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Changing ethics of pediatric health care: The last 50 years
The ethics of pediatric health care have changed radically in the past 50 years. “History,” they say, “is written by the victors.” So, if you are not careful, you will only get part of the story. Clinical ethicists learn to seek out, involve, and empower the voices of all stakeholders. To fully appreciate how much things have changed, you must learn more than one side of the story. Indeed, piecing together the history of medical ethics reminds me of the Indian story of five blind men describing an elephant, in which each can only describe a part of an ultimately much bigger animal.
If you ask philosophers about the history of medical ethics, they will point to events 50 years ago as the beginning of the modern era. In the 1960s, physicians tended to be paternalistic authoritarians. Some considered it best not to even tell a patient that he had cancer. There was minimal patient education provided. Medications were prescribed as orders for the patient to follow. Medical research had harmed volunteers, and new protections were needed.
In 1995, the American Academy of Pediatrics Section on Bioethics emphasized the importance of obtaining the child’s assent in addition to the parent’s consent.2 Most states have passed laws permitting minors to give consent for treatment for pregnancy, sexually transmitted diseases, drug addiction, and mental health care.
Technology alters ethics
At the same time, technology has been changing medicine. New life sustaining technologies in the 1960s – such as dialysis and ventilators – created new issues of extreme financial cost, allocation of scarce resources, and even the existential question of when life ends. In 1968, an ad hoc committee at Harvard created criteria for what is colloquially called “brain death.”3 Many landmark legal cases further developed the ethics of end-of-life care.
The boundaries were even less clear at the beginning of life. Technological advances in ventilators, improvements in nursing care by neonatal intensive care unit nurses, and the whole new subspecialty of neonatology progressively lowered the gestational age for survival. The distinction between clinical care and experimental care was again blurry as neonatologists sought to overcome previously unknown complications, like retinopathy of prematurity resulting from too much oxygen and bronchopulmonary dysplasia from the ventilator. Many babies survived with profound physical and neurological compromise. The ethical dilemmas were continuously present.
Change in the status of children
There is more to the story than philosophy, law, and technology. Pediatric ethics has been profoundly impacted by a change in the status of the children. One change from 50 years ago has been the social response to child abuse.4 Norms changed. Before, fathers pretty much could raise their children any way they saw fit, including corporal punishment. Neighbors didn’t intervene. The proverb was “spare the rod and spoil the child,” but abuse was not motivated by discipline. It was cruel, authoritarian, and demeaning. The landmark article describing the Battered Child Syndrome was published in 1962.5 By 1967, the local Society for the Prevention of Cruelty to Children had become nearly obsolete, but understaffed local government agencies were just beginning to respond. In 1974, federal action produced the Child Abuse Prevention and Treatment Act.6 Medical personnel became mandatory reporters, developed expertise, and, in 2009, child abuse became a boarded subspecialty in pediatrics.
Then, in 1971, a documentary “Who Should Survive?” explored the ethical decision making for babies with birth defects.7 The harms of institutionalization became recognized. The benefits of early intervention and special education have been established. Support for an Individual Education Plan has progressed through successive laws beginning in 1975 until the Individuals with Disabilities Education Improvement Act of 2004.
This is just another example of how ethics develops from a philosophical ideal to a change in social status, followed by consciousness raising, civil rights legislation, enabling legislation, funding, and program development and implementation.
It takes a village of philosophers, activists, lawyers, legislators, physicians, and other experts to implement ethics. There are also countervailing forces. The mainstreaming of children with disabilities is one factor in the movement of children into private schools and the pressure for a voucher system, as advocated by the new Secretary of Education, Betty DeVos.
There also has been a change in the status of children as future providers. Historically, children were relied upon to provide for the parents in their old age. With decreases in infant mortality, the availability of birth control, and legalized abortions, smaller families became the social norm. Worldwide, there has been a marked drop in fertility rates in developed nations. Governmental programs such as Social Security, particularly with the introduction of Medicare in 1965, meant that the elderly were less dependent on their descendants. China found that acceptance of the One Child policy was heavily dependent on convincing parents that the State would provide for them in their old age. The modern political state has assumed duties previously performed by the family.
More recent changes
Pediatric health care is strongly impacted by public health measures. Infant mortality has been reduced by improved nutrition and public health, not medication and surgery. Mass immunization programs were viewed as an appropriate function of civic government.
The introduction of polio vaccine in the 1950s made a large impact. Families lined up at any opportunity to get the vaccine. Polio went from hundreds of thousands of cases of paralysis each summer down to zero cases of wild polio transmitted within the western hemisphere. Measles cases went from 450,000 cases a year in the early 1960s down to zero, until a fraudulent link to autism led to a significant number of parents not immunizing their children. Vaccine refusal, previously a rare ethical issue related to religious liberty, became corrupted by efforts at boutique medicine and alternative facts. In modern America, the ethics of individualism and personal rights have eclipsed civic responsibility. With herd immunity compromised, a blip up to 100 cases of measles per year was histrionically described as a huge epidemic. That spin shows ignorance of the historical record, but the risk was enough for the liberal state of California in 2015 to ban philosophical exemptions to vaccination with one of the strictest state laws in the nation.
Ethics is about values. So, as I look at the changes over 50 years, the areas that have failed to make progress are illuminating. Mental health care for children has not made the same progress achieved with vaccines and cancer therapy. My most recent clinical ethics case involved a teenager who had made a suicidal gesture by taking a handful of pills. The nurses were caught between caring for their patient and meeting the demands of an upset, authoritarian parent in a world where customer satisfaction is critical. I spent much of the night exploring hospital policy and state law. I solicited and listened to widely disparate interpretations of law, medical ethics, and hospital policy from the floor nurse, the nursing supervisor, the nursing staff on the adult inpatient psychiatric unit, three ED docs, a social worker, a government agency, and a judge’s representative. The physician of 1967 was captain of the ship and would not recognize the chaotic teamwork of modern medicine. The exercise showed me how little progress we have made in mental health care for adolescents during my 25 years of practice.
It also reminded me that I have the luxury to debate ethical minutia like vaccine hesitancy and adolescent consent in a world with Syrian refugee camps and starvation in South Sudan. Mahatma Gandhi said, “There are people in the world so hungry that God cannot appear to them except in the form of bread.” That, unfortunately, has not changed in 50 years.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. www.hhs.gov/ohrp/regulations-and-policy/belmont-report/
2. Pediatrics 1995;95:314-7.
3. JAMA. 1968;205(6):337-40.
4. Family Law Quarterly. 2008 Fall;42(3):449-63.
5. JAMA. 1962;181(1):17-24.
6. National Child Abuse and Neglect Training and Publications Project (2014). The Child Abuse Prevention and Treatment Act: 40 years of safeguarding America’s children. Washington: U.S. Department of Health and Human Services, Children’s Bureau.
7. Kennedy Inst Ethics J. 2006 Sep;16(3):205-24.
The ethics of pediatric health care have changed radically in the past 50 years. “History,” they say, “is written by the victors.” So, if you are not careful, you will only get part of the story. Clinical ethicists learn to seek out, involve, and empower the voices of all stakeholders. To fully appreciate how much things have changed, you must learn more than one side of the story. Indeed, piecing together the history of medical ethics reminds me of the Indian story of five blind men describing an elephant, in which each can only describe a part of an ultimately much bigger animal.
If you ask philosophers about the history of medical ethics, they will point to events 50 years ago as the beginning of the modern era. In the 1960s, physicians tended to be paternalistic authoritarians. Some considered it best not to even tell a patient that he had cancer. There was minimal patient education provided. Medications were prescribed as orders for the patient to follow. Medical research had harmed volunteers, and new protections were needed.
In 1995, the American Academy of Pediatrics Section on Bioethics emphasized the importance of obtaining the child’s assent in addition to the parent’s consent.2 Most states have passed laws permitting minors to give consent for treatment for pregnancy, sexually transmitted diseases, drug addiction, and mental health care.
Technology alters ethics
At the same time, technology has been changing medicine. New life sustaining technologies in the 1960s – such as dialysis and ventilators – created new issues of extreme financial cost, allocation of scarce resources, and even the existential question of when life ends. In 1968, an ad hoc committee at Harvard created criteria for what is colloquially called “brain death.”3 Many landmark legal cases further developed the ethics of end-of-life care.
The boundaries were even less clear at the beginning of life. Technological advances in ventilators, improvements in nursing care by neonatal intensive care unit nurses, and the whole new subspecialty of neonatology progressively lowered the gestational age for survival. The distinction between clinical care and experimental care was again blurry as neonatologists sought to overcome previously unknown complications, like retinopathy of prematurity resulting from too much oxygen and bronchopulmonary dysplasia from the ventilator. Many babies survived with profound physical and neurological compromise. The ethical dilemmas were continuously present.
Change in the status of children
There is more to the story than philosophy, law, and technology. Pediatric ethics has been profoundly impacted by a change in the status of the children. One change from 50 years ago has been the social response to child abuse.4 Norms changed. Before, fathers pretty much could raise their children any way they saw fit, including corporal punishment. Neighbors didn’t intervene. The proverb was “spare the rod and spoil the child,” but abuse was not motivated by discipline. It was cruel, authoritarian, and demeaning. The landmark article describing the Battered Child Syndrome was published in 1962.5 By 1967, the local Society for the Prevention of Cruelty to Children had become nearly obsolete, but understaffed local government agencies were just beginning to respond. In 1974, federal action produced the Child Abuse Prevention and Treatment Act.6 Medical personnel became mandatory reporters, developed expertise, and, in 2009, child abuse became a boarded subspecialty in pediatrics.
Then, in 1971, a documentary “Who Should Survive?” explored the ethical decision making for babies with birth defects.7 The harms of institutionalization became recognized. The benefits of early intervention and special education have been established. Support for an Individual Education Plan has progressed through successive laws beginning in 1975 until the Individuals with Disabilities Education Improvement Act of 2004.
This is just another example of how ethics develops from a philosophical ideal to a change in social status, followed by consciousness raising, civil rights legislation, enabling legislation, funding, and program development and implementation.
