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Immunomodulators for pediatric skin diseases
WASHINGTON – At the annual meeting of the American Academy of Dermatology, colleagues A. Yasmine Kirkorian, MD, a pediatric dermatologist at George Washington University, Washington, and interim chief of pediatric dermatology at Children’s National Health System, and Adam Friedman, MD, professor and interim chair of dermatology at the university, sat down with Dermatology News and discussed their presentations at a session on the use of immunomodulators for inflammatory and neoplastic skin diseases.
In this video, , with her clinical pearls and practical considerations for treating atopic dermatitis, psoriasis, and hidradenitis suppurativa in pediatric patients, covering both on- and off-label treatments.
“Children sometimes require systemic treatment and we shouldn’t hold it back from them because of their age; if they’re severely ill ... they need to be treated,” she said, summing up one of her main points.
During the interview immediately after the AAD meeting, she mentioned dupilumab, which was approved by the Food and Drug Administration for treatment of moderate to severe AD in patients aged 12-17 years.
Dr. Friedman and Dr. Kirkorian reported having no financial disclosures.
WASHINGTON – At the annual meeting of the American Academy of Dermatology, colleagues A. Yasmine Kirkorian, MD, a pediatric dermatologist at George Washington University, Washington, and interim chief of pediatric dermatology at Children’s National Health System, and Adam Friedman, MD, professor and interim chair of dermatology at the university, sat down with Dermatology News and discussed their presentations at a session on the use of immunomodulators for inflammatory and neoplastic skin diseases.
In this video, , with her clinical pearls and practical considerations for treating atopic dermatitis, psoriasis, and hidradenitis suppurativa in pediatric patients, covering both on- and off-label treatments.
“Children sometimes require systemic treatment and we shouldn’t hold it back from them because of their age; if they’re severely ill ... they need to be treated,” she said, summing up one of her main points.
During the interview immediately after the AAD meeting, she mentioned dupilumab, which was approved by the Food and Drug Administration for treatment of moderate to severe AD in patients aged 12-17 years.
Dr. Friedman and Dr. Kirkorian reported having no financial disclosures.
WASHINGTON – At the annual meeting of the American Academy of Dermatology, colleagues A. Yasmine Kirkorian, MD, a pediatric dermatologist at George Washington University, Washington, and interim chief of pediatric dermatology at Children’s National Health System, and Adam Friedman, MD, professor and interim chair of dermatology at the university, sat down with Dermatology News and discussed their presentations at a session on the use of immunomodulators for inflammatory and neoplastic skin diseases.
In this video, , with her clinical pearls and practical considerations for treating atopic dermatitis, psoriasis, and hidradenitis suppurativa in pediatric patients, covering both on- and off-label treatments.
“Children sometimes require systemic treatment and we shouldn’t hold it back from them because of their age; if they’re severely ill ... they need to be treated,” she said, summing up one of her main points.
During the interview immediately after the AAD meeting, she mentioned dupilumab, which was approved by the Food and Drug Administration for treatment of moderate to severe AD in patients aged 12-17 years.
Dr. Friedman and Dr. Kirkorian reported having no financial disclosures.
ACC to offer new certification for transcatheter valve repair, replacement
The American College of Cardiology announced at its ACC Quality Summit in New Orleans that it will offer a Transcatheter Valve Certification to assist hospitals that perform transcatheter valve repair and replacement.
The certification is an external review process that will allow hospitals to meet standards for multidisciplinary teams, formalized training, shared decision making, and registry performance. During the certification process, hospitals will learn best practices for implementing evidence-based medicine in the care of individual patients and identify quality improvement opportunities.
The Transcatheter Valve Certification will be launched in mid-2019. To earn the certification, hospitals must already participate in an established national clinical database.
“. This certification incorporates recent guidelines and expert consensus statements regarding the care of patients requiring transcatheter valve therapies,” Phillip D. Levy, MD, chair of the ACC accreditation management board, said in a press release.
Find the full press release on the ACC website.
The American College of Cardiology announced at its ACC Quality Summit in New Orleans that it will offer a Transcatheter Valve Certification to assist hospitals that perform transcatheter valve repair and replacement.
The certification is an external review process that will allow hospitals to meet standards for multidisciplinary teams, formalized training, shared decision making, and registry performance. During the certification process, hospitals will learn best practices for implementing evidence-based medicine in the care of individual patients and identify quality improvement opportunities.
The Transcatheter Valve Certification will be launched in mid-2019. To earn the certification, hospitals must already participate in an established national clinical database.
“. This certification incorporates recent guidelines and expert consensus statements regarding the care of patients requiring transcatheter valve therapies,” Phillip D. Levy, MD, chair of the ACC accreditation management board, said in a press release.
Find the full press release on the ACC website.
The American College of Cardiology announced at its ACC Quality Summit in New Orleans that it will offer a Transcatheter Valve Certification to assist hospitals that perform transcatheter valve repair and replacement.
The certification is an external review process that will allow hospitals to meet standards for multidisciplinary teams, formalized training, shared decision making, and registry performance. During the certification process, hospitals will learn best practices for implementing evidence-based medicine in the care of individual patients and identify quality improvement opportunities.
The Transcatheter Valve Certification will be launched in mid-2019. To earn the certification, hospitals must already participate in an established national clinical database.
“. This certification incorporates recent guidelines and expert consensus statements regarding the care of patients requiring transcatheter valve therapies,” Phillip D. Levy, MD, chair of the ACC accreditation management board, said in a press release.
Find the full press release on the ACC website.
‘Difficult’ discussions reduced anxiety, depression in life-limiting cancer patients
A program to encourage difficult discussions between seriously ill patients and their oncologists reduced anxiety and depression in a recent randomized trial, but its impact on patient-centered outcomes were uncertain.
Goal-concordant care and peacefulness at the end of life, the coprimary study outcomes, were not significantly different between patients who received the quality improvement intervention and controls in the study, which included 91 clinicians providing care for 278 patients with advanced cancer.
However, it’s not clear whether the intervention, known as the Serious Illness Care Program (SICP), failed to improve those outcomes, or if there simply weren’t enough patients in the trial to detect a meaningful difference, according to investigators led by Rachelle Bernacki, MD, of Brigham and Women’s Hospital and the Harvard School of Public Health, Boston.
“Our challenges reflect the need in our field for patient-centered measures of communication that are agreed upon, validated, and demonstrably sensitive to communication interventions,” wrote Dr. Bernacki and her coinvestigators in a report on the study published in JAMA Internal Medicine.
However, the SICP intervention did clearly result in a larger number of serious-illness conversations that occurred earlier and were of higher quality, the investigators wrote in a separate report published in JAMA Oncology. In medical records reviewed after the patients’ deaths, 96% of those who received the intervention had a documented serious-illness conversation with their oncology clinician, compared with 79% of controls (P = .005), according to that report.
The conversations among SICP recipients occurred a median of 2.4 months earlier than controls, and had a greater focus on values and goals, prognosis and understanding of illness, and treatment preferences.
These outcomes are reassuring, since patients “want, require, and deserve” conversations about serious illness, regardless of their impact on measurable outcomes, the authors of an editorial published in JAMA Oncology wrote.
The SICP intervention included a communication guide for clinicians, who also participated in a 2.5-hour training session designed to improve their serious-illness conversation skills. Other aspects of the program for clinicians included email reminders before outpatient visits, a specialized EMR template, and personal coaching. The program also included patient tools, including a letter introducing the intervention and a guide for continuing the conversation with their family.
The study did not demonstrate a significant difference in peacefulness, as measured by the validated Peace, Equanimity, and Acceptance in the Cancer Experience questionnaire, or in goal-concordant care, which was measured by asking patients to select goals of importance, and then asking caregivers to rate whether those goals had been met at the end of life.
However, patients in the SICP group reported less anxiety and depression 14 weeks into the trial, according to the investigators. The proportion of patients reporting moderate to severe anxiety at that time point was 10.2% for the intervention group versus 5.0% for controls (P = .05), while the proportion reporting depression symptoms was 20.8% for the intervention versus 10.6% for controls (P = .04).
The anxiety reduction was maintained at 24 weeks, though the depression reduction was not, the investigators wrote, adding that there were no differences in survival between arms.
Taken together, these results suggest that oncology clinicians can discuss difficult topics without causing harm, and with potential benefit, the investigators wrote in a discussion of their results.
“Further development of serious illness communication interventions will require more reliable and well-accepted patient-centered outcome measures and additional testing of the effect on patients throughout their illness trajectory,” they concluded.
Dr. Bernacki reported no disclosures. Coauthor Susan D. Block, MD, reported compensation from Up to Date and Atul A. Gawande, MD, MPH, reported receiving compensation from health care writing and media and is employed by a health care venture formed by Amazon, Berkshire Hathaway, and JPMorgan Chase.
SOURCE: Bernacki R et al. JAMA Intern Med. 2018 Mar 14. doi: 10.1001/jamainternmed.2019.0077.
While results of this rigorous and innovative clinical trial are disappointing because of an apparent lack of impact on the primary outcomes of care, oncologists still must initiate serious illness conversations with advanced cancer patients at risk of dying in the foreseeable future, according to the authors of an editorial.
Doing so is important “not because this will necessarily improve outcomes, but because patients want, require, and deserve to know what is coming,” wrote Belinda E. Kiely, MBBS, PhD, FRACP, and Martin R. Stockler, MBBS, MSc, FRACP.
Those difficult conversations should not stop at discussing the limits of care, but should include a discussion of the patient’s preferences, priorities, and values, Dr. Kiely and Dr. Stockler wrote, adding that they should be documented in the EMR to ensure they are accessible to other health care providers.
