funding and engage in scholarly work during their first, second and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.
This phase of the QI project aims at a thorough understanding of the process flow of a patient, from being transferred from outside the hospital, receiving tertiary care services at Dartmouth-Hitchcock Medical Center, to being discharged to a rehabilitation facility/skilled nursing facility.
I am conducting interviews with key stakeholders to understand the current processes and needs for improvement. The key stakeholders include but are not limited to infectious disease, hospital medicine, nursing, case management, and psychiatry services.
I have developed an interview guide to facilitate the interviews. Based on a framework similar to SWOT analysis, the key questions include: (1) what makes this patient population particularly difficult to receive appropriate care/support? (2) What makes them difficult to be discharged when tertiary service is completed? (3) What can help them stay longer in the community and delay/prevent readmission?
I am working on retrieving clinical data from medical records and an infectious disease service database, and am going to analyze current patient status. Key metrics will include but not limited to length of stay, 30‐day readmission rate, patient satisfaction rating, infectious disease provider follow-up rate, and hospitalization cost.
A challenge I foresee I will encounter is deciding on a focused area for the improvement project. The constraints may be coming from clinical data availability or the willingness for the stakeholder to participate. For this purpose, I am going to ask each stakeholder about their priorities, and what they view as the most urgent or important aspects to improve. I also hope to identify stakeholders who might already have been thinking or working on improving care for this patient population.
I will address the data availability issue by following up closely with the infectious disease service. After I develop a general sense of the data, I will work with the interdisciplinary team to decide on a focused area for improvement.
One unexpected thing I learned during the last month was project planning. Initially, I was struggling with putting the details of the project together. I recalled later that at business school we often use timelines to facilitate project planning. I carved out two hours of my time. On a piece of paper, I wrote down one-by-one the tasks I need to accomplish for each phase of the study. I also set up an internal deadline for communications and deliverables with my advisor. Now I can track my progress much better and am confident that the project will move towards its landmarks.
Yun Li is an MD/MBA student attending Geisel School of Medicine and Tuck School of Business at Dartmouth. She obtained her Bachelor of Arts degree from Hanover College double-majoring in Economics and Biological Chemistry. Ms. Li participated in research in injury epidemiology and genetics, and has conducted studies on traditional Tibetan medicine, rural health, health NGOs, and digital health. Her career interest is practicing hospital medicine and geriatrics as a clinician/administrator, either in the US or China. Ms. Li is a student member of the Society of Hospital Medicine.
Prenatal maternal anxiety linked to hyperactivity in offspring as teenagers
PARIS – Maternal somatic anxiety during pregnancy and early childhood is associated in dose-response fashion with increased hyperactivity symptoms in mothers’ teenage children, according to an update from the landmark Avon Longitudinal Study of Parents and Offspring.
Perhaps the most intriguing finding in the new analysis was that the dose-response effect did not apply to the offspring of mothers in the highest quintile of somatic anxiety as measured during pregnancy and early childhood.
“It’s possible that a ceiling effect exists for those children that are exposed to continuous high levels of anxiety from pregnancy up to 5 years old,” Blanca Bolea-Alamanac, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
Dr. Bolea-Alamanac of the department of psychiatry at the University of Toronto offered a couple possible explanations for this apparent ceiling effect. One is that children continuously exposed to high levels of maternal stress hormones in utero and through breast feeding become desensitized to the effects of those hormones in ways that affect their future behavior.
Another possibility is that children exposed to very high levels of anxiety in early life later develop internalizing-type symptoms rather than externalizing hyperactivity-type symptoms, she continued.
The Avon Longitudinal Study of Parents and Children is a birth cohort study conducted in Southwest England, where women who were pregnant in 1990 and their 14,062 offspring have been followed prospectively for 26 years.