It takes a village of philosophers, activists, lawyers, legislators, physicians, and other experts to implement ethics. There are also countervailing forces. The mainstreaming of children with disabilities is one factor in the movement of children into private schools and the pressure for a voucher system, as advocated by the new Secretary of Education, Betty DeVos.
There also has been a change in the status of children as future providers. Historically, children were relied upon to provide for the parents in their old age. With decreases in infant mortality, the availability of birth control, and legalized abortions, smaller families became the social norm. Worldwide, there has been a marked drop in fertility rates in developed nations. Governmental programs such as Social Security, particularly with the introduction of Medicare in 1965, meant that the elderly were less dependent on their descendants. China found that acceptance of the One Child policy was heavily dependent on convincing parents that the State would provide for them in their old age. The modern political state has assumed duties previously performed by the family.
More recent changes
Pediatric health care is strongly impacted by public health measures. Infant mortality has been reduced by improved nutrition and public health, not medication and surgery. Mass immunization programs were viewed as an appropriate function of civic government.
The introduction of polio vaccine in the 1950s made a large impact. Families lined up at any opportunity to get the vaccine. Polio went from hundreds of thousands of cases of paralysis each summer down to zero cases of wild polio transmitted within the western hemisphere. Measles cases went from 450,000 cases a year in the early 1960s down to zero, until a fraudulent link to autism led to a significant number of parents not immunizing their children. Vaccine refusal, previously a rare ethical issue related to religious liberty, became corrupted by efforts at boutique medicine and alternative facts. In modern America, the ethics of individualism and personal rights have eclipsed civic responsibility. With herd immunity compromised, a blip up to 100 cases of measles per year was histrionically described as a huge epidemic. That spin shows ignorance of the historical record, but the risk was enough for the liberal state of California in 2015 to ban philosophical exemptions to vaccination with one of the strictest state laws in the nation.
Ethics is about values. So, as I look at the changes over 50 years, the areas that have failed to make progress are illuminating. Mental health care for children has not made the same progress achieved with vaccines and cancer therapy. My most recent clinical ethics case involved a teenager who had made a suicidal gesture by taking a handful of pills. The nurses were caught between caring for their patient and meeting the demands of an upset, authoritarian parent in a world where customer satisfaction is critical. I spent much of the night exploring hospital policy and state law. I solicited and listened to widely disparate interpretations of law, medical ethics, and hospital policy from the floor nurse, the nursing supervisor, the nursing staff on the adult inpatient psychiatric unit, three ED docs, a social worker, a government agency, and a judge’s representative. The physician of 1967 was captain of the ship and would not recognize the chaotic teamwork of modern medicine. The exercise showed me how little progress we have made in mental health care for adolescents during my 25 years of practice.
It also reminded me that I have the luxury to debate ethical minutia like vaccine hesitancy and adolescent consent in a world with Syrian refugee camps and starvation in South Sudan. Mahatma Gandhi said, “There are people in the world so hungry that God cannot appear to them except in the form of bread.” That, unfortunately, has not changed in 50 years.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. www.hhs.gov/ohrp/regulations-and-policy/belmont-report/
2. Pediatrics 1995;95:314-7.
3. JAMA. 1968;205(6):337-40.
4. Family Law Quarterly. 2008 Fall;42(3):449-63.
5. JAMA. 1962;181(1):17-24.
6. National Child Abuse and Neglect Training and Publications Project (2014). The Child Abuse Prevention and Treatment Act: 40 years of safeguarding America’s children. Washington: U.S. Department of Health and Human Services, Children’s Bureau.
7. Kennedy Inst Ethics J. 2006 Sep;16(3):205-24.
The ethics of pediatric health care have changed radically in the past 50 years. “History,” they say, “is written by the victors.” So, if you are not careful, you will only get part of the story. Clinical ethicists learn to seek out, involve, and empower the voices of all stakeholders. To fully appreciate how much things have changed, you must learn more than one side of the story. Indeed, piecing together the history of medical ethics reminds me of the Indian story of five blind men describing an elephant, in which each can only describe a part of an ultimately much bigger animal.
If you ask philosophers about the history of medical ethics, they will point to events 50 years ago as the beginning of the modern era. In the 1960s, physicians tended to be paternalistic authoritarians. Some considered it best not to even tell a patient that he had cancer. There was minimal patient education provided. Medications were prescribed as orders for the patient to follow. Medical research had harmed volunteers, and new protections were needed.
In 1995, the American Academy of Pediatrics Section on Bioethics emphasized the importance of obtaining the child’s assent in addition to the parent’s consent.2 Most states have passed laws permitting minors to give consent for treatment for pregnancy, sexually transmitted diseases, drug addiction, and mental health care.
Technology alters ethics
At the same time, technology has been changing medicine. New life sustaining technologies in the 1960s – such as dialysis and ventilators – created new issues of extreme financial cost, allocation of scarce resources, and even the existential question of when life ends. In 1968, an ad hoc committee at Harvard created criteria for what is colloquially called “brain death.”3 Many landmark legal cases further developed the ethics of end-of-life care.
The boundaries were even less clear at the beginning of life. Technological advances in ventilators, improvements in nursing care by neonatal intensive care unit nurses, and the whole new subspecialty of neonatology progressively lowered the gestational age for survival. The distinction between clinical care and experimental care was again blurry as neonatologists sought to overcome previously unknown complications, like retinopathy of prematurity resulting from too much oxygen and bronchopulmonary dysplasia from the ventilator. Many babies survived with profound physical and neurological compromise. The ethical dilemmas were continuously present.
Change in the status of children
There is more to the story than philosophy, law, and technology. Pediatric ethics has been profoundly impacted by a change in the status of the children. One change from 50 years ago has been the social response to child abuse.4 Norms changed. Before, fathers pretty much could raise their children any way they saw fit, including corporal punishment. Neighbors didn’t intervene. The proverb was “spare the rod and spoil the child,” but abuse was not motivated by discipline. It was cruel, authoritarian, and demeaning. The landmark article describing the Battered Child Syndrome was published in 1962.5 By 1967, the local Society for the Prevention of Cruelty to Children had become nearly obsolete, but understaffed local government agencies were just beginning to respond. In 1974, federal action produced the Child Abuse Prevention and Treatment Act.6 Medical personnel became mandatory reporters, developed expertise, and, in 2009, child abuse became a boarded subspecialty in pediatrics.
Then, in 1971, a documentary “Who Should Survive?” explored the ethical decision making for babies with birth defects.7 The harms of institutionalization became recognized. The benefits of early intervention and special education have been established. Support for an Individual Education Plan has progressed through successive laws beginning in 1975 until the Individuals with Disabilities Education Improvement Act of 2004.
This is just another example of how ethics develops from a philosophical ideal to a change in social status, followed by consciousness raising, civil rights legislation, enabling legislation, funding, and program development and implementation.
It takes a village of philosophers, activists, lawyers, legislators, physicians, and other experts to implement ethics. There are also countervailing forces. The mainstreaming of children with disabilities is one factor in the movement of children into private schools and the pressure for a voucher system, as advocated by the new Secretary of Education, Betty DeVos.
There also has been a change in the status of children as future providers. Historically, children were relied upon to provide for the parents in their old age. With decreases in infant mortality, the availability of birth control, and legalized abortions, smaller families became the social norm. Worldwide, there has been a marked drop in fertility rates in developed nations. Governmental programs such as Social Security, particularly with the introduction of Medicare in 1965, meant that the elderly were less dependent on their descendants. China found that acceptance of the One Child policy was heavily dependent on convincing parents that the State would provide for them in their old age. The modern political state has assumed duties previously performed by the family.
More recent changes
Pediatric health care is strongly impacted by public health measures. Infant mortality has been reduced by improved nutrition and public health, not medication and surgery. Mass immunization programs were viewed as an appropriate function of civic government.
The introduction of polio vaccine in the 1950s made a large impact. Families lined up at any opportunity to get the vaccine. Polio went from hundreds of thousands of cases of paralysis each summer down to zero cases of wild polio transmitted within the western hemisphere. Measles cases went from 450,000 cases a year in the early 1960s down to zero, until a fraudulent link to autism led to a significant number of parents not immunizing their children. Vaccine refusal, previously a rare ethical issue related to religious liberty, became corrupted by efforts at boutique medicine and alternative facts. In modern America, the ethics of individualism and personal rights have eclipsed civic responsibility. With herd immunity compromised, a blip up to 100 cases of measles per year was histrionically described as a huge epidemic. That spin shows ignorance of the historical record, but the risk was enough for the liberal state of California in 2015 to ban philosophical exemptions to vaccination with one of the strictest state laws in the nation.
Ethics is about values. So, as I look at the changes over 50 years, the areas that have failed to make progress are illuminating. Mental health care for children has not made the same progress achieved with vaccines and cancer therapy. My most recent clinical ethics case involved a teenager who had made a suicidal gesture by taking a handful of pills. The nurses were caught between caring for their patient and meeting the demands of an upset, authoritarian parent in a world where customer satisfaction is critical. I spent much of the night exploring hospital policy and state law. I solicited and listened to widely disparate interpretations of law, medical ethics, and hospital policy from the floor nurse, the nursing supervisor, the nursing staff on the adult inpatient psychiatric unit, three ED docs, a social worker, a government agency, and a judge’s representative. The physician of 1967 was captain of the ship and would not recognize the chaotic teamwork of modern medicine. The exercise showed me how little progress we have made in mental health care for adolescents during my 25 years of practice.
It also reminded me that I have the luxury to debate ethical minutia like vaccine hesitancy and adolescent consent in a world with Syrian refugee camps and starvation in South Sudan. Mahatma Gandhi said, “There are people in the world so hungry that God cannot appear to them except in the form of bread.” That, unfortunately, has not changed in 50 years.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. www.hhs.gov/ohrp/regulations-and-policy/belmont-report/
2. Pediatrics 1995;95:314-7.
3. JAMA. 1968;205(6):337-40.
4. Family Law Quarterly. 2008 Fall;42(3):449-63.
5. JAMA. 1962;181(1):17-24.
6. National Child Abuse and Neglect Training and Publications Project (2014). The Child Abuse Prevention and Treatment Act: 40 years of safeguarding America’s children. Washington: U.S. Department of Health and Human Services, Children’s Bureau.