“If nothing else, oncologists should be reassured that having these conversations is unlikely to increase anxiety or depression in their patients,” wrote the editorial authors, referencing the significantly reduced incidence of those secondary endpoints in the study.
However, conversations alone may not be enough to improve other patient-centered outcomes, based on the inability of this trial to demonstrate significant improvements in goal-centered care or peacefulness at the end of life.
Moreover, building this Serious Illness Care Program intervention into a health system could be complicated and may require significant resources.
“Simple, pragmatic, and effective tactics are needed to ensure greater generalizability and widespread applicability of such programs,” the authors concluded.
Dr. Kiely and Dr. Stockler are with the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney. Their editorial appears in JAMA Oncology. Dr. Stockler reported grants outside the submitted work from Astellas, Amgen, AstraZeneca, Cancer Australia, Celgene, Bionomics, Bayer, Medivation, Merck, National Health and Medical Research Council Australia, Pfizer, Roche, Sanofi, and Tilray.
While results of this rigorous and innovative clinical trial are disappointing because of an apparent lack of impact on the primary outcomes of care, oncologists still must initiate serious illness conversations with advanced cancer patients at risk of dying in the foreseeable future, according to the authors of an editorial.
Doing so is important “not because this will necessarily improve outcomes, but because patients want, require, and deserve to know what is coming,” wrote Belinda E. Kiely, MBBS, PhD, FRACP, and Martin R. Stockler, MBBS, MSc, FRACP.
Those difficult conversations should not stop at discussing the limits of care, but should include a discussion of the patient’s preferences, priorities, and values, Dr. Kiely and Dr. Stockler wrote, adding that they should be documented in the EMR to ensure they are accessible to other health care providers.
“If nothing else, oncologists should be reassured that having these conversations is unlikely to increase anxiety or depression in their patients,” wrote the editorial authors, referencing the significantly reduced incidence of those secondary endpoints in the study.
However, conversations alone may not be enough to improve other patient-centered outcomes, based on the inability of this trial to demonstrate significant improvements in goal-centered care or peacefulness at the end of life.
Moreover, building this Serious Illness Care Program intervention into a health system could be complicated and may require significant resources.
“Simple, pragmatic, and effective tactics are needed to ensure greater generalizability and widespread applicability of such programs,” the authors concluded.
Dr. Kiely and Dr. Stockler are with the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney. Their editorial appears in JAMA Oncology. Dr. Stockler reported grants outside the submitted work from Astellas, Amgen, AstraZeneca, Cancer Australia, Celgene, Bionomics, Bayer, Medivation, Merck, National Health and Medical Research Council Australia, Pfizer, Roche, Sanofi, and Tilray.
While results of this rigorous and innovative clinical trial are disappointing because of an apparent lack of impact on the primary outcomes of care, oncologists still must initiate serious illness conversations with advanced cancer patients at risk of dying in the foreseeable future, according to the authors of an editorial.
Doing so is important “not because this will necessarily improve outcomes, but because patients want, require, and deserve to know what is coming,” wrote Belinda E. Kiely, MBBS, PhD, FRACP, and Martin R. Stockler, MBBS, MSc, FRACP.
Those difficult conversations should not stop at discussing the limits of care, but should include a discussion of the patient’s preferences, priorities, and values, Dr. Kiely and Dr. Stockler wrote, adding that they should be documented in the EMR to ensure they are accessible to other health care providers.
“If nothing else, oncologists should be reassured that having these conversations is unlikely to increase anxiety or depression in their patients,” wrote the editorial authors, referencing the significantly reduced incidence of those secondary endpoints in the study.
However, conversations alone may not be enough to improve other patient-centered outcomes, based on the inability of this trial to demonstrate significant improvements in goal-centered care or peacefulness at the end of life.
Moreover, building this Serious Illness Care Program intervention into a health system could be complicated and may require significant resources.
“Simple, pragmatic, and effective tactics are needed to ensure greater generalizability and widespread applicability of such programs,” the authors concluded.
Dr. Kiely and Dr. Stockler are with the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney. Their editorial appears in JAMA Oncology. Dr. Stockler reported grants outside the submitted work from Astellas, Amgen, AstraZeneca, Cancer Australia, Celgene, Bionomics, Bayer, Medivation, Merck, National Health and Medical Research Council Australia, Pfizer, Roche, Sanofi, and Tilray.
A program to encourage difficult discussions between seriously ill patients and their oncologists reduced anxiety and depression in a recent randomized trial, but its impact on patient-centered outcomes were uncertain.
Goal-concordant care and peacefulness at the end of life, the coprimary study outcomes, were not significantly different between patients who received the quality improvement intervention and controls in the study, which included 91 clinicians providing care for 278 patients with advanced cancer.
However, it’s not clear whether the intervention, known as the Serious Illness Care Program (SICP), failed to improve those outcomes, or if there simply weren’t enough patients in the trial to detect a meaningful difference, according to investigators led by Rachelle Bernacki, MD, of Brigham and Women’s Hospital and the Harvard School of Public Health, Boston.
“Our challenges reflect the need in our field for patient-centered measures of communication that are agreed upon, validated, and demonstrably sensitive to communication interventions,” wrote Dr. Bernacki and her coinvestigators in a report on the study published in JAMA Internal Medicine.
However, the SICP intervention did clearly result in a larger number of serious-illness conversations that occurred earlier and were of higher quality, the investigators wrote in a separate report published in JAMA Oncology. In medical records reviewed after the patients’ deaths, 96% of those who received the intervention had a documented serious-illness conversation with their oncology clinician, compared with 79% of controls (P = .005), according to that report.
The conversations among SICP recipients occurred a median of 2.4 months earlier than controls, and had a greater focus on values and goals, prognosis and understanding of illness, and treatment preferences.
These outcomes are reassuring, since patients “want, require, and deserve” conversations about serious illness, regardless of their impact on measurable outcomes, the authors of an editorial published in JAMA Oncology wrote.
The SICP intervention included a communication guide for clinicians, who also participated in a 2.5-hour training session designed to improve their serious-illness conversation skills. Other aspects of the program for clinicians included email reminders before outpatient visits, a specialized EMR template, and personal coaching. The program also included patient tools, including a letter introducing the intervention and a guide for continuing the conversation with their family.
The study did not demonstrate a significant difference in peacefulness, as measured by the validated Peace, Equanimity, and Acceptance in the Cancer Experience questionnaire, or in goal-concordant care, which was measured by asking patients to select goals of importance, and then asking caregivers to rate whether those goals had been met at the end of life.
However, patients in the SICP group reported less anxiety and depression 14 weeks into the trial, according to the investigators. The proportion of patients reporting moderate to severe anxiety at that time point was 10.2% for the intervention group versus 5.0% for controls (P = .05), while the proportion reporting depression symptoms was 20.8% for the intervention versus 10.6% for controls (P = .04).
The anxiety reduction was maintained at 24 weeks, though the depression reduction was not, the investigators wrote, adding that there were no differences in survival between arms.
Taken together, these results suggest that oncology clinicians can discuss difficult topics without causing harm, and with potential benefit, the investigators wrote in a discussion of their results.
“Further development of serious illness communication interventions will require more reliable and well-accepted patient-centered outcome measures and additional testing of the effect on patients throughout their illness trajectory,” they concluded.
Dr. Bernacki reported no disclosures. Coauthor Susan D. Block, MD, reported compensation from Up to Date and Atul A. Gawande, MD, MPH, reported receiving compensation from health care writing and media and is employed by a health care venture formed by Amazon, Berkshire Hathaway, and JPMorgan Chase.
SOURCE: Bernacki R et al. JAMA Intern Med. 2018 Mar 14. doi: 10.1001/jamainternmed.2019.0077.
A program to encourage difficult discussions between seriously ill patients and their oncologists reduced anxiety and depression in a recent randomized trial, but its impact on patient-centered outcomes were uncertain.
Goal-concordant care and peacefulness at the end of life, the coprimary study outcomes, were not significantly different between patients who received the quality improvement intervention and controls in the study, which included 91 clinicians providing care for 278 patients with advanced cancer.
However, it’s not clear whether the intervention, known as the Serious Illness Care Program (SICP), failed to improve those outcomes, or if there simply weren’t enough patients in the trial to detect a meaningful difference, according to investigators led by Rachelle Bernacki, MD, of Brigham and Women’s Hospital and the Harvard School of Public Health, Boston.
“Our challenges reflect the need in our field for patient-centered measures of communication that are agreed upon, validated, and demonstrably sensitive to communication interventions,” wrote Dr. Bernacki and her coinvestigators in a report on the study published in JAMA Internal Medicine.
However, the SICP intervention did clearly result in a larger number of serious-illness conversations that occurred earlier and were of higher quality, the investigators wrote in a separate report published in JAMA Oncology. In medical records reviewed after the patients’ deaths, 96% of those who received the intervention had a documented serious-illness conversation with their oncology clinician, compared with 79% of controls (P = .005), according to that report.
The conversations among SICP recipients occurred a median of 2.4 months earlier than controls, and had a greater focus on values and goals, prognosis and understanding of illness, and treatment preferences.
These outcomes are reassuring, since patients “want, require, and deserve” conversations about serious illness, regardless of their impact on measurable outcomes, the authors of an editorial published in JAMA Oncology wrote.
The SICP intervention included a communication guide for clinicians, who also participated in a 2.5-hour training session designed to improve their serious-illness conversation skills. Other aspects of the program for clinicians included email reminders before outpatient visits, a specialized EMR template, and personal coaching. The program also included patient tools, including a letter introducing the intervention and a guide for continuing the conversation with their family.