Dr. Bolea-Alamanac’s analysis included the 8,725 women with maternal anxiety assessments obtained at 18 and 32 weeks of pregnancy, as well as at 8 weeks, 8 months, 2.67 years, and 5 years post partum. Maternal anxiety was measured using the Crown-Crisp Experiential Index, which provided a specific indicator of somatic anxiety via responses to questions including, “Are you troubled by dizziness or shortness of breath?” “Do you experience a tingling or prickling sensation in your body, arms, or legs?” “Have you felt that you may faint, feel sick, or have indigestion?” and “Do you experience extra sweating?” The response options to each question were “never,” “sometimes,” “often,” or “very often.”
All women understandably experienced increased anxiety during pregnancy, peaking in the weeks shortly prior to delivery. But by examining the totality of data obtained at two time points in pregnancy and four points post pregnancy, the psychiatrist was able to construct a model with five distinct quintiles of maternal anxiety.
Hyperactivity symptoms were assessed in 3,417 of their offspring using the Strengths and Difficulties Questionnaire hyperactivity subscale.
Class 1, the reference class, was comprised of women with low anxiety during pregnancy and after delivery. In a logistic regression analysis adjusted for maternal age, alcohol intake, and education, life events during pregnancy, socioeconomic status, and the child’s sex, the women in class 2 were at 1.44-fold increased risk of having a hyperactive teenager. Those who were more anxious, in class 3, were at 1.87-fold increased risk, and those in class 4 were at 2.5-fold greater risk than those in class 1. All those increased risks were statistically significant.
In contrast, women in class 5 – those who scored highest for somatic anxiety both in pregnancy and during the next 5 years – had only a nonsignificant trend toward an increased risk of having a hyperactive teenager.
The association between prenatal and postnatal maternal somatic anxiety and hyperactivity symptoms in their children seen in the Avon study is consistent with Barker’s theory, according to Dr. Bolea-Alamanac. Barker’s theory, developed by the prominent late British epidemiologist David Barker, MD, PhD, holds that intrauterine influences interact with the environment at birth to produce specific disease risks for the child. Dr. Barker’s theory has gained considerable traction over the years, as evidenced by the creation of the multidisciplinary International Society for Developmental Origins of Health and Disease.
Dr. Bolea-Alamanac reported having no relevant financial conflicts of interest.
PARIS – Maternal somatic anxiety during pregnancy and early childhood is associated in dose-response fashion with increased hyperactivity symptoms in mothers’ teenage children, according to an update from the landmark Avon Longitudinal Study of Parents and Offspring.
Perhaps the most intriguing finding in the new analysis was that the dose-response effect did not apply to the offspring of mothers in the highest quintile of somatic anxiety as measured during pregnancy and early childhood.
“It’s possible that a ceiling effect exists for those children that are exposed to continuous high levels of anxiety from pregnancy up to 5 years old,” Blanca Bolea-Alamanac, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
Dr. Bolea-Alamanac of the department of psychiatry at the University of Toronto offered a couple possible explanations for this apparent ceiling effect. One is that children continuously exposed to high levels of maternal stress hormones in utero and through breast feeding become desensitized to the effects of those hormones in ways that affect their future behavior.
Another possibility is that children exposed to very high levels of anxiety in early life later develop internalizing-type symptoms rather than externalizing hyperactivity-type symptoms, she continued.
The Avon Longitudinal Study of Parents and Children is a birth cohort study conducted in Southwest England, where women who were pregnant in 1990 and their 14,062 offspring have been followed prospectively for 26 years.
Dr. Bolea-Alamanac’s analysis included the 8,725 women with maternal anxiety assessments obtained at 18 and 32 weeks of pregnancy, as well as at 8 weeks, 8 months, 2.67 years, and 5 years post partum. Maternal anxiety was measured using the Crown-Crisp Experiential Index, which provided a specific indicator of somatic anxiety via responses to questions including, “Are you troubled by dizziness or shortness of breath?” “Do you experience a tingling or prickling sensation in your body, arms, or legs?” “Have you felt that you may faint, feel sick, or have indigestion?” and “Do you experience extra sweating?” The response options to each question were “never,” “sometimes,” “often,” or “very often.”