7. Kennedy Inst Ethics J. 2006 Sep;16(3):205-24.
Second generation ALK inhibitors show good response in second-line NSCLC
GENEVA – Second-generation inhibitors of the anaplastic lymphoma kinase (ALK) are associated with high response rates in patients with non–small cell lung cancer (NSCLC) who have disease progression after treatment with the first-generation ALK inhibitor crizotinib (Xalkori), investigators reported.
Of 117 patients with ALK-positive NSCLC that progressed while on treatment with the ALK-targeting tyrosine-kinase inhibitor (TKI) crizotinib, both ceritinib (Zykadia) and alectinib (Alecensa) were associated with high combined partial and complete response rates, reported Christian Britschgi, MD, PhD, of University Hospital Zürich, and his colleagues.
“We can confirm the high rate of response of ceritinib and alectinib as second TKIs,” Dr. Britschgi said in an interview.
“With ceritinib or alectinib in the first line, however, it’s hard to draw any conclusions because there are very few patients treated with these drugs in the first line who were included in the trials,” he added.
ALK rearrangements occur in 3%-5% of lung adenocarcinomas, and these mutations are potential targets for TKIs directed against ALK.
The investigators analyzed the clinical characteristics of response to, and disease progression on, available ALK-TKIs. They also performed next-generation sequencing on a small group of tumor samples to investigate mechanisms of resistance and to look for new mutations that could be targetable.
They collected data on patients with ALK-positive NSCLC who were receiving palliative care and looked at clinical data and biopsy samples collected before treatment, and where available, post–ALK-TKI therapy.
They collected clinical data on 139 patients, 117 of whom had undergone first-line treatment with chemotherapy (74%), ALK-TKIs (25%), or other therapies (1%). Of this group, 92 received second-line therapy – chemotherapy (17%), ALK-TKIs (74%), or immunotherapies/other (9%).
Third-line treatments were given to 55 patients, 20% of whom received chemotherapy, 75% of whom received ALK-TKIs, and 5% of whom received other therapies.
Twenty-four patients survived long enough to receive fourth-line treatments, which included chemotherapy in 8 patients (33%), ALK-TKIs in 15 (63%), or other therapies in 1 patient.
In all, 102 patients received crizotinib, all but one in the first line and the remaining patient in the second line. The overall response rate was 58.8% (59.4% for the 101 first-line patients). Median progression-free survival (PFS) in these patients was 11.7 months.
Ceritinib was given to 2 patients in the first line, 7 in the second line, and 28 in the third line. The overall response rate was 48.6% (50% in the two patients who received it in the first line, and 50% in patients who received it after crizotinib). The median PFS was 6.5 months.
For the 26 patients who received alectinib – 3 in the first line and 23 after crizotinib – the overall response rate was 100% when the drug was used in the first line, and 60.9% when used in the second and subsequent lines. Median PFS was 12.4 months.
Only a few patients to date have had next-generation sequencing of tumors performed, Dr. Britschgi said. One patient who developed resistance while on alectinib was found to have a point mutation (ALK p.lle117Ser) that was not found in a pretreatment biopsy sample, indicating that it had emerged during therapy. This patient was then started on and had a response to lorlatinib.
A second patient who had received several lines of therapy including chemotherapy and TKIs and was enrolled in the expanded access program for lorlatinib developed hepatic progression while on that drug. A biopsy showed that the tumor carried epidermal growth-factor receptor variant 3, which is known to be highly mutagenic and is associated with glioblastoma. The patient was then put on nivolumab (Opdivo) and had a good response, but had further progression, and was then put on alectinib and again had a good response that is currently ongoing, Dr. Britschgi said.
The study was supported by University Hospital Zurich and Novartis. Dr. Britschgi reported no relevant disclosures. Coauthor Sacha Rothschild, MD, PhD, disclosed institutional compensation for advisory boards from Novartis, Pfizer and Roche.
GENEVA – Second-generation inhibitors of the anaplastic lymphoma kinase (ALK) are associated with high response rates in patients with non–small cell lung cancer (NSCLC) who have disease progression after treatment with the first-generation ALK inhibitor crizotinib (Xalkori), investigators reported.
Of 117 patients with ALK-positive NSCLC that progressed while on treatment with the ALK-targeting tyrosine-kinase inhibitor (TKI) crizotinib, both ceritinib (Zykadia) and alectinib (Alecensa) were associated with high combined partial and complete response rates, reported Christian Britschgi, MD, PhD, of University Hospital Zürich, and his colleagues.
“We can confirm the high rate of response of ceritinib and alectinib as second TKIs,” Dr. Britschgi said in an interview.
“With ceritinib or alectinib in the first line, however, it’s hard to draw any conclusions because there are very few patients treated with these drugs in the first line who were included in the trials,” he added.
ALK rearrangements occur in 3%-5% of lung adenocarcinomas, and these mutations are potential targets for TKIs directed against ALK.
The investigators analyzed the clinical characteristics of response to, and disease progression on, available ALK-TKIs. They also performed next-generation sequencing on a small group of tumor samples to investigate mechanisms of resistance and to look for new mutations that could be targetable.
They collected data on patients with ALK-positive NSCLC who were receiving palliative care and looked at clinical data and biopsy samples collected before treatment, and where available, post–ALK-TKI therapy.
They collected clinical data on 139 patients, 117 of whom had undergone first-line treatment with chemotherapy (74%), ALK-TKIs (25%), or other therapies (1%). Of this group, 92 received second-line therapy – chemotherapy (17%), ALK-TKIs (74%), or immunotherapies/other (9%).
Third-line treatments were given to 55 patients, 20% of whom received chemotherapy, 75% of whom received ALK-TKIs, and 5% of whom received other therapies.
Twenty-four patients survived long enough to receive fourth-line treatments, which included chemotherapy in 8 patients (33%), ALK-TKIs in 15 (63%), or other therapies in 1 patient.
In all, 102 patients received crizotinib, all but one in the first line and the remaining patient in the second line. The overall response rate was 58.8% (59.4% for the 101 first-line patients). Median progression-free survival (PFS) in these patients was 11.7 months.
Ceritinib was given to 2 patients in the first line, 7 in the second line, and 28 in the third line. The overall response rate was 48.6% (50% in the two patients who received it in the first line, and 50% in patients who received it after crizotinib). The median PFS was 6.5 months.
For the 26 patients who received alectinib – 3 in the first line and 23 after crizotinib – the overall response rate was 100% when the drug was used in the first line, and 60.9% when used in the second and subsequent lines. Median PFS was 12.4 months.
Only a few patients to date have had next-generation sequencing of tumors performed, Dr. Britschgi said. One patient who developed resistance while on alectinib was found to have a point mutation (ALK p.lle117Ser) that was not found in a pretreatment biopsy sample, indicating that it had emerged during therapy. This patient was then started on and had a response to lorlatinib.
A second patient who had received several lines of therapy including chemotherapy and TKIs and was enrolled in the expanded access program for lorlatinib developed hepatic progression while on that drug. A biopsy showed that the tumor carried epidermal growth-factor receptor variant 3, which is known to be highly mutagenic and is associated with glioblastoma. The patient was then put on nivolumab (Opdivo) and had a good response, but had further progression, and was then put on alectinib and again had a good response that is currently ongoing, Dr. Britschgi said.
The study was supported by University Hospital Zurich and Novartis. Dr. Britschgi reported no relevant disclosures. Coauthor Sacha Rothschild, MD, PhD, disclosed institutional compensation for advisory boards from Novartis, Pfizer and Roche.
GENEVA – Second-generation inhibitors of the anaplastic lymphoma kinase (ALK) are associated with high response rates in patients with non–small cell lung cancer (NSCLC) who have disease progression after treatment with the first-generation ALK inhibitor crizotinib (Xalkori), investigators reported.
Of 117 patients with ALK-positive NSCLC that progressed while on treatment with the ALK-targeting tyrosine-kinase inhibitor (TKI) crizotinib, both ceritinib (Zykadia) and alectinib (Alecensa) were associated with high combined partial and complete response rates, reported Christian Britschgi, MD, PhD, of University Hospital Zürich, and his colleagues.
“We can confirm the high rate of response of ceritinib and alectinib as second TKIs,” Dr. Britschgi said in an interview.
“With ceritinib or alectinib in the first line, however, it’s hard to draw any conclusions because there are very few patients treated with these drugs in the first line who were included in the trials,” he added.
ALK rearrangements occur in 3%-5% of lung adenocarcinomas, and these mutations are potential targets for TKIs directed against ALK.
The investigators analyzed the clinical characteristics of response to, and disease progression on, available ALK-TKIs. They also performed next-generation sequencing on a small group of tumor samples to investigate mechanisms of resistance and to look for new mutations that could be targetable.
They collected data on patients with ALK-positive NSCLC who were receiving palliative care and looked at clinical data and biopsy samples collected before treatment, and where available, post–ALK-TKI therapy.
They collected clinical data on 139 patients, 117 of whom had undergone first-line treatment with chemotherapy (74%), ALK-TKIs (25%), or other therapies (1%). Of this group, 92 received second-line therapy – chemotherapy (17%), ALK-TKIs (74%), or immunotherapies/other (9%).
Third-line treatments were given to 55 patients, 20% of whom received chemotherapy, 75% of whom received ALK-TKIs, and 5% of whom received other therapies.
Twenty-four patients survived long enough to receive fourth-line treatments, which included chemotherapy in 8 patients (33%), ALK-TKIs in 15 (63%), or other therapies in 1 patient.
In all, 102 patients received crizotinib, all but one in the first line and the remaining patient in the second line. The overall response rate was 58.8% (59.4% for the 101 first-line patients). Median progression-free survival (PFS) in these patients was 11.7 months.
Ceritinib was given to 2 patients in the first line, 7 in the second line, and 28 in the third line. The overall response rate was 48.6% (50% in the two patients who received it in the first line, and 50% in patients who received it after crizotinib). The median PFS was 6.5 months.