The study did not demonstrate a significant difference in peacefulness, as measured by the validated Peace, Equanimity, and Acceptance in the Cancer Experience questionnaire, or in goal-concordant care, which was measured by asking patients to select goals of importance, and then asking caregivers to rate whether those goals had been met at the end of life.
However, patients in the SICP group reported less anxiety and depression 14 weeks into the trial, according to the investigators. The proportion of patients reporting moderate to severe anxiety at that time point was 10.2% for the intervention group versus 5.0% for controls (P = .05), while the proportion reporting depression symptoms was 20.8% for the intervention versus 10.6% for controls (P = .04).
The anxiety reduction was maintained at 24 weeks, though the depression reduction was not, the investigators wrote, adding that there were no differences in survival between arms.
Taken together, these results suggest that oncology clinicians can discuss difficult topics without causing harm, and with potential benefit, the investigators wrote in a discussion of their results.
“Further development of serious illness communication interventions will require more reliable and well-accepted patient-centered outcome measures and additional testing of the effect on patients throughout their illness trajectory,” they concluded.
Dr. Bernacki reported no disclosures. Coauthor Susan D. Block, MD, reported compensation from Up to Date and Atul A. Gawande, MD, MPH, reported receiving compensation from health care writing and media and is employed by a health care venture formed by Amazon, Berkshire Hathaway, and JPMorgan Chase.
SOURCE: Bernacki R et al. JAMA Intern Med. 2018 Mar 14. doi: 10.1001/jamainternmed.2019.0077.
FROM JAMA INTERNAL MEDICINE
Genomic sequencing sheds light on development of pediatric cancer
Genome sequencing technologies are providing a valuable new window into the development and progression of pediatric cancers, according to the authors of a review.
In contrast to adult cancers, which are frequently driven by oncogenic mutations, many pediatric cancers have a low burden of somatic mutations, wrote E. Alejandro Sweet-Cordero, MD, from the University of California, San Francisco, and Jaclyn A. Biegel, MD, from the University of Southern California in Science. Instead, large-scale sequencing studies have found that childhood cancers have a much higher likelihood of being caused by germline mutations in genes that predispose development of cancer.
“Particularly surprising was the observation that even high-risk, highly aggressive cancers in many cases had no identifiable driver gene or pathway,” the authors wrote.
Some pediatric cancers do have identified driver genes, but even these are often different to those seen in adult cancers. The authors gave the example of one study of 1,699 patients and six types of cancer: This study identified 142 likely oncogenes, but only 45% of these matched those seen in the adult cancers.
Many pediatric cancers also have unique genetic features, such as the age-dependent gene fusion events, in which two genes join to form an oncogenic hybrid, and focal areas of gene deletion, which are often seen in pediatric acute myeloid leukemia but less so in adult forms of this cancer.
“In some instances, the fusion events involve genes that are known to be cancer drivers; this raises the intriguing possibility that some pediatric cancers are driven by ‘private’ oncogenic fusions,” the authors wrote, pointing out that this has daunting implications for the development of precision medicine. However they also noted that the presence of common gene fusion events could hold significance for choice of therapies; for example, central nervous system gliomas with the common BRAF V600E mutation may respond to specific BRAF inhibitors.
The authors drew particular attention to the role that genomic analysis could play in studying cancer during treatment and relapse, but they said few studies have explored this in pediatric patients.
“Such studies are critical given what we have learned from adult cancers, which show a capacity to evolve rapidly and acquire new driver mutations,” they wrote. One study found that only one-third of tumors with a potentially targetable genetic mutation had retained that target when analyzed at a later time.
On the issue of targeted therapy, the authors noted that no prospective study has yet looked at the use of sequencing approaches to define new therapies for pediatric cancer. However, they did refer to the Pediatric MATCH clinical trial, which is currently evaluating targeted therapies for relapsed solid tumors in children.
They also identified a need for research on predictors of treatment response in pediatric cancer.
“As the genetic variants that are associated with drug response are, by nature and design, variants present in the normal population, they are typically not included in DNA sequencing panels and are filtered out in WES [whole-exome sequencing] or WGS [whole-genome sequencing] bioinformatics pipelines,” they wrote.
They addressed the question of when to do germline testing in pediatric cancer, saying that, for most pediatric cancer patients, germline testing was indicated by the presence of a pathogenic genetic alternative affecting a gene known to be associated with a predisposition for germline cancer.
The authors suggested that data sharing was important to advancing genomic analysis in pediatric cancers because most of the studies so far had been relatively small. However, they highlighted emerging resources for large-scale analysis of pediatric cancer data, such as public portals for investigating discovery genomic data sets and data repositories of clinical-grade sequencing data.
The review was funded by the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sweet-Cordero A et al. Science 2019;363:1170-5.
Genome sequencing technologies are providing a valuable new window into the development and progression of pediatric cancers, according to the authors of a review.
In contrast to adult cancers, which are frequently driven by oncogenic mutations, many pediatric cancers have a low burden of somatic mutations, wrote E. Alejandro Sweet-Cordero, MD, from the University of California, San Francisco, and Jaclyn A. Biegel, MD, from the University of Southern California in Science. Instead, large-scale sequencing studies have found that childhood cancers have a much higher likelihood of being caused by germline mutations in genes that predispose development of cancer.
“Particularly surprising was the observation that even high-risk, highly aggressive cancers in many cases had no identifiable driver gene or pathway,” the authors wrote.
Some pediatric cancers do have identified driver genes, but even these are often different to those seen in adult cancers. The authors gave the example of one study of 1,699 patients and six types of cancer: This study identified 142 likely oncogenes, but only 45% of these matched those seen in the adult cancers.
Many pediatric cancers also have unique genetic features, such as the age-dependent gene fusion events, in which two genes join to form an oncogenic hybrid, and focal areas of gene deletion, which are often seen in pediatric acute myeloid leukemia but less so in adult forms of this cancer.
“In some instances, the fusion events involve genes that are known to be cancer drivers; this raises the intriguing possibility that some pediatric cancers are driven by ‘private’ oncogenic fusions,” the authors wrote, pointing out that this has daunting implications for the development of precision medicine. However they also noted that the presence of common gene fusion events could hold significance for choice of therapies; for example, central nervous system gliomas with the common BRAF V600E mutation may respond to specific BRAF inhibitors.
The authors drew particular attention to the role that genomic analysis could play in studying cancer during treatment and relapse, but they said few studies have explored this in pediatric patients.
“Such studies are critical given what we have learned from adult cancers, which show a capacity to evolve rapidly and acquire new driver mutations,” they wrote. One study found that only one-third of tumors with a potentially targetable genetic mutation had retained that target when analyzed at a later time.
On the issue of targeted therapy, the authors noted that no prospective study has yet looked at the use of sequencing approaches to define new therapies for pediatric cancer. However, they did refer to the Pediatric MATCH clinical trial, which is currently evaluating targeted therapies for relapsed solid tumors in children.
They also identified a need for research on predictors of treatment response in pediatric cancer.
“As the genetic variants that are associated with drug response are, by nature and design, variants present in the normal population, they are typically not included in DNA sequencing panels and are filtered out in WES [whole-exome sequencing] or WGS [whole-genome sequencing] bioinformatics pipelines,” they wrote.
They addressed the question of when to do germline testing in pediatric cancer, saying that, for most pediatric cancer patients, germline testing was indicated by the presence of a pathogenic genetic alternative affecting a gene known to be associated with a predisposition for germline cancer.
The authors suggested that data sharing was important to advancing genomic analysis in pediatric cancers because most of the studies so far had been relatively small. However, they highlighted emerging resources for large-scale analysis of pediatric cancer data, such as public portals for investigating discovery genomic data sets and data repositories of clinical-grade sequencing data.
The review was funded by the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sweet-Cordero A et al. Science 2019;363:1170-5.
Genome sequencing technologies are providing a valuable new window into the development and progression of pediatric cancers, according to the authors of a review.
In contrast to adult cancers, which are frequently driven by oncogenic mutations, many pediatric cancers have a low burden of somatic mutations, wrote E. Alejandro Sweet-Cordero, MD, from the University of California, San Francisco, and Jaclyn A. Biegel, MD, from the University of Southern California in Science. Instead, large-scale sequencing studies have found that childhood cancers have a much higher likelihood of being caused by germline mutations in genes that predispose development of cancer.
“Particularly surprising was the observation that even high-risk, highly aggressive cancers in many cases had no identifiable driver gene or pathway,” the authors wrote.
Some pediatric cancers do have identified driver genes, but even these are often different to those seen in adult cancers. The authors gave the example of one study of 1,699 patients and six types of cancer: This study identified 142 likely oncogenes, but only 45% of these matched those seen in the adult cancers.
Many pediatric cancers also have unique genetic features, such as the age-dependent gene fusion events, in which two genes join to form an oncogenic hybrid, and focal areas of gene deletion, which are often seen in pediatric acute myeloid leukemia but less so in adult forms of this cancer.
“In some instances, the fusion events involve genes that are known to be cancer drivers; this raises the intriguing possibility that some pediatric cancers are driven by ‘private’ oncogenic fusions,” the authors wrote, pointing out that this has daunting implications for the development of precision medicine. However they also noted that the presence of common gene fusion events could hold significance for choice of therapies; for example, central nervous system gliomas with the common BRAF V600E mutation may respond to specific BRAF inhibitors.
The authors drew particular attention to the role that genomic analysis could play in studying cancer during treatment and relapse, but they said few studies have explored this in pediatric patients.
“Such studies are critical given what we have learned from adult cancers, which show a capacity to evolve rapidly and acquire new driver mutations,” they wrote. One study found that only one-third of tumors with a potentially targetable genetic mutation had retained that target when analyzed at a later time.