All women understandably experienced increased anxiety during pregnancy, peaking in the weeks shortly prior to delivery. But by examining the totality of data obtained at two time points in pregnancy and four points post pregnancy, the psychiatrist was able to construct a model with five distinct quintiles of maternal anxiety.
Hyperactivity symptoms were assessed in 3,417 of their offspring using the Strengths and Difficulties Questionnaire hyperactivity subscale.
Class 1, the reference class, was comprised of women with low anxiety during pregnancy and after delivery. In a logistic regression analysis adjusted for maternal age, alcohol intake, and education, life events during pregnancy, socioeconomic status, and the child’s sex, the women in class 2 were at 1.44-fold increased risk of having a hyperactive teenager. Those who were more anxious, in class 3, were at 1.87-fold increased risk, and those in class 4 were at 2.5-fold greater risk than those in class 1. All those increased risks were statistically significant.
In contrast, women in class 5 – those who scored highest for somatic anxiety both in pregnancy and during the next 5 years – had only a nonsignificant trend toward an increased risk of having a hyperactive teenager.
The association between prenatal and postnatal maternal somatic anxiety and hyperactivity symptoms in their children seen in the Avon study is consistent with Barker’s theory, according to Dr. Bolea-Alamanac. Barker’s theory, developed by the prominent late British epidemiologist David Barker, MD, PhD, holds that intrauterine influences interact with the environment at birth to produce specific disease risks for the child. Dr. Barker’s theory has gained considerable traction over the years, as evidenced by the creation of the multidisciplinary International Society for Developmental Origins of Health and Disease.
Dr. Bolea-Alamanac reported having no relevant financial conflicts of interest.
PARIS – Maternal somatic anxiety during pregnancy and early childhood is associated in dose-response fashion with increased hyperactivity symptoms in mothers’ teenage children, according to an update from the landmark Avon Longitudinal Study of Parents and Offspring.
Perhaps the most intriguing finding in the new analysis was that the dose-response effect did not apply to the offspring of mothers in the highest quintile of somatic anxiety as measured during pregnancy and early childhood.
“It’s possible that a ceiling effect exists for those children that are exposed to continuous high levels of anxiety from pregnancy up to 5 years old,” Blanca Bolea-Alamanac, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
Dr. Bolea-Alamanac of the department of psychiatry at the University of Toronto offered a couple possible explanations for this apparent ceiling effect. One is that children continuously exposed to high levels of maternal stress hormones in utero and through breast feeding become desensitized to the effects of those hormones in ways that affect their future behavior.
Another possibility is that children exposed to very high levels of anxiety in early life later develop internalizing-type symptoms rather than externalizing hyperactivity-type symptoms, she continued.
The Avon Longitudinal Study of Parents and Children is a birth cohort study conducted in Southwest England, where women who were pregnant in 1990 and their 14,062 offspring have been followed prospectively for 26 years.
Dr. Bolea-Alamanac’s analysis included the 8,725 women with maternal anxiety assessments obtained at 18 and 32 weeks of pregnancy, as well as at 8 weeks, 8 months, 2.67 years, and 5 years post partum. Maternal anxiety was measured using the Crown-Crisp Experiential Index, which provided a specific indicator of somatic anxiety via responses to questions including, “Are you troubled by dizziness or shortness of breath?” “Do you experience a tingling or prickling sensation in your body, arms, or legs?” “Have you felt that you may faint, feel sick, or have indigestion?” and “Do you experience extra sweating?” The response options to each question were “never,” “sometimes,” “often,” or “very often.”
All women understandably experienced increased anxiety during pregnancy, peaking in the weeks shortly prior to delivery. But by examining the totality of data obtained at two time points in pregnancy and four points post pregnancy, the psychiatrist was able to construct a model with five distinct quintiles of maternal anxiety.