For the 26 patients who received alectinib – 3 in the first line and 23 after crizotinib – the overall response rate was 100% when the drug was used in the first line, and 60.9% when used in the second and subsequent lines. Median PFS was 12.4 months.
Only a few patients to date have had next-generation sequencing of tumors performed, Dr. Britschgi said. One patient who developed resistance while on alectinib was found to have a point mutation (ALK p.lle117Ser) that was not found in a pretreatment biopsy sample, indicating that it had emerged during therapy. This patient was then started on and had a response to lorlatinib.
A second patient who had received several lines of therapy including chemotherapy and TKIs and was enrolled in the expanded access program for lorlatinib developed hepatic progression while on that drug. A biopsy showed that the tumor carried epidermal growth-factor receptor variant 3, which is known to be highly mutagenic and is associated with glioblastoma. The patient was then put on nivolumab (Opdivo) and had a good response, but had further progression, and was then put on alectinib and again had a good response that is currently ongoing, Dr. Britschgi said.
The study was supported by University Hospital Zurich and Novartis. Dr. Britschgi reported no relevant disclosures. Coauthor Sacha Rothschild, MD, PhD, disclosed institutional compensation for advisory boards from Novartis, Pfizer and Roche.
FROM ELCC
Key clinical point:
Major finding: Overall response rates after crizotinib were 50% for ceritinib and 60.9% for alectinib.
Data source: A retrospective review of data on 117 patients with ALK-positive NSCLC in Swiss and Italian hospitals.
Disclosures: The study was supported by University Hospital Zurich and Novartis. Dr. Britschgi reported no relevant disclosures. Coauthor Sacha Rothschild, MD, PhD, disclosed institutional compensation for advisory boards from Novartis, Pfizer, and Roche.
FDA: Fluoroquinolone use not linked to retina detachment, aortic problems
The Food and Drug Administration has found no evidence of a link between fluoroquinolone usage and retinal detachment or aortic aneurysm and dissection, according to a new Drug Safety Communication update on potential serious, disabling side effects of oral and injectable fluoroquinolone antibiotics.
Fluoroquinolones are used to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections.
However, after reviewing patient cases and study findings, the FDA said the evidence didn’t support an association between fluoroquinolone usage and potential retinal or aortic dangers, according to its May 10, 2017, Drug Safety Communication update.
Serious side effects associated with fluoroquinolone use include hallucination, depression, suicidal thoughts, tendinitis and tendon rupture, a “pins and needles” feeling in the arms and legs, joint pain and swelling, skin rash, and severe diarrhea.
“We will continue to assess safety issues with fluoroquinolones, and will update the public if additional actions are needed,” the FDA said in a statement.
The Food and Drug Administration has found no evidence of a link between fluoroquinolone usage and retinal detachment or aortic aneurysm and dissection, according to a new Drug Safety Communication update on potential serious, disabling side effects of oral and injectable fluoroquinolone antibiotics.
Fluoroquinolones are used to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections.
However, after reviewing patient cases and study findings, the FDA said the evidence didn’t support an association between fluoroquinolone usage and potential retinal or aortic dangers, according to its May 10, 2017, Drug Safety Communication update.
Serious side effects associated with fluoroquinolone use include hallucination, depression, suicidal thoughts, tendinitis and tendon rupture, a “pins and needles” feeling in the arms and legs, joint pain and swelling, skin rash, and severe diarrhea.
“We will continue to assess safety issues with fluoroquinolones, and will update the public if additional actions are needed,” the FDA said in a statement.
The Food and Drug Administration has found no evidence of a link between fluoroquinolone usage and retinal detachment or aortic aneurysm and dissection, according to a new Drug Safety Communication update on potential serious, disabling side effects of oral and injectable fluoroquinolone antibiotics.
Fluoroquinolones are used to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections.
However, after reviewing patient cases and study findings, the FDA said the evidence didn’t support an association between fluoroquinolone usage and potential retinal or aortic dangers, according to its May 10, 2017, Drug Safety Communication update.
Serious side effects associated with fluoroquinolone use include hallucination, depression, suicidal thoughts, tendinitis and tendon rupture, a “pins and needles” feeling in the arms and legs, joint pain and swelling, skin rash, and severe diarrhea.
“We will continue to assess safety issues with fluoroquinolones, and will update the public if additional actions are needed,” the FDA said in a statement.
SLE linked to subsequent risk of malignant melanoma
PORTLAND, ORE. – A diagnosis of systemic lupus erythematosus (SLE) significantly increases the risk of a subsequent diagnosis of malignant melanoma, according to the results of a large, first-in-kind, single-center longitudinal analysis of electronic medical records.
This finding expands the list of known associations between SLE and cancer, and highlights the need for careful surveillance of this population, Solomiya Grushchak, of the department of dermatology at Northwestern University, Chicago, and her associates, reported in a poster presented at the annual meeting of the Society for Investigative Dermatology.
SLE is increasingly being treated with immune checkpoint inhibitors, which can aggressively disrupt immune reactivity and trigger uncontrolled cellular responses in patients with SLE, Ms. Grushchak noted. “The findings in this large population warrant further exploration of the association between malignant melanoma and SLE to promote optimal patient management, especially in light of recent advances [in the use of] checkpoint inhibitors,” she added.
Past work has linked SLE with several other malignancies, including nonmelanoma skin cancers, non-Hodgkin and Hodgkin lymphomas, and cancers of the larynx, lungs, liver, vulva, vagina, and thyroid gland. Even when patients are not receiving checkpoint inhibitors, SLE causes chronic inflammation and is known to increase cellular dysplasia, which can ultimately trigger uncontrolled proliferation of tumor cells. In 2015, a meta-analysis showed that SLE was associated with a decreased risk of melanoma, but no studies had conclusively evaluated this relationship (PLoS One. 2015;10[4]:e0122964).
Therefore, Ms. Grushchak and her associates analyzed medical records from 2,351 patients from the urban Midwest with SLE diagnosed by a dermatologist or rheumatologist between 2000 and 2016. The data source was the Northwestern Enterprise Data Warehouse, which integrates clinical and research information from more than 50 health data systems used by the Northwestern University Feinberg School of Medicine and its health care partners. To avoid detection bias, the researchers constructed a comparison group from the same database of 1,676 patients diagnosed with systemic sclerosis.
Ten patients (0.4%) with a diagnostic code for SLE were later diagnosed with malignant melanoma, compared with one patient with systemic sclerosis (0.06%), the investigators reported. A Fisher’s exact test confirmed a statistically significant difference between these rates (P = .03). Among the 10 SLE patients with melanoma, 7 were white, 2 were black, and 1 was of Asian ancestry. Nine were females, and one was male. The patient with systemic sclerosis and melanoma was a white male.
The study had several limitations. The investigators did not report how much time elapsed between the diagnoses of SLE and melanoma, or the rates or cumulative exposure to checkpoint inhibitors.
The National Institutes of Health provides support to the Northwestern Enterprise Data Warehouse. The investigators had no relevant financial conflicts.
PORTLAND, ORE. – A diagnosis of systemic lupus erythematosus (SLE) significantly increases the risk of a subsequent diagnosis of malignant melanoma, according to the results of a large, first-in-kind, single-center longitudinal analysis of electronic medical records.
This finding expands the list of known associations between SLE and cancer, and highlights the need for careful surveillance of this population, Solomiya Grushchak, of the department of dermatology at Northwestern University, Chicago, and her associates, reported in a poster presented at the annual meeting of the Society for Investigative Dermatology.
SLE is increasingly being treated with immune checkpoint inhibitors, which can aggressively disrupt immune reactivity and trigger uncontrolled cellular responses in patients with SLE, Ms. Grushchak noted. “The findings in this large population warrant further exploration of the association between malignant melanoma and SLE to promote optimal patient management, especially in light of recent advances [in the use of] checkpoint inhibitors,” she added.
Past work has linked SLE with several other malignancies, including nonmelanoma skin cancers, non-Hodgkin and Hodgkin lymphomas, and cancers of the larynx, lungs, liver, vulva, vagina, and thyroid gland. Even when patients are not receiving checkpoint inhibitors, SLE causes chronic inflammation and is known to increase cellular dysplasia, which can ultimately trigger uncontrolled proliferation of tumor cells. In 2015, a meta-analysis showed that SLE was associated with a decreased risk of melanoma, but no studies had conclusively evaluated this relationship (PLoS One. 2015;10[4]:e0122964).
Therefore, Ms. Grushchak and her associates analyzed medical records from 2,351 patients from the urban Midwest with SLE diagnosed by a dermatologist or rheumatologist between 2000 and 2016. The data source was the Northwestern Enterprise Data Warehouse, which integrates clinical and research information from more than 50 health data systems used by the Northwestern University Feinberg School of Medicine and its health care partners. To avoid detection bias, the researchers constructed a comparison group from the same database of 1,676 patients diagnosed with systemic sclerosis.
Ten patients (0.4%) with a diagnostic code for SLE were later diagnosed with malignant melanoma, compared with one patient with systemic sclerosis (0.06%), the investigators reported. A Fisher’s exact test confirmed a statistically significant difference between these rates (P = .03). Among the 10 SLE patients with melanoma, 7 were white, 2 were black, and 1 was of Asian ancestry. Nine were females, and one was male. The patient with systemic sclerosis and melanoma was a white male.
The study had several limitations. The investigators did not report how much time elapsed between the diagnoses of SLE and melanoma, or the rates or cumulative exposure to checkpoint inhibitors.
The National Institutes of Health provides support to the Northwestern Enterprise Data Warehouse. The investigators had no relevant financial conflicts.
PORTLAND, ORE. – A diagnosis of systemic lupus erythematosus (SLE) significantly increases the risk of a subsequent diagnosis of malignant melanoma, according to the results of a large, first-in-kind, single-center longitudinal analysis of electronic medical records.
This finding expands the list of known associations between SLE and cancer, and highlights the need for careful surveillance of this population, Solomiya Grushchak, of the department of dermatology at Northwestern University, Chicago, and her associates, reported in a poster presented at the annual meeting of the Society for Investigative Dermatology.