On the issue of targeted therapy, the authors noted that no prospective study has yet looked at the use of sequencing approaches to define new therapies for pediatric cancer. However, they did refer to the Pediatric MATCH clinical trial, which is currently evaluating targeted therapies for relapsed solid tumors in children.
They also identified a need for research on predictors of treatment response in pediatric cancer.
“As the genetic variants that are associated with drug response are, by nature and design, variants present in the normal population, they are typically not included in DNA sequencing panels and are filtered out in WES [whole-exome sequencing] or WGS [whole-genome sequencing] bioinformatics pipelines,” they wrote.
They addressed the question of when to do germline testing in pediatric cancer, saying that, for most pediatric cancer patients, germline testing was indicated by the presence of a pathogenic genetic alternative affecting a gene known to be associated with a predisposition for germline cancer.
The authors suggested that data sharing was important to advancing genomic analysis in pediatric cancers because most of the studies so far had been relatively small. However, they highlighted emerging resources for large-scale analysis of pediatric cancer data, such as public portals for investigating discovery genomic data sets and data repositories of clinical-grade sequencing data.
The review was funded by the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Sweet-Cordero A et al. Science 2019;363:1170-5.
FROM SCIENCE
Key clinical point: Genome sequencing is providing valuable information on pediatric cancer development and progression.
Major finding: Many pediatric cancers have very different oncogenic drivers to adult cancers.
Study details: Review.
Disclosures: The review was funded by the National Cancer Institute. No conflicts of interest were declared.
Source: Sweet-Cordero EA et al. Science. 2019;363:1170-5.
MRD status at transplant predicts outcomes in ALL patients
HOUSTON – Acute lymphoblastic leukemia patients with measurable residual disease (MRD) negativity prior to hematopoietic cell transplantation achieve better outcomes than do those who are MRD positive, particularly when total body irradiation (TBI)–based conditioning is used, a large retrospective study suggests.
Of 2,780 ALL patients who underwent hematopoietic cell transplantation (HCT) in first or second complete remission (CR), and who were included in the study, 1,816 were MRD negative before transplantation and 964 were MRD positive.
Overall, with follow-up of 40-44 months, MRD positivity was a significant independent predictor of lower overall survival (OS; hazard ratio, 1.19), leukemia-free survival (LFS; HR, 1.26), and higher relapse incidence (RI; 1.51), Arnon Nagler, MD, reported at the Transplantation & Cellular Therapy Meetings.
Conditioning was TBI-based in 76% of the patients; when these patients were compared with those who received chemotherapy-based conditioning, they were found to have better OS, LFS, and RI (HRs, 0.75, 0.70, and 0.60, respectively), said Dr. Nagler, director of both the division of hematology and the bone marrow transplantation and cord blood bank at the Chaim Sheba Medical Center, Tel-Hashomer, and professor of medicine at Tel Aviv University, both in Israel.
“There was no significant interaction between the MRD status and the conditioning,” he said.
On multivariate analysis, MRD positivity was found to be associated with lower OS and LFS (HRs, 1.26 and 1.3), and higher RI (HR, 1.53) in the TBI group, and with higher RI (HR 1.58) in the chemotherapy group, he said. There was no significant association between MRD and other outcomes in this last cohort, he added, noting that TBI-based conditioning was associated with improved OS, LFS, and RI in both MRD-negative and MRD-positive patients.
“MRD is an extremely important prognostic factor for ALL,” he said, noting that its prognostic value in this setting has been established in multiple studies, and that MRD measured at the end of induction is increasingly used to guide further therapy.
However, although MRD detectable immediately before HCT is known to be associated with poor outcomes, it has been unclear if – or to what extent – this differs with different types of conditioning, he added.
“So the aim of this study was to explore if MRD detectable before allogeneic HCT for ALL is associated with different outcomes in adult patients receiving myeloablative conditioning, either TBI or chemotherapy based,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Patients included in the analysis had a median age of 38 years and underwent HCT between 2000 and 2017 using sibling or unrelated 9/10 or 10/10 matched donors. None received blinatumomab or inotuzumab, Dr. Nagler said, adding that more patients are likely to achieve MRD negativity with these agents.
It will be interesting to see if the prognostic value of MRD will remain as strong with the new agents, and if TBI will be “a strong factor in overall survival and disease-free survival” with modern immunotherapy, he concluded.
The study was conducted on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).
Dr. Nagler reported having no relevant financial disclosures.
SOURCE: Nagler A et al. TCT 2019, Abstract 7.
HOUSTON – Acute lymphoblastic leukemia patients with measurable residual disease (MRD) negativity prior to hematopoietic cell transplantation achieve better outcomes than do those who are MRD positive, particularly when total body irradiation (TBI)–based conditioning is used, a large retrospective study suggests.
Of 2,780 ALL patients who underwent hematopoietic cell transplantation (HCT) in first or second complete remission (CR), and who were included in the study, 1,816 were MRD negative before transplantation and 964 were MRD positive.
Overall, with follow-up of 40-44 months, MRD positivity was a significant independent predictor of lower overall survival (OS; hazard ratio, 1.19), leukemia-free survival (LFS; HR, 1.26), and higher relapse incidence (RI; 1.51), Arnon Nagler, MD, reported at the Transplantation & Cellular Therapy Meetings.
Conditioning was TBI-based in 76% of the patients; when these patients were compared with those who received chemotherapy-based conditioning, they were found to have better OS, LFS, and RI (HRs, 0.75, 0.70, and 0.60, respectively), said Dr. Nagler, director of both the division of hematology and the bone marrow transplantation and cord blood bank at the Chaim Sheba Medical Center, Tel-Hashomer, and professor of medicine at Tel Aviv University, both in Israel.
“There was no significant interaction between the MRD status and the conditioning,” he said.
On multivariate analysis, MRD positivity was found to be associated with lower OS and LFS (HRs, 1.26 and 1.3), and higher RI (HR, 1.53) in the TBI group, and with higher RI (HR 1.58) in the chemotherapy group, he said. There was no significant association between MRD and other outcomes in this last cohort, he added, noting that TBI-based conditioning was associated with improved OS, LFS, and RI in both MRD-negative and MRD-positive patients.
“MRD is an extremely important prognostic factor for ALL,” he said, noting that its prognostic value in this setting has been established in multiple studies, and that MRD measured at the end of induction is increasingly used to guide further therapy.
However, although MRD detectable immediately before HCT is known to be associated with poor outcomes, it has been unclear if – or to what extent – this differs with different types of conditioning, he added.
“So the aim of this study was to explore if MRD detectable before allogeneic HCT for ALL is associated with different outcomes in adult patients receiving myeloablative conditioning, either TBI or chemotherapy based,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Patients included in the analysis had a median age of 38 years and underwent HCT between 2000 and 2017 using sibling or unrelated 9/10 or 10/10 matched donors. None received blinatumomab or inotuzumab, Dr. Nagler said, adding that more patients are likely to achieve MRD negativity with these agents.
It will be interesting to see if the prognostic value of MRD will remain as strong with the new agents, and if TBI will be “a strong factor in overall survival and disease-free survival” with modern immunotherapy, he concluded.
The study was conducted on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).
Dr. Nagler reported having no relevant financial disclosures.
SOURCE: Nagler A et al. TCT 2019, Abstract 7.
HOUSTON – Acute lymphoblastic leukemia patients with measurable residual disease (MRD) negativity prior to hematopoietic cell transplantation achieve better outcomes than do those who are MRD positive, particularly when total body irradiation (TBI)–based conditioning is used, a large retrospective study suggests.
Of 2,780 ALL patients who underwent hematopoietic cell transplantation (HCT) in first or second complete remission (CR), and who were included in the study, 1,816 were MRD negative before transplantation and 964 were MRD positive.
Overall, with follow-up of 40-44 months, MRD positivity was a significant independent predictor of lower overall survival (OS; hazard ratio, 1.19), leukemia-free survival (LFS; HR, 1.26), and higher relapse incidence (RI; 1.51), Arnon Nagler, MD, reported at the Transplantation & Cellular Therapy Meetings.
Conditioning was TBI-based in 76% of the patients; when these patients were compared with those who received chemotherapy-based conditioning, they were found to have better OS, LFS, and RI (HRs, 0.75, 0.70, and 0.60, respectively), said Dr. Nagler, director of both the division of hematology and the bone marrow transplantation and cord blood bank at the Chaim Sheba Medical Center, Tel-Hashomer, and professor of medicine at Tel Aviv University, both in Israel.
“There was no significant interaction between the MRD status and the conditioning,” he said.
On multivariate analysis, MRD positivity was found to be associated with lower OS and LFS (HRs, 1.26 and 1.3), and higher RI (HR, 1.53) in the TBI group, and with higher RI (HR 1.58) in the chemotherapy group, he said. There was no significant association between MRD and other outcomes in this last cohort, he added, noting that TBI-based conditioning was associated with improved OS, LFS, and RI in both MRD-negative and MRD-positive patients.
“MRD is an extremely important prognostic factor for ALL,” he said, noting that its prognostic value in this setting has been established in multiple studies, and that MRD measured at the end of induction is increasingly used to guide further therapy.
However, although MRD detectable immediately before HCT is known to be associated with poor outcomes, it has been unclear if – or to what extent – this differs with different types of conditioning, he added.
“So the aim of this study was to explore if MRD detectable before allogeneic HCT for ALL is associated with different outcomes in adult patients receiving myeloablative conditioning, either TBI or chemotherapy based,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
Patients included in the analysis had a median age of 38 years and underwent HCT between 2000 and 2017 using sibling or unrelated 9/10 or 10/10 matched donors. None received blinatumomab or inotuzumab, Dr. Nagler said, adding that more patients are likely to achieve MRD negativity with these agents.