Hyperactivity symptoms were assessed in 3,417 of their offspring using the Strengths and Difficulties Questionnaire hyperactivity subscale.
Class 1, the reference class, was comprised of women with low anxiety during pregnancy and after delivery. In a logistic regression analysis adjusted for maternal age, alcohol intake, and education, life events during pregnancy, socioeconomic status, and the child’s sex, the women in class 2 were at 1.44-fold increased risk of having a hyperactive teenager. Those who were more anxious, in class 3, were at 1.87-fold increased risk, and those in class 4 were at 2.5-fold greater risk than those in class 1. All those increased risks were statistically significant.
In contrast, women in class 5 – those who scored highest for somatic anxiety both in pregnancy and during the next 5 years – had only a nonsignificant trend toward an increased risk of having a hyperactive teenager.
The association between prenatal and postnatal maternal somatic anxiety and hyperactivity symptoms in their children seen in the Avon study is consistent with Barker’s theory, according to Dr. Bolea-Alamanac. Barker’s theory, developed by the prominent late British epidemiologist David Barker, MD, PhD, holds that intrauterine influences interact with the environment at birth to produce specific disease risks for the child. Dr. Barker’s theory has gained considerable traction over the years, as evidenced by the creation of the multidisciplinary International Society for Developmental Origins of Health and Disease.
Dr. Bolea-Alamanac reported having no relevant financial conflicts of interest.
AT THE ECNP CONGRESS
Key clinical point:
Major finding: Women in the fourth quintile of somatic anxiety level during pregnancy and early childhood were at 2.5-fold increased risk of later having a hyperactive 16-year-old, compared with women in the lowest quintile of somatic anxiety.
Data source: Data gathered prospectively in the landmark Avon Longitudinal Study of Parents and Offspring.
Disclosures: The study presenter reported having no relevant financial conflicts of interest.
OCD linked to lower education attainment
Obsessive-compulsive disorder could be detrimental to educational attainment, particularly if diagnosed before the age of 18 years, according to a study published online Nov. 15.
A Swedish population-based birth cohort study identified 15,120 individuals who had been diagnosed with obsessive-compulsive disorder (OCD, 11,482 of whom were in families with full siblings discordant for OCD.
Individuals with OCD were also 57% less likely to complete upper secondary school, 28% less likely to start a university degree, 41% less likely to finish that degree, and 48% less likely to complete postgraduate education, compared to individuals without OCD.
“The association was global rather than being limited to a particular course; patients were more likely to fail each of the core and additional courses in compulsory school and less likely to achieve each level of education, from primary school to postgraduate education,” wrote Ana Pérez-Vigil, MD, of the Center for Psychiatry Research at Karolinska Institutet, Stockholm, and her coauthors.
The authors noted that as the education impairment seemed greatest at the end of upper secondary school but reduced during university, individuals with OCD might cope better with their symptoms as they age or receive evidence-based treatment.
“These individuals might be able to find alternative routes to access university, such as the locally funded school system for adults who have failed to complete primary or secondary school (known as komvux in Sweden),” they wrote. “Thus, early educational failure does not necessarily condemn individuals to lifelong educational ostracism.”
People with OCD also were 53% less likely to be eligible to access a vocational program (95% confidence interval, 0.45-0.50) and 49% less likely to be eligible for an academic program in upper secondary school (95% CI, 0.58-0.63), compared with the general population, after adjustment for factors such as sex, year of birth, and parental age at birth of the participant.
Early diagnosis – before the age of 18 years – was associated with even worse educational outcomes, compared with those diagnosed after the age of 18.
Excluding individuals with other comorbidities such as attention-deficit/hyperactivity disorder attenuated the results slightly, but individuals with OCD still showed significantly worse educational attainment than that of the general population.
Dr. Pérez-Vigil and her coauthors said detecting and treating OCD early might help patients “fulfill their educational potential.”