SLE is increasingly being treated with immune checkpoint inhibitors, which can aggressively disrupt immune reactivity and trigger uncontrolled cellular responses in patients with SLE, Ms. Grushchak noted. “The findings in this large population warrant further exploration of the association between malignant melanoma and SLE to promote optimal patient management, especially in light of recent advances [in the use of] checkpoint inhibitors,” she added.
Past work has linked SLE with several other malignancies, including nonmelanoma skin cancers, non-Hodgkin and Hodgkin lymphomas, and cancers of the larynx, lungs, liver, vulva, vagina, and thyroid gland. Even when patients are not receiving checkpoint inhibitors, SLE causes chronic inflammation and is known to increase cellular dysplasia, which can ultimately trigger uncontrolled proliferation of tumor cells. In 2015, a meta-analysis showed that SLE was associated with a decreased risk of melanoma, but no studies had conclusively evaluated this relationship (PLoS One. 2015;10[4]:e0122964).
Therefore, Ms. Grushchak and her associates analyzed medical records from 2,351 patients from the urban Midwest with SLE diagnosed by a dermatologist or rheumatologist between 2000 and 2016. The data source was the Northwestern Enterprise Data Warehouse, which integrates clinical and research information from more than 50 health data systems used by the Northwestern University Feinberg School of Medicine and its health care partners. To avoid detection bias, the researchers constructed a comparison group from the same database of 1,676 patients diagnosed with systemic sclerosis.
Ten patients (0.4%) with a diagnostic code for SLE were later diagnosed with malignant melanoma, compared with one patient with systemic sclerosis (0.06%), the investigators reported. A Fisher’s exact test confirmed a statistically significant difference between these rates (P = .03). Among the 10 SLE patients with melanoma, 7 were white, 2 were black, and 1 was of Asian ancestry. Nine were females, and one was male. The patient with systemic sclerosis and melanoma was a white male.
The study had several limitations. The investigators did not report how much time elapsed between the diagnoses of SLE and melanoma, or the rates or cumulative exposure to checkpoint inhibitors.
The National Institutes of Health provides support to the Northwestern Enterprise Data Warehouse. The investigators had no relevant financial conflicts.
AT SID 2017
Key clinical point: Compared with controls, patients with systemic lupus erythematosus (SLE) were at significantly increased risk of later being diagnosed with malignant melanoma.
Major finding: Ten patients with SLE (0.4%) were later diagnosed with malignant melanoma, compared with one patient with systemic sclerosis (0.06%), a statistically significant difference (P = .03).
Data source: Electronic medical record reviews of 2,351 patients with SLE and 1,676 patients with systemic sclerosis (controls) between 2000 and 2016.
Disclosures: The National Institutes of Health provides support to the Northwestern Enterprise Data Warehouse. The investigators had no relevant financial conflicts.
Contact dermatitis in children: The top 10 allergens
Contact dermatitis should be suspected in patients with eczematous dermatitis atypical in location, geometric or symmetric in distribution, or unresponsive to or worsened by common therapies, Dr. Catalina Matiz emphasized.
Allergic contact dermatitis is a complex disorder characterized by a type IV delayed-type hypersensitivity reaction that occurs when a patient’s skin is exposed to a substance easily penetrates the skin barrier.
Increasingly recognized in the United States, many pediatric patients are becoming sensitized to contact allergens found in personal care products, including skin care products, topical medications, and clothing.
A study published by Hill et al. in 2016 reviewed pediatric patch test studies to determine the top contact allergens in children (Expert Rev Clin Immunol. 2016;12[5]:551-61).
Dr. Matiz presented the top 10 allergens discovered by this group, and offered practical advice for allergen avoidance.
Topping the list in descending order are the following:
- Tixocortol pivalate (a corticosteroid).
- Propylene glycol.
- Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI).
- Formaldehyde.
- Cocamidopropyl betaine.
- Lanolin.
- Benzalkonium chloride.
- Fragrance and balsam of peru.
- Neomycin.
- Nickel.
Dr. Matiz educated meeting attendees on allergen-containing products and clinical correlations suggestive of allergic sensitization to common allergens. Tixocortol pivilate is a corticosteroid present in Class A corticosteroids including hydrocortisone acetate. She highlighted the cross reactivity between class A and class D2 corticosteroids including hydrocortisone butyrate and valerate.
“Usually topical corticosteroid–contact sensitivity manifests as a failure to improve or worsening of existing dermatitis,” emphasized Dr. Matiz of departments of dermatology and pediatrics at the university.
Propylene glycol, benzalkonium chloride, and neomycin also represent top contact allergens frequently found in topical medications. Similarly, lanolin contact sensitivity often presents as refractory or worsening atopic dermatitis. “Lanolin, also known as wool alcohol, is commonly found in emollients, medications, and personal care products used by atopic dermatitis patients,” Dr. Matiz stressed.
Methylchloroisothiazolinone/methylisothiazolinone represent preservatives commonly found in wet wipes, hypoallergenic, and sensitive skin products. This was the allergen of the year in 2013 and was subsequently removed from many wet wipe formulations and products in response.
In addition to acute management of allergic contact dermatitis with corticosteroids, Dr. Matiz further emphasized the importance of preemptive avoidance of the top ten allergens.
She recommends patch testing if no clinical improvement is evident after 8 weeks of common allergen avoidance, for definitive allergen identification.
Dr. Matiz said she had no relevant financial disclosures.
Contact dermatitis should be suspected in patients with eczematous dermatitis atypical in location, geometric or symmetric in distribution, or unresponsive to or worsened by common therapies, Dr. Catalina Matiz emphasized.
Allergic contact dermatitis is a complex disorder characterized by a type IV delayed-type hypersensitivity reaction that occurs when a patient’s skin is exposed to a substance easily penetrates the skin barrier.
Increasingly recognized in the United States, many pediatric patients are becoming sensitized to contact allergens found in personal care products, including skin care products, topical medications, and clothing.
A study published by Hill et al. in 2016 reviewed pediatric patch test studies to determine the top contact allergens in children (Expert Rev Clin Immunol. 2016;12[5]:551-61).
Dr. Matiz presented the top 10 allergens discovered by this group, and offered practical advice for allergen avoidance.
Topping the list in descending order are the following:
- Tixocortol pivalate (a corticosteroid).
- Propylene glycol.
- Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI).
- Formaldehyde.
- Cocamidopropyl betaine.
- Lanolin.
- Benzalkonium chloride.
- Fragrance and balsam of peru.
- Neomycin.
- Nickel.
Dr. Matiz educated meeting attendees on allergen-containing products and clinical correlations suggestive of allergic sensitization to common allergens. Tixocortol pivilate is a corticosteroid present in Class A corticosteroids including hydrocortisone acetate. She highlighted the cross reactivity between class A and class D2 corticosteroids including hydrocortisone butyrate and valerate.
“Usually topical corticosteroid–contact sensitivity manifests as a failure to improve or worsening of existing dermatitis,” emphasized Dr. Matiz of departments of dermatology and pediatrics at the university.
Propylene glycol, benzalkonium chloride, and neomycin also represent top contact allergens frequently found in topical medications. Similarly, lanolin contact sensitivity often presents as refractory or worsening atopic dermatitis. “Lanolin, also known as wool alcohol, is commonly found in emollients, medications, and personal care products used by atopic dermatitis patients,” Dr. Matiz stressed.
Methylchloroisothiazolinone/methylisothiazolinone represent preservatives commonly found in wet wipes, hypoallergenic, and sensitive skin products. This was the allergen of the year in 2013 and was subsequently removed from many wet wipe formulations and products in response.
In addition to acute management of allergic contact dermatitis with corticosteroids, Dr. Matiz further emphasized the importance of preemptive avoidance of the top ten allergens.
She recommends patch testing if no clinical improvement is evident after 8 weeks of common allergen avoidance, for definitive allergen identification.
Dr. Matiz said she had no relevant financial disclosures.
Contact dermatitis should be suspected in patients with eczematous dermatitis atypical in location, geometric or symmetric in distribution, or unresponsive to or worsened by common therapies, Dr. Catalina Matiz emphasized.
Allergic contact dermatitis is a complex disorder characterized by a type IV delayed-type hypersensitivity reaction that occurs when a patient’s skin is exposed to a substance easily penetrates the skin barrier.
Increasingly recognized in the United States, many pediatric patients are becoming sensitized to contact allergens found in personal care products, including skin care products, topical medications, and clothing.
A study published by Hill et al. in 2016 reviewed pediatric patch test studies to determine the top contact allergens in children (Expert Rev Clin Immunol. 2016;12[5]:551-61).
Dr. Matiz presented the top 10 allergens discovered by this group, and offered practical advice for allergen avoidance.
Topping the list in descending order are the following:
- Tixocortol pivalate (a corticosteroid).
- Propylene glycol.
- Methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI).
- Formaldehyde.
- Cocamidopropyl betaine.
- Lanolin.
- Benzalkonium chloride.
- Fragrance and balsam of peru.
- Neomycin.
- Nickel.
Dr. Matiz educated meeting attendees on allergen-containing products and clinical correlations suggestive of allergic sensitization to common allergens. Tixocortol pivilate is a corticosteroid present in Class A corticosteroids including hydrocortisone acetate. She highlighted the cross reactivity between class A and class D2 corticosteroids including hydrocortisone butyrate and valerate.
“Usually topical corticosteroid–contact sensitivity manifests as a failure to improve or worsening of existing dermatitis,” emphasized Dr. Matiz of departments of dermatology and pediatrics at the university.
Propylene glycol, benzalkonium chloride, and neomycin also represent top contact allergens frequently found in topical medications. Similarly, lanolin contact sensitivity often presents as refractory or worsening atopic dermatitis. “Lanolin, also known as wool alcohol, is commonly found in emollients, medications, and personal care products used by atopic dermatitis patients,” Dr. Matiz stressed.
Methylchloroisothiazolinone/methylisothiazolinone represent preservatives commonly found in wet wipes, hypoallergenic, and sensitive skin products. This was the allergen of the year in 2013 and was subsequently removed from many wet wipe formulations and products in response.