It will be interesting to see if the prognostic value of MRD will remain as strong with the new agents, and if TBI will be “a strong factor in overall survival and disease-free survival” with modern immunotherapy, he concluded.
The study was conducted on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).
Dr. Nagler reported having no relevant financial disclosures.
SOURCE: Nagler A et al. TCT 2019, Abstract 7.
REPORTING FROM TCT 2019
Ovarian cancer survivors carry burden of severe long-term fatigue
Women who have survived epithelial ovarian cancer (EOC) more often report severe long-term fatigue than healthy women, according to a case-control study involving more than 600 individuals.
Ovarian cancer survivors had a higher rate of sleep disturbance, neuropathy, and depression, reported lead author Florence Joly, MD, of Centre François Baclesse in Caen, France, and her colleagues. These factors likely contribute to severe long-term fatigue; a condition that has been minimally researched in EOC survivors.
“Long-term fatigue has been described as one of the most common and distressing adverse effects of cancer and its treatment,” the investigators wrote in Annals of Oncology. However, “Little is known about the prevalence of long-term fatigue in EOC survivors several years after treatment in comparison with age-matched healthy women.”
The study involved 318 EOC survivors who had not relapsed for at least 3 years, and 318 age-matched, healthy women. Survivors were 63 years old, on average, and split almost evenly between cases of early and advanced disease (50% stage I/II vs. 48% stage III/IV). Almost all patients had received platinum/taxane chemotherapy (99%). Average follow-up was 6 years.
Participants self-reported through questionnaires about physical activity (International Physical Activity Questionnaire), sleep disturbance ( Insomnia Severity Index), anxiety/depression (Hospital Anxiety and Depression Scale), neuropathy (Functional Assessment of Cancer Therapy-Taxane Neurotoxicity [FACT-Ntx]), quality of life ( Functional Assessment of Cancer Therapy-General/Ovarian), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Severe long-term fatigue was defined as a FACIT-F score of less than 37. Analysis was performed to find rates of severe long-term fatigue and contributing factors.
Although sociodemographic measures and global quality of life were similar between groups, 26% of EOC survivors reported severe long-term fatigue, compared with 13% of healthy women (P = .0004). Multivariable analysis revealed that three main factors contributed to this trend; worse neuropathy scores (FACT-Ntx 35 vs. 39), higher rates of depression (22% vs. 13%), and lower sleep quality (63% vs. 47%).
“These results highlight the need for continuous screening of sleep disturbance and depression as soon as the diagnosis of EOC is made, and for sleep disturbance interventions in EOC survivors,” the investigators wrote. “As pharmacological treatment seems to have limited efficacy, behavioral interventions should be offered to improve sleep quality and/or depressive symptoms.”
“Fewer than 20% of our EOC survivors and controls exercised regularly, a finding consistent with a recent study conducted in long-term EOC survivors,” the investigators noted. “Personalized clinical exercise programs were effective in improving fatigue and depression in a heterogeneous population of cancer survivors, so they should be promoted in EOC survivors [too].”
The study was funded by Fondation de France. The investigators disclosed financial relationships with AstraZeneca, Janssen, Sanofi, Novartis, and others.
SOURCE: Joly F et al. Ann Onc. 2019 Mar 9. doi: 10.1093/annonc/mdz074.
Women who have survived epithelial ovarian cancer (EOC) more often report severe long-term fatigue than healthy women, according to a case-control study involving more than 600 individuals.
Ovarian cancer survivors had a higher rate of sleep disturbance, neuropathy, and depression, reported lead author Florence Joly, MD, of Centre François Baclesse in Caen, France, and her colleagues. These factors likely contribute to severe long-term fatigue; a condition that has been minimally researched in EOC survivors.
“Long-term fatigue has been described as one of the most common and distressing adverse effects of cancer and its treatment,” the investigators wrote in Annals of Oncology. However, “Little is known about the prevalence of long-term fatigue in EOC survivors several years after treatment in comparison with age-matched healthy women.”
The study involved 318 EOC survivors who had not relapsed for at least 3 years, and 318 age-matched, healthy women. Survivors were 63 years old, on average, and split almost evenly between cases of early and advanced disease (50% stage I/II vs. 48% stage III/IV). Almost all patients had received platinum/taxane chemotherapy (99%). Average follow-up was 6 years.
Participants self-reported through questionnaires about physical activity (International Physical Activity Questionnaire), sleep disturbance ( Insomnia Severity Index), anxiety/depression (Hospital Anxiety and Depression Scale), neuropathy (Functional Assessment of Cancer Therapy-Taxane Neurotoxicity [FACT-Ntx]), quality of life ( Functional Assessment of Cancer Therapy-General/Ovarian), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Severe long-term fatigue was defined as a FACIT-F score of less than 37. Analysis was performed to find rates of severe long-term fatigue and contributing factors.
Although sociodemographic measures and global quality of life were similar between groups, 26% of EOC survivors reported severe long-term fatigue, compared with 13% of healthy women (P = .0004). Multivariable analysis revealed that three main factors contributed to this trend; worse neuropathy scores (FACT-Ntx 35 vs. 39), higher rates of depression (22% vs. 13%), and lower sleep quality (63% vs. 47%).
“These results highlight the need for continuous screening of sleep disturbance and depression as soon as the diagnosis of EOC is made, and for sleep disturbance interventions in EOC survivors,” the investigators wrote. “As pharmacological treatment seems to have limited efficacy, behavioral interventions should be offered to improve sleep quality and/or depressive symptoms.”
“Fewer than 20% of our EOC survivors and controls exercised regularly, a finding consistent with a recent study conducted in long-term EOC survivors,” the investigators noted. “Personalized clinical exercise programs were effective in improving fatigue and depression in a heterogeneous population of cancer survivors, so they should be promoted in EOC survivors [too].”
The study was funded by Fondation de France. The investigators disclosed financial relationships with AstraZeneca, Janssen, Sanofi, Novartis, and others.
SOURCE: Joly F et al. Ann Onc. 2019 Mar 9. doi: 10.1093/annonc/mdz074.
Women who have survived epithelial ovarian cancer (EOC) more often report severe long-term fatigue than healthy women, according to a case-control study involving more than 600 individuals.
Ovarian cancer survivors had a higher rate of sleep disturbance, neuropathy, and depression, reported lead author Florence Joly, MD, of Centre François Baclesse in Caen, France, and her colleagues. These factors likely contribute to severe long-term fatigue; a condition that has been minimally researched in EOC survivors.
“Long-term fatigue has been described as one of the most common and distressing adverse effects of cancer and its treatment,” the investigators wrote in Annals of Oncology. However, “Little is known about the prevalence of long-term fatigue in EOC survivors several years after treatment in comparison with age-matched healthy women.”
The study involved 318 EOC survivors who had not relapsed for at least 3 years, and 318 age-matched, healthy women. Survivors were 63 years old, on average, and split almost evenly between cases of early and advanced disease (50% stage I/II vs. 48% stage III/IV). Almost all patients had received platinum/taxane chemotherapy (99%). Average follow-up was 6 years.
Participants self-reported through questionnaires about physical activity (International Physical Activity Questionnaire), sleep disturbance ( Insomnia Severity Index), anxiety/depression (Hospital Anxiety and Depression Scale), neuropathy (Functional Assessment of Cancer Therapy-Taxane Neurotoxicity [FACT-Ntx]), quality of life ( Functional Assessment of Cancer Therapy-General/Ovarian), and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Severe long-term fatigue was defined as a FACIT-F score of less than 37. Analysis was performed to find rates of severe long-term fatigue and contributing factors.
Although sociodemographic measures and global quality of life were similar between groups, 26% of EOC survivors reported severe long-term fatigue, compared with 13% of healthy women (P = .0004). Multivariable analysis revealed that three main factors contributed to this trend; worse neuropathy scores (FACT-Ntx 35 vs. 39), higher rates of depression (22% vs. 13%), and lower sleep quality (63% vs. 47%).
“These results highlight the need for continuous screening of sleep disturbance and depression as soon as the diagnosis of EOC is made, and for sleep disturbance interventions in EOC survivors,” the investigators wrote. “As pharmacological treatment seems to have limited efficacy, behavioral interventions should be offered to improve sleep quality and/or depressive symptoms.”
“Fewer than 20% of our EOC survivors and controls exercised regularly, a finding consistent with a recent study conducted in long-term EOC survivors,” the investigators noted. “Personalized clinical exercise programs were effective in improving fatigue and depression in a heterogeneous population of cancer survivors, so they should be promoted in EOC survivors [too].”
The study was funded by Fondation de France. The investigators disclosed financial relationships with AstraZeneca, Janssen, Sanofi, Novartis, and others.
SOURCE: Joly F et al. Ann Onc. 2019 Mar 9. doi: 10.1093/annonc/mdz074.
FROM ANNALS OF ONCOLOGY
Secondary AML in first remission predicts outcomes
HOUSTON – Secondary acute myeloid leukemia (sAML) predicts outcomes after stem cell transplantation in first complete remission, whereas factors such as age, cytogenetics, and performance status are more relevant predictors of outcomes in patients with de novo AML, according to a large, registry-based analysis.
Of 11,439 patients with de novo AML and 1,325 with sAML identified in the registry, 7,691 and 909, respectively, underwent a stem cell transplant (SCT) in first complete remission (CR1), Bipin Savani, MD, said at the Transplantation & Cellular Therapies Meetings.