Several authors of the study were supported by grants from the International OCD Foundation; the Alicia Koplowitz Foundation; the Swedish Research Council for Health, Working Life, and Welfare; and the Karolinska Institute. Two authors declared royalties from a publishing company, and one declared speaking fees and a research grant from Shire Pharmaceuticals, all of which were outside the submitted work. No other conflicts of interest were declared.
Obsessive-compulsive disorder could be detrimental to educational attainment, particularly if diagnosed before the age of 18 years, according to a study published online Nov. 15.
A Swedish population-based birth cohort study identified 15,120 individuals who had been diagnosed with obsessive-compulsive disorder (OCD, 11,482 of whom were in families with full siblings discordant for OCD.
Individuals with OCD were also 57% less likely to complete upper secondary school, 28% less likely to start a university degree, 41% less likely to finish that degree, and 48% less likely to complete postgraduate education, compared to individuals without OCD.
“The association was global rather than being limited to a particular course; patients were more likely to fail each of the core and additional courses in compulsory school and less likely to achieve each level of education, from primary school to postgraduate education,” wrote Ana Pérez-Vigil, MD, of the Center for Psychiatry Research at Karolinska Institutet, Stockholm, and her coauthors.
The authors noted that as the education impairment seemed greatest at the end of upper secondary school but reduced during university, individuals with OCD might cope better with their symptoms as they age or receive evidence-based treatment.
“These individuals might be able to find alternative routes to access university, such as the locally funded school system for adults who have failed to complete primary or secondary school (known as komvux in Sweden),” they wrote. “Thus, early educational failure does not necessarily condemn individuals to lifelong educational ostracism.”
People with OCD also were 53% less likely to be eligible to access a vocational program (95% confidence interval, 0.45-0.50) and 49% less likely to be eligible for an academic program in upper secondary school (95% CI, 0.58-0.63), compared with the general population, after adjustment for factors such as sex, year of birth, and parental age at birth of the participant.
Early diagnosis – before the age of 18 years – was associated with even worse educational outcomes, compared with those diagnosed after the age of 18.
Excluding individuals with other comorbidities such as attention-deficit/hyperactivity disorder attenuated the results slightly, but individuals with OCD still showed significantly worse educational attainment than that of the general population.
Dr. Pérez-Vigil and her coauthors said detecting and treating OCD early might help patients “fulfill their educational potential.”
Several authors of the study were supported by grants from the International OCD Foundation; the Alicia Koplowitz Foundation; the Swedish Research Council for Health, Working Life, and Welfare; and the Karolinska Institute. Two authors declared royalties from a publishing company, and one declared speaking fees and a research grant from Shire Pharmaceuticals, all of which were outside the submitted work. No other conflicts of interest were declared.
Obsessive-compulsive disorder could be detrimental to educational attainment, particularly if diagnosed before the age of 18 years, according to a study published online Nov. 15.
A Swedish population-based birth cohort study identified 15,120 individuals who had been diagnosed with obsessive-compulsive disorder (OCD, 11,482 of whom were in families with full siblings discordant for OCD.
Individuals with OCD were also 57% less likely to complete upper secondary school, 28% less likely to start a university degree, 41% less likely to finish that degree, and 48% less likely to complete postgraduate education, compared to individuals without OCD.
“The association was global rather than being limited to a particular course; patients were more likely to fail each of the core and additional courses in compulsory school and less likely to achieve each level of education, from primary school to postgraduate education,” wrote Ana Pérez-Vigil, MD, of the Center for Psychiatry Research at Karolinska Institutet, Stockholm, and her coauthors.
The authors noted that as the education impairment seemed greatest at the end of upper secondary school but reduced during university, individuals with OCD might cope better with their symptoms as they age or receive evidence-based treatment.
“These individuals might be able to find alternative routes to access university, such as the locally funded school system for adults who have failed to complete primary or secondary school (known as komvux in Sweden),” they wrote. “Thus, early educational failure does not necessarily condemn individuals to lifelong educational ostracism.”