In addition to acute management of allergic contact dermatitis with corticosteroids, Dr. Matiz further emphasized the importance of preemptive avoidance of the top ten allergens.
She recommends patch testing if no clinical improvement is evident after 8 weeks of common allergen avoidance, for definitive allergen identification.
Dr. Matiz said she had no relevant financial disclosures.
High-dose oral vitamin D3 significantly reduced effects of sunburn
PORTLAND, ORE. – When given within an hour, a single dose of at least 100,000 IU vitamin D3 rapidly attenuates sunburn, according to the results of a randomized, double-blind, placebo-controlled pilot study of 25 healthy adults.
This is the first in vivo study to evaluate whether vitamin D3 can modulate acute inflammation in target tissues, Jeffrey F. Scott, MD, wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology. The findings “have broad implications for the role of vitamin D in skin homeostasis, and suggest that oral vitamin D may be clinically therapeutic for its immunomodulatory properties,” he and his coauthors concluded.
Higher doses of vitamin D3 also produced significant decreases in skin levels of tumor necrosis factor–alpha (TNF-alpha) (P = .02) and inducible nitric oxide synthase (iNOS) (P = .04) compared with placebo, reported Dr. Scott, a resident in dermatology at University Hospitals Cleveland Medical Center.
Notably, 48 hours after sunburn, hematoxylin and eosin histology of punch biopsies showed that participants who received 200,000 IU vitamin D3 had the least structural damage to the skin, while placebo recipients had the most damage. Expression profiling also linked vitamin D3 treatment with upregulation of genes associated with skin barrier repair.
Studies continue to document diverse biologic effects of vitamin D, including “modulation of immune response, inflammatory disease, cardiovascular health, and carcinogenesis,” the researchers wrote. Vitamin D3 also has been shown to suppress inflammatory mediators and induce autophagy, they added. Previously, their group showed that oral D3 induced similar protective effects in a mouse model of chemical skin injury. Treatment inhibited proinflammatory cytokines and chemokines within the skin, including iNOS and TNF-alpha.
The current study also included a control phase in which participants underwent experimental sunburn on the right arm without any treatment. Forty-eight hours later, punch biopsies revealed high levels of iNOS and TNF-alpha, with increased expression of proinflammatory genes, the researchers wrote.
During the subsequent experimental phase, seven participants were assigned to receive placebo, and six were assigned to receive 50,000 IU, 100,000 IU, or 200,000 IU of vitamin D3. After treatment, participants with the highest serum D3 levels had significantly decreased skin redness compared with participants with lower serum D3 levels (P less than .05). Higher vitamin D3 serum levels were also associated with significant (P less than .05) upregulation of skin barrier repair genes and of arginase-1, a cytosolic enzyme that helps mediate anti-inflammatory activity.
“Arginase-1 may be a clinically useful tissue biomarker for monitoring the immunomodulatory effects of vitamin D3 in humans,” the researchers concluded.
The National Institute of Arthritis Musculoskeletal and Skin Diseases and the National Institutes of Health supported the work. Dr. Scott had no relevant financial disclosures.
PORTLAND, ORE. – When given within an hour, a single dose of at least 100,000 IU vitamin D3 rapidly attenuates sunburn, according to the results of a randomized, double-blind, placebo-controlled pilot study of 25 healthy adults.
This is the first in vivo study to evaluate whether vitamin D3 can modulate acute inflammation in target tissues, Jeffrey F. Scott, MD, wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology. The findings “have broad implications for the role of vitamin D in skin homeostasis, and suggest that oral vitamin D may be clinically therapeutic for its immunomodulatory properties,” he and his coauthors concluded.
Higher doses of vitamin D3 also produced significant decreases in skin levels of tumor necrosis factor–alpha (TNF-alpha) (P = .02) and inducible nitric oxide synthase (iNOS) (P = .04) compared with placebo, reported Dr. Scott, a resident in dermatology at University Hospitals Cleveland Medical Center.
Notably, 48 hours after sunburn, hematoxylin and eosin histology of punch biopsies showed that participants who received 200,000 IU vitamin D3 had the least structural damage to the skin, while placebo recipients had the most damage. Expression profiling also linked vitamin D3 treatment with upregulation of genes associated with skin barrier repair.
Studies continue to document diverse biologic effects of vitamin D, including “modulation of immune response, inflammatory disease, cardiovascular health, and carcinogenesis,” the researchers wrote. Vitamin D3 also has been shown to suppress inflammatory mediators and induce autophagy, they added. Previously, their group showed that oral D3 induced similar protective effects in a mouse model of chemical skin injury. Treatment inhibited proinflammatory cytokines and chemokines within the skin, including iNOS and TNF-alpha.
The current study also included a control phase in which participants underwent experimental sunburn on the right arm without any treatment. Forty-eight hours later, punch biopsies revealed high levels of iNOS and TNF-alpha, with increased expression of proinflammatory genes, the researchers wrote.
During the subsequent experimental phase, seven participants were assigned to receive placebo, and six were assigned to receive 50,000 IU, 100,000 IU, or 200,000 IU of vitamin D3. After treatment, participants with the highest serum D3 levels had significantly decreased skin redness compared with participants with lower serum D3 levels (P less than .05). Higher vitamin D3 serum levels were also associated with significant (P less than .05) upregulation of skin barrier repair genes and of arginase-1, a cytosolic enzyme that helps mediate anti-inflammatory activity.
“Arginase-1 may be a clinically useful tissue biomarker for monitoring the immunomodulatory effects of vitamin D3 in humans,” the researchers concluded.
The National Institute of Arthritis Musculoskeletal and Skin Diseases and the National Institutes of Health supported the work. Dr. Scott had no relevant financial disclosures.
PORTLAND, ORE. – When given within an hour, a single dose of at least 100,000 IU vitamin D3 rapidly attenuates sunburn, according to the results of a randomized, double-blind, placebo-controlled pilot study of 25 healthy adults.
This is the first in vivo study to evaluate whether vitamin D3 can modulate acute inflammation in target tissues, Jeffrey F. Scott, MD, wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology. The findings “have broad implications for the role of vitamin D in skin homeostasis, and suggest that oral vitamin D may be clinically therapeutic for its immunomodulatory properties,” he and his coauthors concluded.
Higher doses of vitamin D3 also produced significant decreases in skin levels of tumor necrosis factor–alpha (TNF-alpha) (P = .02) and inducible nitric oxide synthase (iNOS) (P = .04) compared with placebo, reported Dr. Scott, a resident in dermatology at University Hospitals Cleveland Medical Center.
Notably, 48 hours after sunburn, hematoxylin and eosin histology of punch biopsies showed that participants who received 200,000 IU vitamin D3 had the least structural damage to the skin, while placebo recipients had the most damage. Expression profiling also linked vitamin D3 treatment with upregulation of genes associated with skin barrier repair.
Studies continue to document diverse biologic effects of vitamin D, including “modulation of immune response, inflammatory disease, cardiovascular health, and carcinogenesis,” the researchers wrote. Vitamin D3 also has been shown to suppress inflammatory mediators and induce autophagy, they added. Previously, their group showed that oral D3 induced similar protective effects in a mouse model of chemical skin injury. Treatment inhibited proinflammatory cytokines and chemokines within the skin, including iNOS and TNF-alpha.
The current study also included a control phase in which participants underwent experimental sunburn on the right arm without any treatment. Forty-eight hours later, punch biopsies revealed high levels of iNOS and TNF-alpha, with increased expression of proinflammatory genes, the researchers wrote.
During the subsequent experimental phase, seven participants were assigned to receive placebo, and six were assigned to receive 50,000 IU, 100,000 IU, or 200,000 IU of vitamin D3. After treatment, participants with the highest serum D3 levels had significantly decreased skin redness compared with participants with lower serum D3 levels (P less than .05). Higher vitamin D3 serum levels were also associated with significant (P less than .05) upregulation of skin barrier repair genes and of arginase-1, a cytosolic enzyme that helps mediate anti-inflammatory activity.
“Arginase-1 may be a clinically useful tissue biomarker for monitoring the immunomodulatory effects of vitamin D3 in humans,” the researchers concluded.
The National Institute of Arthritis Musculoskeletal and Skin Diseases and the National Institutes of Health supported the work. Dr. Scott had no relevant financial disclosures.
Key clinical point: A single dose of at least 100,000 IU vitamin D3 rapidly attenuated experimental sunburn.
Major finding: Twenty-four hours after sunburn, recipients of 100,000 IU or 200,000 IU D3 had a marked, sustained reduction in skin redness compared with the placebo and 50,000 IU groups. Higher doses of D3 produced significant decreases in skin levels of tumor necrosis factor–alpha and inducible nitric oxide synthase, compared with placebo.
Data source: A double-blind, randomized, placebo-controlled pilot study of 25 healthy adults.
Disclosures: The National Institute of Arthritis Musculoskeletal and Skin Diseases and the National Institutes of Health supported the work. Dr. Scott had no relevant financial conflicts.
U.S. Zika epidemic could cost billions, or less
A Zika virus epidemic could cost the United States $183 million … or $680 million … or $2.2 billion, according to a new computational model developed to estimate Zika’s economic impact.
The model’s seeming lack of conviction comes from its options for an attack rate – the percentage of the population infected by the virus. An epidemic with a low attack rate of 0.01% would be expected to result in over 7,000 symptomatic cases and cost $183 million in direct medical costs and losses in productivity, said Bruce Y. Lee, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates (PLoS Negl Trop Dis. 2017 Apr 27;11[4]:e0005531).
The investigators based their model on the six states at the highest risk for local Zika emergence: Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas. The hypothetical epidemic lasts 230 days, which is equivalent to the Zika-related microcephaly outbreak in Brazil in 2015.
The National Institutes of Health, the Agency for Healthcare Research and Quality, and the United States Agency for International Development funded the study. The authors declared that no competing interests exist.
A Zika virus epidemic could cost the United States $183 million … or $680 million … or $2.2 billion, according to a new computational model developed to estimate Zika’s economic impact.