The 3-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) rates in those who underwent SCT in CR1 were higher in the sAML versus de novo AML groups (35% vs. 28.5% for CIR and 23.4% vs. 16.4% for NRM, respectively), said Dr. Savani, professor of medicine, director of the Long-Term Transplant Clinic, and medical director of the Stem Cell Transplant Processing Laboratory at Vanderbilt University Medical Center & Veterans Affairs Medical Center, Nashville, Tenn.
The 3-year overall survival (OS), leukemia-free survival (LFS), and graft-versus-host disease/relapse-free survival (GRFS) were significantly lower in the sAML group versus the de novo AML group (46.7% vs. 60.8% for OS; 41.6% vs. 55.1% for LFS; and 28.4% vs. 28.6% for GRFS).
Multivariate analysis controlling for risk factors and stratified by disease stage at SCT showed that sAML in CR1 was significantly associated with higher NRM (hazard ratio, 1.32) and CIR (HR, 1.28), and with lower LFS (HR, 1.30), OS (HR, 1.32) and GRFS (HR, 1.20).
Other significant predictors of OS in the model were age, cytogenetics, patient/donor sex combination, Karnofsky performance status (KPS), and donor, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
In the patients who underwent SCT for primary refractory AML (607 with de novo AML and 199 with sAML) or relapsed AML (1,009 with de novo AML and 124 with sAML), the outcomes were generally inferior to those seen with SCT in CR1. However, sAML in those patients did not predict outcomes, Dr. Savani said, noting that outcome in those cases were predicted by age, cytogenetics, and KPS.
In an analysis of 877 pairs matched for age, disease stage at SCT, KPS, conditioning, in vivo/ex vivo T-cell depletion, donor, donor/recipient sex and cytomegalovirus-status combination, cytogenetics, and graft source, the finding that sAML was associated with significantly higher NRM, and lower LFS, OS, and GRFS overall was confirmed.
However, stratification by stage at the time of SCT again showed that the differences between groups were only seen among those transplanted in CR1, and not in those with advanced disease at the time of transplant.
Patients included in the study were adults aged 18 years and older who underwent SCT for de novo or sAML from a matched related, unrelated, or T-cell replete haploidentical donor between 2000 and 2016.
The findings confirm the general belief that the prognosis in AML secondary to another hematologic neoplasia or malignant disease is poorer than that for de novo AML, and clarify the role of this difference for SCT, Dr. Savani said.
“These data may help to improve risk stratification and prognostic estimates after allogeneic hematopoietic cell transplantation for acute myeloid leukemia,” he concluded.
Dr. Savani reported having no financial disclosures.
SOURCE: Savani B et al. TCT 2019, Abstract 12.
HOUSTON – Secondary acute myeloid leukemia (sAML) predicts outcomes after stem cell transplantation in first complete remission, whereas factors such as age, cytogenetics, and performance status are more relevant predictors of outcomes in patients with de novo AML, according to a large, registry-based analysis.
Of 11,439 patients with de novo AML and 1,325 with sAML identified in the registry, 7,691 and 909, respectively, underwent a stem cell transplant (SCT) in first complete remission (CR1), Bipin Savani, MD, said at the Transplantation & Cellular Therapies Meetings.
The 3-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) rates in those who underwent SCT in CR1 were higher in the sAML versus de novo AML groups (35% vs. 28.5% for CIR and 23.4% vs. 16.4% for NRM, respectively), said Dr. Savani, professor of medicine, director of the Long-Term Transplant Clinic, and medical director of the Stem Cell Transplant Processing Laboratory at Vanderbilt University Medical Center & Veterans Affairs Medical Center, Nashville, Tenn.
The 3-year overall survival (OS), leukemia-free survival (LFS), and graft-versus-host disease/relapse-free survival (GRFS) were significantly lower in the sAML group versus the de novo AML group (46.7% vs. 60.8% for OS; 41.6% vs. 55.1% for LFS; and 28.4% vs. 28.6% for GRFS).
Multivariate analysis controlling for risk factors and stratified by disease stage at SCT showed that sAML in CR1 was significantly associated with higher NRM (hazard ratio, 1.32) and CIR (HR, 1.28), and with lower LFS (HR, 1.30), OS (HR, 1.32) and GRFS (HR, 1.20).
Other significant predictors of OS in the model were age, cytogenetics, patient/donor sex combination, Karnofsky performance status (KPS), and donor, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
In the patients who underwent SCT for primary refractory AML (607 with de novo AML and 199 with sAML) or relapsed AML (1,009 with de novo AML and 124 with sAML), the outcomes were generally inferior to those seen with SCT in CR1. However, sAML in those patients did not predict outcomes, Dr. Savani said, noting that outcome in those cases were predicted by age, cytogenetics, and KPS.
In an analysis of 877 pairs matched for age, disease stage at SCT, KPS, conditioning, in vivo/ex vivo T-cell depletion, donor, donor/recipient sex and cytomegalovirus-status combination, cytogenetics, and graft source, the finding that sAML was associated with significantly higher NRM, and lower LFS, OS, and GRFS overall was confirmed.
However, stratification by stage at the time of SCT again showed that the differences between groups were only seen among those transplanted in CR1, and not in those with advanced disease at the time of transplant.
Patients included in the study were adults aged 18 years and older who underwent SCT for de novo or sAML from a matched related, unrelated, or T-cell replete haploidentical donor between 2000 and 2016.
The findings confirm the general belief that the prognosis in AML secondary to another hematologic neoplasia or malignant disease is poorer than that for de novo AML, and clarify the role of this difference for SCT, Dr. Savani said.
“These data may help to improve risk stratification and prognostic estimates after allogeneic hematopoietic cell transplantation for acute myeloid leukemia,” he concluded.
Dr. Savani reported having no financial disclosures.
SOURCE: Savani B et al. TCT 2019, Abstract 12.
HOUSTON – Secondary acute myeloid leukemia (sAML) predicts outcomes after stem cell transplantation in first complete remission, whereas factors such as age, cytogenetics, and performance status are more relevant predictors of outcomes in patients with de novo AML, according to a large, registry-based analysis.
Of 11,439 patients with de novo AML and 1,325 with sAML identified in the registry, 7,691 and 909, respectively, underwent a stem cell transplant (SCT) in first complete remission (CR1), Bipin Savani, MD, said at the Transplantation & Cellular Therapies Meetings.
The 3-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) rates in those who underwent SCT in CR1 were higher in the sAML versus de novo AML groups (35% vs. 28.5% for CIR and 23.4% vs. 16.4% for NRM, respectively), said Dr. Savani, professor of medicine, director of the Long-Term Transplant Clinic, and medical director of the Stem Cell Transplant Processing Laboratory at Vanderbilt University Medical Center & Veterans Affairs Medical Center, Nashville, Tenn.
The 3-year overall survival (OS), leukemia-free survival (LFS), and graft-versus-host disease/relapse-free survival (GRFS) were significantly lower in the sAML group versus the de novo AML group (46.7% vs. 60.8% for OS; 41.6% vs. 55.1% for LFS; and 28.4% vs. 28.6% for GRFS).
Multivariate analysis controlling for risk factors and stratified by disease stage at SCT showed that sAML in CR1 was significantly associated with higher NRM (hazard ratio, 1.32) and CIR (HR, 1.28), and with lower LFS (HR, 1.30), OS (HR, 1.32) and GRFS (HR, 1.20).
Other significant predictors of OS in the model were age, cytogenetics, patient/donor sex combination, Karnofsky performance status (KPS), and donor, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
In the patients who underwent SCT for primary refractory AML (607 with de novo AML and 199 with sAML) or relapsed AML (1,009 with de novo AML and 124 with sAML), the outcomes were generally inferior to those seen with SCT in CR1. However, sAML in those patients did not predict outcomes, Dr. Savani said, noting that outcome in those cases were predicted by age, cytogenetics, and KPS.
In an analysis of 877 pairs matched for age, disease stage at SCT, KPS, conditioning, in vivo/ex vivo T-cell depletion, donor, donor/recipient sex and cytomegalovirus-status combination, cytogenetics, and graft source, the finding that sAML was associated with significantly higher NRM, and lower LFS, OS, and GRFS overall was confirmed.
However, stratification by stage at the time of SCT again showed that the differences between groups were only seen among those transplanted in CR1, and not in those with advanced disease at the time of transplant.
Patients included in the study were adults aged 18 years and older who underwent SCT for de novo or sAML from a matched related, unrelated, or T-cell replete haploidentical donor between 2000 and 2016.
The findings confirm the general belief that the prognosis in AML secondary to another hematologic neoplasia or malignant disease is poorer than that for de novo AML, and clarify the role of this difference for SCT, Dr. Savani said.
“These data may help to improve risk stratification and prognostic estimates after allogeneic hematopoietic cell transplantation for acute myeloid leukemia,” he concluded.
Dr. Savani reported having no financial disclosures.
SOURCE: Savani B et al. TCT 2019, Abstract 12.
REPORTING FROM TCT 2019
New cantharidin formulation alleviates molluscum contagiosum in pivotal trials
WASHINGTON – compared with placebo, according to the results of two trials presented at the annual meeting of the American Academy of Dermatology.
VP-102, a drug-device combination, was well tolerated and was not associated with serious adverse events.
No Food and Drug Administration–approved treatment is available for treating molluscum contagiosum, which is routinely treated with cantharidin, a naturally occurring vesicant.
VP-102 is a novel formulation of 0.7% cantharidin solution, provided in a single-use applicator, to provide consistent delivery and long-term drug stability.