People with OCD also were 53% less likely to be eligible to access a vocational program (95% confidence interval, 0.45-0.50) and 49% less likely to be eligible for an academic program in upper secondary school (95% CI, 0.58-0.63), compared with the general population, after adjustment for factors such as sex, year of birth, and parental age at birth of the participant.
Early diagnosis – before the age of 18 years – was associated with even worse educational outcomes, compared with those diagnosed after the age of 18.
Excluding individuals with other comorbidities such as attention-deficit/hyperactivity disorder attenuated the results slightly, but individuals with OCD still showed significantly worse educational attainment than that of the general population.
Dr. Pérez-Vigil and her coauthors said detecting and treating OCD early might help patients “fulfill their educational potential.”
Several authors of the study were supported by grants from the International OCD Foundation; the Alicia Koplowitz Foundation; the Swedish Research Council for Health, Working Life, and Welfare; and the Karolinska Institute. Two authors declared royalties from a publishing company, and one declared speaking fees and a research grant from Shire Pharmaceuticals, all of which were outside the submitted work. No other conflicts of interest were declared.
FROM JAMA PSYCHIATRY
Key clinical point: Obsessive-compulsive disorder is associated with a decrease in education attainment, particularly if diagnosed before the age of 18 years.
Major finding: Individuals with obsessive-compulsive disorder are significantly less likely to complete upper secondary school and significantly less likely to pass courses in the last year of compulsory education.
Data source: A Swedish population-based birth cohort study of 15,120 individuals who had been diagnosed with obsessive-compulsive disorder.
Disclosures: Several authors of the study were supported by grants from the International OCD Foundation; the Alicia Koplowitz Foundation; the Swedish Research Council for Health, Working Life, and Welfare; and the Karolinska Institute. Two authors declared royalties from a publishing company, and one declared speaking fees and a research grant from Shire Pharmaceuticals, all of which were outside the submitted work. No other conflicts of interest were declared.
Debunking Actinic Keratosis Myths: Do All Actinic Keratoses Progress to Squamous Cell Carcinoma?
Myth: Hypertrophic actinic keratoses are more likely to progress to squamous cell carcinoma
Actinic keratosis (AK) indicates cumulative UV exposure and is the initial lesion in the majority of invasive cutaneous squamous cell carcinomas (SCCs). However, most AKs do not progress to invasive SCC and it currently is not possible to clinically or histopathologically determine which AK lesions will progress to SCC.
The rates of progression of individual AK lesions to SCC vary. In 2011, Feldman and Fleischer summarized 6 studies of 560 to 6691 patients with AK. The AK progression to SCC was found to range from 0.075% per year per lesion to 14% over 5 years.
Criscione et al found that the risk of progression of AK to primary SCC was 0.60% at 1 year and 2.57% at 4 years. In this study, 187 primary SCCs were diagnosed after enrollment, with 65% arising in previously clinically diagnosed and documented AKs. Therefore, although the authors noted low risks of progression of AK to SCC, they observed that the majority of SCCs arose from AKs.
The risk for progression of AK to invasive SCC with the potential for metastasis warrants treatment of AK with lesion- or field-directed therapy or a combined approach when indicated. Dermatologists also should monitor AK patients closely.
Expert Commentary
It’s a myth that hypertrophic lesions are more likely to turn into SCC. In fact, it’s the lesions with follicular extension that are more likely to progress to SCC. These may be hypertrophic or atrophic or simple AKs. The genetics of AKs that become hypertrophic may be different from those that become invasive. These lesions may be more likely to first grow outward before becoming invasive.
—Gary Goldenberg (New York, New York)
Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention trial. Cancer. 2009;115:2523-2530.
Feldman SR, Fleischer AB Jr. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87:201-207.
Pandey S, Mercer SE, Dallas K, et al. Evaluation of the prognostic significance of follicular extension in actinic keratoses. J Clin Aesthet Dermatol. 2012;5:25-28.