The model’s seeming lack of conviction comes from its options for an attack rate – the percentage of the population infected by the virus. An epidemic with a low attack rate of 0.01% would be expected to result in over 7,000 symptomatic cases and cost $183 million in direct medical costs and losses in productivity, said Bruce Y. Lee, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates (PLoS Negl Trop Dis. 2017 Apr 27;11[4]:e0005531).
The investigators based their model on the six states at the highest risk for local Zika emergence: Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas. The hypothetical epidemic lasts 230 days, which is equivalent to the Zika-related microcephaly outbreak in Brazil in 2015.
The National Institutes of Health, the Agency for Healthcare Research and Quality, and the United States Agency for International Development funded the study. The authors declared that no competing interests exist.
A Zika virus epidemic could cost the United States $183 million … or $680 million … or $2.2 billion, according to a new computational model developed to estimate Zika’s economic impact.
The model’s seeming lack of conviction comes from its options for an attack rate – the percentage of the population infected by the virus. An epidemic with a low attack rate of 0.01% would be expected to result in over 7,000 symptomatic cases and cost $183 million in direct medical costs and losses in productivity, said Bruce Y. Lee, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates (PLoS Negl Trop Dis. 2017 Apr 27;11[4]:e0005531).
The investigators based their model on the six states at the highest risk for local Zika emergence: Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas. The hypothetical epidemic lasts 230 days, which is equivalent to the Zika-related microcephaly outbreak in Brazil in 2015.
The National Institutes of Health, the Agency for Healthcare Research and Quality, and the United States Agency for International Development funded the study. The authors declared that no competing interests exist.
FROM PLOS NEGLECTED TROPICAL DISEASES
A note about OpenNotes
“He is a frequent flyer.” This is a term we reserve for patients who consume a lot of services. In the outpatient clinic, it’s the type of patient who comes for frequent visits, perhaps more often than medically necessary. Oftentimes, more than we’d like. They can be demanding. They can also be an invaluable resource: None of your patients will likely be more forthright with you than those who are so motivated.
I saw one of my frequent flyer patients recently. He, like all patients, has medical problems, but, unlike most, he never misses an opportunity to schedule an appointment to solve them. A once red-, now gray-haired engineer, he has quite a record of skin issues and has meticulously documented all of them himself.
I felt myself stiffening. I added him on to my schedule today because I’m a good guy, yet he wants a piece of me? Bring it.
“So, you can read my notes online?” I asked. “Yes,” he replied, “for some reason I can read all of my charts for dermatology visits.”
“Well, that’s because I volunteered for our OpenNotes program,” I said. As a participant, all of my patients are able to read all of my notes, if they choose to do so. They can access them but cannot make any changes.
Yeah, great idea, Jeff.
“I just want to know, why would you put that if you didn’t do it?” he asked.
“Well, it’s not a lie. We did discuss the risks and benefits of my freezing your AKs previously, right?” “Yes, we did,” he replied. “Did you not want me to freeze them?” I asked. “No, I did,” he answered. “I just wanted you to know that I can see what you write about me, and I don’t want you to say anything you don’t want me to read because I really trust you.”
“I won’t,” I said.
That’s because I understand that you are my patient, and all patients deserve my unmitigated care. It’s what makes me a doctor.
I’ve since added to my EMR template: “Previously discussed risks and benefits.” Not because it really matters. But because it matters to him. And that matters to me.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @dermdoc on Twitter. Write to him at [email protected].
“He is a frequent flyer.” This is a term we reserve for patients who consume a lot of services. In the outpatient clinic, it’s the type of patient who comes for frequent visits, perhaps more often than medically necessary. Oftentimes, more than we’d like. They can be demanding. They can also be an invaluable resource: None of your patients will likely be more forthright with you than those who are so motivated.
I saw one of my frequent flyer patients recently. He, like all patients, has medical problems, but, unlike most, he never misses an opportunity to schedule an appointment to solve them. A once red-, now gray-haired engineer, he has quite a record of skin issues and has meticulously documented all of them himself.
I felt myself stiffening. I added him on to my schedule today because I’m a good guy, yet he wants a piece of me? Bring it.
“So, you can read my notes online?” I asked. “Yes,” he replied, “for some reason I can read all of my charts for dermatology visits.”
“Well, that’s because I volunteered for our OpenNotes program,” I said. As a participant, all of my patients are able to read all of my notes, if they choose to do so. They can access them but cannot make any changes.
Yeah, great idea, Jeff.
“I just want to know, why would you put that if you didn’t do it?” he asked.
“Well, it’s not a lie. We did discuss the risks and benefits of my freezing your AKs previously, right?” “Yes, we did,” he replied. “Did you not want me to freeze them?” I asked. “No, I did,” he answered. “I just wanted you to know that I can see what you write about me, and I don’t want you to say anything you don’t want me to read because I really trust you.”
“I won’t,” I said.
That’s because I understand that you are my patient, and all patients deserve my unmitigated care. It’s what makes me a doctor.
I’ve since added to my EMR template: “Previously discussed risks and benefits.” Not because it really matters. But because it matters to him. And that matters to me.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @dermdoc on Twitter. Write to him at [email protected].
“He is a frequent flyer.” This is a term we reserve for patients who consume a lot of services. In the outpatient clinic, it’s the type of patient who comes for frequent visits, perhaps more often than medically necessary. Oftentimes, more than we’d like. They can be demanding. They can also be an invaluable resource: None of your patients will likely be more forthright with you than those who are so motivated.
I saw one of my frequent flyer patients recently. He, like all patients, has medical problems, but, unlike most, he never misses an opportunity to schedule an appointment to solve them. A once red-, now gray-haired engineer, he has quite a record of skin issues and has meticulously documented all of them himself.
I felt myself stiffening. I added him on to my schedule today because I’m a good guy, yet he wants a piece of me? Bring it.
“So, you can read my notes online?” I asked. “Yes,” he replied, “for some reason I can read all of my charts for dermatology visits.”
“Well, that’s because I volunteered for our OpenNotes program,” I said. As a participant, all of my patients are able to read all of my notes, if they choose to do so. They can access them but cannot make any changes.
Yeah, great idea, Jeff.
“I just want to know, why would you put that if you didn’t do it?” he asked.
“Well, it’s not a lie. We did discuss the risks and benefits of my freezing your AKs previously, right?” “Yes, we did,” he replied. “Did you not want me to freeze them?” I asked. “No, I did,” he answered. “I just wanted you to know that I can see what you write about me, and I don’t want you to say anything you don’t want me to read because I really trust you.”
“I won’t,” I said.
That’s because I understand that you are my patient, and all patients deserve my unmitigated care. It’s what makes me a doctor.
I’ve since added to my EMR template: “Previously discussed risks and benefits.” Not because it really matters. But because it matters to him. And that matters to me.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @dermdoc on Twitter. Write to him at [email protected].
For vertebral osteomyelitis, early switch to oral antibiotics is feasible
VIENNA – A 6-week course of antibiotics, with an early switch from intravenous to oral, appears to be a safe and appropriate option for some patients with pyogenic vertebral osteomyelitis.
A single-center retrospective study of 82 such patients found two treatment failures and two deaths over 1 year (4.8% failure rate). The patients who died were very elderly with serious comorbidities. The two treatment failures occurred in patients with methicillin-resistant coagulase-negative staphylococcal infections of a central catheter.
“Only two of the failures were due to inadequate antibiotic treatment,” Adrien Lemaignen, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. “Both patients experienced a relapse of bacteremia with the same bacteria a few days after antibiotic cessation in a context of conservative treatment of a catheter-related infection.”
Guidelines recently adopted by the Infectious Diseases Society of America inspired the study, said Dr. Lemaignen of University Hospital of Tours, France. The 2015 document calls for 6-8 weeks of antibiotics, depending upon the infective organism and whether infective endocarditis complicates management. All suggested antibiotic regimens call for initial IV therapy followed by oral, but there are no cut-and-dried recommendations about when to switch. The guideline notes one study in which patients switched to oral after about 2.7 weeks, with a 97% success rate.
Dr. Lemaignen and his colleagues set out to determine cure rates of early oral relay in 82 patients with pyogenic vertebral osteomyelitis (PVO). All patients were treated at a single center from 2011 to 2016. The team defined treatment failure as death, or persistence or relapse of infection in the first year after treatment.
All patients had culture-proven PVO that also was visible on imaging. Patients were excluded if they had any brucellar, fungal, or mycobacterial coinfections, or if they had infected spinal implants.
The mean age of the patients in the cohort was 66 years; 39% had some neuropathology. The mean C-reactive protein level was 115 mg/L. More than half of the cases (56%) involved the lumbar-sacral spine; 30% were thoracic, and the remainder, cervical. About one-fifth had multiple level involvement. There was epidural inflammation in 68%, epidural abscess in 13%, and extradural abscess in 26%.
Staphylococcus aureus was the most common pathogen (34%); two infections were methicillin resistant. Other infective organisms were streptococci (27%), Gram-negative bacilli (15%), and coagulase-negative staph (12%). A few patients had enterococci (5%) or polymicrobial infections (7%).
Infective endocarditis was present in 16 patients; this was associated with enterococcal and streptococcal infections.
Treatment varied by pathogen. Patients with S. aureus received penicillin or cefazolin with an oral relay to fluoroquinolone/rifampicin or clindamycin. Those with streptococci received amoxicillin with or without an aminoglycoside, followed by oral amoxicillin or clindamycin. Those with coagulase-negative streptococci received a glycopeptide with or without blasticidin, followed by fluoroquinolone/rifampicin. Patients with enterococcal infections got a third generation cephalosporin followed by an oral third generation cephalosporin or a fluoroquinolone.
All but six patients received 6 weeks of treatment.
The mean oral relay occurred on day 12, but 30 patients (36%) were able to switch before 7 days elapsed. Thirteen patients had to stay on the IV route for their entire treatment; 25% of this group had infective endocarditis. Six patients, all of whom had motor symptoms, also needed surgery.
The median follow-up was 358 days. During this time, there were two deaths and two treatment failures.
One death was a 93-year-old who had a controlled sepsis, but died at day 79 of a massive hematemesis. The other was an 80-year-old with an amoxicillin-resistant staph infection and decompensated cirrhosis who died at day 49.