To test the efficacy and safety of VP-102, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and his associates conducted the CAMP-1 (Cantharidin Application in Molluscum Patients) and CAMP-2 phase 3 studies, which had similar designs. The studies enrolled patients with molluscum contagiosum aged 2 years and older who had not received any treatment in the 2 weeks before enrollment. Patients were randomized to VP-102 or vehicle for 12 weeks. Treatment was administered topically to each lesion every 3 weeks for a maximum of four applications, and washed off with soap and warm water 24 hours after application.
The trials’ primary endpoint was the percentage of patients with complete clearance of their lesions. Secondary endpoints were the percentage of patients with complete clearance at 3, 6, and 9 weeks, and decrease in lesions over time. The researchers also assessed safety and tolerability.
In the two studies, 528 patients aged 2-60 years (mean age, approximately 7 years) were randomized to treatment or vehicle. About 30% of participants had prior treatment. The baseline lesion count ranged from 1 to 184.
At day 84, the proportion of patients in the VP-102 arm who achieved complete clearance of lesions was 46% in CAMP-1 and 54% in CAMP-2, compared with 18% and 13%, respectively, among controls (P less than .0001). By day 84, among treated patients, the lesion count had decreased by a mean of 69% in CAMP-1 and 83% in CAMP-2, compared with 20% and 19%, respectively, among controls. Results among controls were “probably consistent with natural history,” Dr. Eichenfield observed.
The researchers observed a high incidence of treatment-emergent adverse events among patients receiving VP-102. “Any crust or vesiculation was considered to be a treatment-emergent adverse event,” Dr. Eichenfield said. Most adverse events were mild, although five patients discontinued the studies because of treatment-emergent adverse events. Vesiculation was a common adverse event in the VP-102 group; pruritus and application-site pain were reported as well.
Verrica Pharmaceuticals developed VP-102 and funded the study. Dr. Eichenfield reported receiving no funding from the company; several other investigators are employees of Verrica, which plans to submit for FDA approval in the second half of 2019.
SOURCE: Eichenfield L et al. AAD 19, Abstract 11251.
WASHINGTON – compared with placebo, according to the results of two trials presented at the annual meeting of the American Academy of Dermatology.
VP-102, a drug-device combination, was well tolerated and was not associated with serious adverse events.
No Food and Drug Administration–approved treatment is available for treating molluscum contagiosum, which is routinely treated with cantharidin, a naturally occurring vesicant.
VP-102 is a novel formulation of 0.7% cantharidin solution, provided in a single-use applicator, to provide consistent delivery and long-term drug stability.
To test the efficacy and safety of VP-102, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and his associates conducted the CAMP-1 (Cantharidin Application in Molluscum Patients) and CAMP-2 phase 3 studies, which had similar designs. The studies enrolled patients with molluscum contagiosum aged 2 years and older who had not received any treatment in the 2 weeks before enrollment. Patients were randomized to VP-102 or vehicle for 12 weeks. Treatment was administered topically to each lesion every 3 weeks for a maximum of four applications, and washed off with soap and warm water 24 hours after application.
The trials’ primary endpoint was the percentage of patients with complete clearance of their lesions. Secondary endpoints were the percentage of patients with complete clearance at 3, 6, and 9 weeks, and decrease in lesions over time. The researchers also assessed safety and tolerability.
In the two studies, 528 patients aged 2-60 years (mean age, approximately 7 years) were randomized to treatment or vehicle. About 30% of participants had prior treatment. The baseline lesion count ranged from 1 to 184.
At day 84, the proportion of patients in the VP-102 arm who achieved complete clearance of lesions was 46% in CAMP-1 and 54% in CAMP-2, compared with 18% and 13%, respectively, among controls (P less than .0001). By day 84, among treated patients, the lesion count had decreased by a mean of 69% in CAMP-1 and 83% in CAMP-2, compared with 20% and 19%, respectively, among controls. Results among controls were “probably consistent with natural history,” Dr. Eichenfield observed.
The researchers observed a high incidence of treatment-emergent adverse events among patients receiving VP-102. “Any crust or vesiculation was considered to be a treatment-emergent adverse event,” Dr. Eichenfield said. Most adverse events were mild, although five patients discontinued the studies because of treatment-emergent adverse events. Vesiculation was a common adverse event in the VP-102 group; pruritus and application-site pain were reported as well.
Verrica Pharmaceuticals developed VP-102 and funded the study. Dr. Eichenfield reported receiving no funding from the company; several other investigators are employees of Verrica, which plans to submit for FDA approval in the second half of 2019.
SOURCE: Eichenfield L et al. AAD 19, Abstract 11251.
WASHINGTON – compared with placebo, according to the results of two trials presented at the annual meeting of the American Academy of Dermatology.
VP-102, a drug-device combination, was well tolerated and was not associated with serious adverse events.
No Food and Drug Administration–approved treatment is available for treating molluscum contagiosum, which is routinely treated with cantharidin, a naturally occurring vesicant.
VP-102 is a novel formulation of 0.7% cantharidin solution, provided in a single-use applicator, to provide consistent delivery and long-term drug stability.
To test the efficacy and safety of VP-102, Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and his associates conducted the CAMP-1 (Cantharidin Application in Molluscum Patients) and CAMP-2 phase 3 studies, which had similar designs. The studies enrolled patients with molluscum contagiosum aged 2 years and older who had not received any treatment in the 2 weeks before enrollment. Patients were randomized to VP-102 or vehicle for 12 weeks. Treatment was administered topically to each lesion every 3 weeks for a maximum of four applications, and washed off with soap and warm water 24 hours after application.
The trials’ primary endpoint was the percentage of patients with complete clearance of their lesions. Secondary endpoints were the percentage of patients with complete clearance at 3, 6, and 9 weeks, and decrease in lesions over time. The researchers also assessed safety and tolerability.
In the two studies, 528 patients aged 2-60 years (mean age, approximately 7 years) were randomized to treatment or vehicle. About 30% of participants had prior treatment. The baseline lesion count ranged from 1 to 184.
At day 84, the proportion of patients in the VP-102 arm who achieved complete clearance of lesions was 46% in CAMP-1 and 54% in CAMP-2, compared with 18% and 13%, respectively, among controls (P less than .0001). By day 84, among treated patients, the lesion count had decreased by a mean of 69% in CAMP-1 and 83% in CAMP-2, compared with 20% and 19%, respectively, among controls. Results among controls were “probably consistent with natural history,” Dr. Eichenfield observed.
The researchers observed a high incidence of treatment-emergent adverse events among patients receiving VP-102. “Any crust or vesiculation was considered to be a treatment-emergent adverse event,” Dr. Eichenfield said. Most adverse events were mild, although five patients discontinued the studies because of treatment-emergent adverse events. Vesiculation was a common adverse event in the VP-102 group; pruritus and application-site pain were reported as well.
Verrica Pharmaceuticals developed VP-102 and funded the study. Dr. Eichenfield reported receiving no funding from the company; several other investigators are employees of Verrica, which plans to submit for FDA approval in the second half of 2019.
SOURCE: Eichenfield L et al. AAD 19, Abstract 11251.
REPORTING FROM AAD 2019
Key clinical point: VP-102 is an effective treatment for molluscum contagiosum.
Major finding: In two studies, 46% and 54% of actively treated patients had complete resolution, compared with 13% and 18% of controls, respectively.
Study details: Two phase 3, randomized, double-blind, placebo-controlled trials of 528 patients with molluscum contagiosum.
Disclosures: Verrica Pharmaceuticals sponsored the study. Dr. Eichenfield reported receiving no funding from the company; several other investigators are employees of Verrica Pharmaceuticals.Source: Eichenfield L et al. AAD 19, Abstract 11251.
Up-close view of climate change proves sobering
Dr. Carl Bell steps away from American College of Psychiatrists meeting and gets a jolt
It used to be difficult to conceive of writing about climate change in light of the illnesses we psychiatrists treat. But talking about climate change has become unavoidable. Sometimes, it seems that things weigh heavy on my heart, and I have to write about them – especially when it is serious.
David Alan Pollack, MD, has been talking about climate change for some years now, and while I understood his concern, I had yet to see the psychological effects up close and personal. After all, I live in Chicago, and we are surrounded by concrete and asphalt.
Thankfully, I also travel, and I get a chance to get into nature. While in Hawaii at the American College of Psychiatrists annual meeting in February, I went snorkeling in Hanauma Bay. I saw coral and fish. The problem is I have a very vivid memories of snorkeling in that exact same nature preserve, which also was a Marine Life Conservation District in 1972 while I was attending the American Psychiatric Association annual meeting.
The contrast between the two experiences leaves me with a glum, sad, disappointed, heart-broken feeling because it was an intimate and personal experience with climate change. In 1972, I saw every type of coral imaginable: brain coral, club finger coral, elk coral, great star coral, pillar coral, staghorn coral, table coral, and tube coral. If I remember correctly, there were corky sea fingers and sea fans, but not sea turtles. In 1972, I saw bigeyefish, damselfish, doctorfish, filefish, goatfish, gobies, hogfish, lemon butterflyfish, lizardfish, parrottfish, porcupinefish, pufferfish, queen angelfish, rock beauties, sergeant majors, soldierfish, spot-tail spot-tail butterflyfish, Spanish hogfish, squirrelfish, tangs, trunkfish, or any bluehead or yellowhead wrasses.
In 2019, I saw two pieces of coral less that 9 inches in diameter and not a single sea urchin. There were maybe three types of tropical fish that I was unfamiliar with seeing. The difference between what I saw in 1972 and what I saw in 2019 was like the difference between the rain forest in Puerto Rico and the dunes of the Sahara Desert.