Myth: Hypertrophic actinic keratoses are more likely to progress to squamous cell carcinoma
Actinic keratosis (AK) indicates cumulative UV exposure and is the initial lesion in the majority of invasive cutaneous squamous cell carcinomas (SCCs). However, most AKs do not progress to invasive SCC and it currently is not possible to clinically or histopathologically determine which AK lesions will progress to SCC.
The rates of progression of individual AK lesions to SCC vary. In 2011, Feldman and Fleischer summarized 6 studies of 560 to 6691 patients with AK. The AK progression to SCC was found to range from 0.075% per year per lesion to 14% over 5 years.
Criscione et al found that the risk of progression of AK to primary SCC was 0.60% at 1 year and 2.57% at 4 years. In this study, 187 primary SCCs were diagnosed after enrollment, with 65% arising in previously clinically diagnosed and documented AKs. Therefore, although the authors noted low risks of progression of AK to SCC, they observed that the majority of SCCs arose from AKs.
The risk for progression of AK to invasive SCC with the potential for metastasis warrants treatment of AK with lesion- or field-directed therapy or a combined approach when indicated. Dermatologists also should monitor AK patients closely.
Expert Commentary
It’s a myth that hypertrophic lesions are more likely to turn into SCC. In fact, it’s the lesions with follicular extension that are more likely to progress to SCC. These may be hypertrophic or atrophic or simple AKs. The genetics of AKs that become hypertrophic may be different from those that become invasive. These lesions may be more likely to first grow outward before becoming invasive.
—Gary Goldenberg (New York, New York)
Myth: Hypertrophic actinic keratoses are more likely to progress to squamous cell carcinoma
Actinic keratosis (AK) indicates cumulative UV exposure and is the initial lesion in the majority of invasive cutaneous squamous cell carcinomas (SCCs). However, most AKs do not progress to invasive SCC and it currently is not possible to clinically or histopathologically determine which AK lesions will progress to SCC.
The rates of progression of individual AK lesions to SCC vary. In 2011, Feldman and Fleischer summarized 6 studies of 560 to 6691 patients with AK. The AK progression to SCC was found to range from 0.075% per year per lesion to 14% over 5 years.
Criscione et al found that the risk of progression of AK to primary SCC was 0.60% at 1 year and 2.57% at 4 years. In this study, 187 primary SCCs were diagnosed after enrollment, with 65% arising in previously clinically diagnosed and documented AKs. Therefore, although the authors noted low risks of progression of AK to SCC, they observed that the majority of SCCs arose from AKs.
The risk for progression of AK to invasive SCC with the potential for metastasis warrants treatment of AK with lesion- or field-directed therapy or a combined approach when indicated. Dermatologists also should monitor AK patients closely.
Expert Commentary
It’s a myth that hypertrophic lesions are more likely to turn into SCC. In fact, it’s the lesions with follicular extension that are more likely to progress to SCC. These may be hypertrophic or atrophic or simple AKs. The genetics of AKs that become hypertrophic may be different from those that become invasive. These lesions may be more likely to first grow outward before becoming invasive.
—Gary Goldenberg (New York, New York)
Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention trial. Cancer. 2009;115:2523-2530.
Feldman SR, Fleischer AB Jr. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87:201-207.
Pandey S, Mercer SE, Dallas K, et al. Evaluation of the prognostic significance of follicular extension in actinic keratoses. J Clin Aesthet Dermatol. 2012;5:25-28.
Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention trial. Cancer. 2009;115:2523-2530.
Feldman SR, Fleischer AB Jr. Progression of actinic keratosis to squamous cell carcinoma revisited: clinical and treatment implications. Cutis. 2011;87:201-207.
Pandey S, Mercer SE, Dallas K, et al. Evaluation of the prognostic significance of follicular extension in actinic keratoses. J Clin Aesthet Dermatol. 2012;5:25-28.