Sure, I have heard David talk about the mental health effects of climate change on stress, anxiety, and depression, and I have always thought that he was right. But to see climate change up close and personal is a sobering experience. I apologize to them for being part of the system and process that is destroying the planet – and leaving them with a hot mess.
At this point, it seems to me that we cannot just try to save the planet by being better stewards of our garbage and pointing out measurable indicators of climate change. We need to actively rather than passively try to save the planet. Of course, the question is who will pay for the active efforts to depollute Earth. From what I saw for myself in Hanauma Bay, I don’t think we have much time. So I am hoping that more people will take the issue of climate change seriously.
Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. Check out Dr. Bell’s new book, “Fetal Alcohol Exposure in the African-American Community,” at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community/.
Dr. Carl Bell steps away from American College of Psychiatrists meeting and gets a jolt
Dr. Carl Bell steps away from American College of Psychiatrists meeting and gets a jolt
It used to be difficult to conceive of writing about climate change in light of the illnesses we psychiatrists treat. But talking about climate change has become unavoidable. Sometimes, it seems that things weigh heavy on my heart, and I have to write about them – especially when it is serious.
David Alan Pollack, MD, has been talking about climate change for some years now, and while I understood his concern, I had yet to see the psychological effects up close and personal. After all, I live in Chicago, and we are surrounded by concrete and asphalt.
Thankfully, I also travel, and I get a chance to get into nature. While in Hawaii at the American College of Psychiatrists annual meeting in February, I went snorkeling in Hanauma Bay. I saw coral and fish. The problem is I have a very vivid memories of snorkeling in that exact same nature preserve, which also was a Marine Life Conservation District in 1972 while I was attending the American Psychiatric Association annual meeting.
The contrast between the two experiences leaves me with a glum, sad, disappointed, heart-broken feeling because it was an intimate and personal experience with climate change. In 1972, I saw every type of coral imaginable: brain coral, club finger coral, elk coral, great star coral, pillar coral, staghorn coral, table coral, and tube coral. If I remember correctly, there were corky sea fingers and sea fans, but not sea turtles. In 1972, I saw bigeyefish, damselfish, doctorfish, filefish, goatfish, gobies, hogfish, lemon butterflyfish, lizardfish, parrottfish, porcupinefish, pufferfish, queen angelfish, rock beauties, sergeant majors, soldierfish, spot-tail spot-tail butterflyfish, Spanish hogfish, squirrelfish, tangs, trunkfish, or any bluehead or yellowhead wrasses.
In 2019, I saw two pieces of coral less that 9 inches in diameter and not a single sea urchin. There were maybe three types of tropical fish that I was unfamiliar with seeing. The difference between what I saw in 1972 and what I saw in 2019 was like the difference between the rain forest in Puerto Rico and the dunes of the Sahara Desert.
Sure, I have heard David talk about the mental health effects of climate change on stress, anxiety, and depression, and I have always thought that he was right. But to see climate change up close and personal is a sobering experience. I apologize to them for being part of the system and process that is destroying the planet – and leaving them with a hot mess.
At this point, it seems to me that we cannot just try to save the planet by being better stewards of our garbage and pointing out measurable indicators of climate change. We need to actively rather than passively try to save the planet. Of course, the question is who will pay for the active efforts to depollute Earth. From what I saw for myself in Hanauma Bay, I don’t think we have much time. So I am hoping that more people will take the issue of climate change seriously.
Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. Check out Dr. Bell’s new book, “Fetal Alcohol Exposure in the African-American Community,” at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community/.
It used to be difficult to conceive of writing about climate change in light of the illnesses we psychiatrists treat. But talking about climate change has become unavoidable. Sometimes, it seems that things weigh heavy on my heart, and I have to write about them – especially when it is serious.
David Alan Pollack, MD, has been talking about climate change for some years now, and while I understood his concern, I had yet to see the psychological effects up close and personal. After all, I live in Chicago, and we are surrounded by concrete and asphalt.
Thankfully, I also travel, and I get a chance to get into nature. While in Hawaii at the American College of Psychiatrists annual meeting in February, I went snorkeling in Hanauma Bay. I saw coral and fish. The problem is I have a very vivid memories of snorkeling in that exact same nature preserve, which also was a Marine Life Conservation District in 1972 while I was attending the American Psychiatric Association annual meeting.
The contrast between the two experiences leaves me with a glum, sad, disappointed, heart-broken feeling because it was an intimate and personal experience with climate change. In 1972, I saw every type of coral imaginable: brain coral, club finger coral, elk coral, great star coral, pillar coral, staghorn coral, table coral, and tube coral. If I remember correctly, there were corky sea fingers and sea fans, but not sea turtles. In 1972, I saw bigeyefish, damselfish, doctorfish, filefish, goatfish, gobies, hogfish, lemon butterflyfish, lizardfish, parrottfish, porcupinefish, pufferfish, queen angelfish, rock beauties, sergeant majors, soldierfish, spot-tail spot-tail butterflyfish, Spanish hogfish, squirrelfish, tangs, trunkfish, or any bluehead or yellowhead wrasses.
In 2019, I saw two pieces of coral less that 9 inches in diameter and not a single sea urchin. There were maybe three types of tropical fish that I was unfamiliar with seeing. The difference between what I saw in 1972 and what I saw in 2019 was like the difference between the rain forest in Puerto Rico and the dunes of the Sahara Desert.
Sure, I have heard David talk about the mental health effects of climate change on stress, anxiety, and depression, and I have always thought that he was right. But to see climate change up close and personal is a sobering experience. I apologize to them for being part of the system and process that is destroying the planet – and leaving them with a hot mess.
At this point, it seems to me that we cannot just try to save the planet by being better stewards of our garbage and pointing out measurable indicators of climate change. We need to actively rather than passively try to save the planet. Of course, the question is who will pay for the active efforts to depollute Earth. From what I saw for myself in Hanauma Bay, I don’t think we have much time. So I am hoping that more people will take the issue of climate change seriously.
Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. Check out Dr. Bell’s new book, “Fetal Alcohol Exposure in the African-American Community,” at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community/.
A Vital Clue to the Problem
ANSWER
The correct interpretation is a bit challenging. You’ve confirmed the electrodes were placed correctly; however, the P waves are unusual (best seen in lead II) and are suggestive of an ectopic atrial rhythm. In lead II, there are two P waves for each QRS complex, consistent with second-degree atrioventricular (AV) block with 2:1 AV conduction. The QRS complex is wide at 130 ms without a right or left bundle branch pattern, consistent with a nonspecific intraventricular conduction block, and there is evidence of nonspecific ST-T wave abnormality.
These changes were new compared with the patient’s preoperative ECG, which showed sinus rhythm and no evidence of heart block.
ANSWER
The correct interpretation is a bit challenging. You’ve confirmed the electrodes were placed correctly; however, the P waves are unusual (best seen in lead II) and are suggestive of an ectopic atrial rhythm. In lead II, there are two P waves for each QRS complex, consistent with second-degree atrioventricular (AV) block with 2:1 AV conduction. The QRS complex is wide at 130 ms without a right or left bundle branch pattern, consistent with a nonspecific intraventricular conduction block, and there is evidence of nonspecific ST-T wave abnormality.
These changes were new compared with the patient’s preoperative ECG, which showed sinus rhythm and no evidence of heart block.
ANSWER
The correct interpretation is a bit challenging. You’ve confirmed the electrodes were placed correctly; however, the P waves are unusual (best seen in lead II) and are suggestive of an ectopic atrial rhythm. In lead II, there are two P waves for each QRS complex, consistent with second-degree atrioventricular (AV) block with 2:1 AV conduction. The QRS complex is wide at 130 ms without a right or left bundle branch pattern, consistent with a nonspecific intraventricular conduction block, and there is evidence of nonspecific ST-T wave abnormality.
These changes were new compared with the patient’s preoperative ECG, which showed sinus rhythm and no evidence of heart block.
Two days ago, a 76-year-old man underwent surgical repair of a left femoral fracture sustained in an automobile accident. Last night, his vital signs were concerning for asymptomatic bradycardia, prompting an order for ECG prior to morning rounds. His postoperative surgical course has been otherwise uneventful, and he is using minimal narcotic analgesia.
The patient has a long history of mild hypertension, which is well controlled with hydrochlorothiazide (50 mg/d). Otherwise, his medical history shows no angina, dyspnea, shortness of breath, or palpitations. There is no history of thyroid dysfunction or renal disease.
A pack-a-day smoker since age 15, the patient has been using a nicotine patch during his hospital stay. In the past 36 hours, he has taken 4 acetaminophen/oxycodone tablets (325/5 mg).
The patient works on a 400-acre ranch with about 100 head of cattle. His alcohol consumption was heavy until about 12 years ago, when he “blacked out” and gave up drinking altogether. He attends Alcoholics Anonymous meetings and leads sessions at his church. He denies recreational or illicit drug use.
Family history is positive for prostate cancer in his father and lung cancer in two brothers. His mother died of a hemorrhagic stroke at age 84.
The review of systems is remarkable only for discomfort due to an indwelling Foley catheter placed at the time of the surgery. He has no other specific complaints.
This morning, his vital signs include a blood pressure of 108/60 mm Hg; pulse, 42 beats/min; and O2 saturation, 100% on 2L of oxygen via nasal prongs.
When you arrive at the patient’s room, the ECG is in progress. The technician expresses concern about the tracing and shows you that the electrodes are placed properly. Looking at the ECG, you see a ventricular rate of 42 beats/min; PR interval, unmeasured; QRS duration, 130 ms; QT/QTc interval, 514/429 ms; P axis, +83°; R axis, +84°; and T axis, –43°. What is your interpretation?