There were also two treatment failures. Both of these patients had methicillin-resistant coagulase-negative staph infections of indwelling central catheters. One had a relapse 70 days after the end of IV therapy; the other relapsed on day 26 of treatment, after a 2-week course of oral antibiotics.
Not all patients were able to succeed with 6 weeks of therapy. Three needed prolonged treatment: One of these had an infected vascular prosthesis and two were immunocompromised patients who had cervical osteomyelitis with multiple abscesses.
In light of these results, Dr. Lemaignen said, “We can say confirm the safety of short IV treatment with an early oral relay in pyogenic vertebral osteomyelitis under real-life conditions, with 95% success rate and good functional outcomes at 6 months.”
He had no relevant financial disclosures.
[email protected]
On Twitter @Alz_gal
VIENNA – A 6-week course of antibiotics, with an early switch from intravenous to oral, appears to be a safe and appropriate option for some patients with pyogenic vertebral osteomyelitis.
A single-center retrospective study of 82 such patients found two treatment failures and two deaths over 1 year (4.8% failure rate). The patients who died were very elderly with serious comorbidities. The two treatment failures occurred in patients with methicillin-resistant coagulase-negative staphylococcal infections of a central catheter.
“Only two of the failures were due to inadequate antibiotic treatment,” Adrien Lemaignen, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. “Both patients experienced a relapse of bacteremia with the same bacteria a few days after antibiotic cessation in a context of conservative treatment of a catheter-related infection.”
Guidelines recently adopted by the Infectious Diseases Society of America inspired the study, said Dr. Lemaignen of University Hospital of Tours, France. The 2015 document calls for 6-8 weeks of antibiotics, depending upon the infective organism and whether infective endocarditis complicates management. All suggested antibiotic regimens call for initial IV therapy followed by oral, but there are no cut-and-dried recommendations about when to switch. The guideline notes one study in which patients switched to oral after about 2.7 weeks, with a 97% success rate.
Dr. Lemaignen and his colleagues set out to determine cure rates of early oral relay in 82 patients with pyogenic vertebral osteomyelitis (PVO). All patients were treated at a single center from 2011 to 2016. The team defined treatment failure as death, or persistence or relapse of infection in the first year after treatment.
All patients had culture-proven PVO that also was visible on imaging. Patients were excluded if they had any brucellar, fungal, or mycobacterial coinfections, or if they had infected spinal implants.
The mean age of the patients in the cohort was 66 years; 39% had some neuropathology. The mean C-reactive protein level was 115 mg/L. More than half of the cases (56%) involved the lumbar-sacral spine; 30% were thoracic, and the remainder, cervical. About one-fifth had multiple level involvement. There was epidural inflammation in 68%, epidural abscess in 13%, and extradural abscess in 26%.
Staphylococcus aureus was the most common pathogen (34%); two infections were methicillin resistant. Other infective organisms were streptococci (27%), Gram-negative bacilli (15%), and coagulase-negative staph (12%). A few patients had enterococci (5%) or polymicrobial infections (7%).
Infective endocarditis was present in 16 patients; this was associated with enterococcal and streptococcal infections.
Treatment varied by pathogen. Patients with S. aureus received penicillin or cefazolin with an oral relay to fluoroquinolone/rifampicin or clindamycin. Those with streptococci received amoxicillin with or without an aminoglycoside, followed by oral amoxicillin or clindamycin. Those with coagulase-negative streptococci received a glycopeptide with or without blasticidin, followed by fluoroquinolone/rifampicin. Patients with enterococcal infections got a third generation cephalosporin followed by an oral third generation cephalosporin or a fluoroquinolone.
All but six patients received 6 weeks of treatment.
The mean oral relay occurred on day 12, but 30 patients (36%) were able to switch before 7 days elapsed. Thirteen patients had to stay on the IV route for their entire treatment; 25% of this group had infective endocarditis. Six patients, all of whom had motor symptoms, also needed surgery.
The median follow-up was 358 days. During this time, there were two deaths and two treatment failures.
One death was a 93-year-old who had a controlled sepsis, but died at day 79 of a massive hematemesis. The other was an 80-year-old with an amoxicillin-resistant staph infection and decompensated cirrhosis who died at day 49.
There were also two treatment failures. Both of these patients had methicillin-resistant coagulase-negative staph infections of indwelling central catheters. One had a relapse 70 days after the end of IV therapy; the other relapsed on day 26 of treatment, after a 2-week course of oral antibiotics.
Not all patients were able to succeed with 6 weeks of therapy. Three needed prolonged treatment: One of these had an infected vascular prosthesis and two were immunocompromised patients who had cervical osteomyelitis with multiple abscesses.
In light of these results, Dr. Lemaignen said, “We can say confirm the safety of short IV treatment with an early oral relay in pyogenic vertebral osteomyelitis under real-life conditions, with 95% success rate and good functional outcomes at 6 months.”
He had no relevant financial disclosures.
[email protected]
On Twitter @Alz_gal
VIENNA – A 6-week course of antibiotics, with an early switch from intravenous to oral, appears to be a safe and appropriate option for some patients with pyogenic vertebral osteomyelitis.
A single-center retrospective study of 82 such patients found two treatment failures and two deaths over 1 year (4.8% failure rate). The patients who died were very elderly with serious comorbidities. The two treatment failures occurred in patients with methicillin-resistant coagulase-negative staphylococcal infections of a central catheter.
“Only two of the failures were due to inadequate antibiotic treatment,” Adrien Lemaignen, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. “Both patients experienced a relapse of bacteremia with the same bacteria a few days after antibiotic cessation in a context of conservative treatment of a catheter-related infection.”
Guidelines recently adopted by the Infectious Diseases Society of America inspired the study, said Dr. Lemaignen of University Hospital of Tours, France. The 2015 document calls for 6-8 weeks of antibiotics, depending upon the infective organism and whether infective endocarditis complicates management. All suggested antibiotic regimens call for initial IV therapy followed by oral, but there are no cut-and-dried recommendations about when to switch. The guideline notes one study in which patients switched to oral after about 2.7 weeks, with a 97% success rate.
Dr. Lemaignen and his colleagues set out to determine cure rates of early oral relay in 82 patients with pyogenic vertebral osteomyelitis (PVO). All patients were treated at a single center from 2011 to 2016. The team defined treatment failure as death, or persistence or relapse of infection in the first year after treatment.
All patients had culture-proven PVO that also was visible on imaging. Patients were excluded if they had any brucellar, fungal, or mycobacterial coinfections, or if they had infected spinal implants.
The mean age of the patients in the cohort was 66 years; 39% had some neuropathology. The mean C-reactive protein level was 115 mg/L. More than half of the cases (56%) involved the lumbar-sacral spine; 30% were thoracic, and the remainder, cervical. About one-fifth had multiple level involvement. There was epidural inflammation in 68%, epidural abscess in 13%, and extradural abscess in 26%.
Staphylococcus aureus was the most common pathogen (34%); two infections were methicillin resistant. Other infective organisms were streptococci (27%), Gram-negative bacilli (15%), and coagulase-negative staph (12%). A few patients had enterococci (5%) or polymicrobial infections (7%).
Infective endocarditis was present in 16 patients; this was associated with enterococcal and streptococcal infections.
Treatment varied by pathogen. Patients with S. aureus received penicillin or cefazolin with an oral relay to fluoroquinolone/rifampicin or clindamycin. Those with streptococci received amoxicillin with or without an aminoglycoside, followed by oral amoxicillin or clindamycin. Those with coagulase-negative streptococci received a glycopeptide with or without blasticidin, followed by fluoroquinolone/rifampicin. Patients with enterococcal infections got a third generation cephalosporin followed by an oral third generation cephalosporin or a fluoroquinolone.
All but six patients received 6 weeks of treatment.
The mean oral relay occurred on day 12, but 30 patients (36%) were able to switch before 7 days elapsed. Thirteen patients had to stay on the IV route for their entire treatment; 25% of this group had infective endocarditis. Six patients, all of whom had motor symptoms, also needed surgery.
The median follow-up was 358 days. During this time, there were two deaths and two treatment failures.
One death was a 93-year-old who had a controlled sepsis, but died at day 79 of a massive hematemesis. The other was an 80-year-old with an amoxicillin-resistant staph infection and decompensated cirrhosis who died at day 49.
There were also two treatment failures. Both of these patients had methicillin-resistant coagulase-negative staph infections of indwelling central catheters. One had a relapse 70 days after the end of IV therapy; the other relapsed on day 26 of treatment, after a 2-week course of oral antibiotics.
Not all patients were able to succeed with 6 weeks of therapy. Three needed prolonged treatment: One of these had an infected vascular prosthesis and two were immunocompromised patients who had cervical osteomyelitis with multiple abscesses.
In light of these results, Dr. Lemaignen said, “We can say confirm the safety of short IV treatment with an early oral relay in pyogenic vertebral osteomyelitis under real-life conditions, with 95% success rate and good functional outcomes at 6 months.”
He had no relevant financial disclosures.
[email protected]
On Twitter @Alz_gal
AT ECCMID 2017
Key clinical point:
Major finding: There were two treatment failures attributable to the antibiotic regimen, and two deaths that were not, for a total treatment success rate of 95%.
Data source: A retrospective cohort comprising 82 patients.
Disclosures: Dr. Lemaignen had no financial disclosures.
Ribaxamase prevented C. difficile infections by protecting microbiome
VIENNA – An investigational beta-lactamase reduced Clostridium difficile infections by 71% in patients receiving extended antibiotic therapy for respiratory infections but not by killing the opportunistic bacteria.
Rather, ribaxamase prevented C. difficile infections (CDI) by breaking down excess therapeutic antibiotics in the gut before they could injure an otherwise healthy microbiome, John Kokai-Kun, PhD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Ribaxamase is an oral enzyme that breaks the lactam ring in penicillins and cephalosporins. It’s formulated to release at a pH of 5.5 or higher, an environment that begins to develop in the upper small intestine near the bile duct – the same place that excess antibiotics are excreted.
“The drug is intended to be administered during, and for a short time after, intravenous administration of specific beta-lactam–containing antibiotics,” Dr. Kokai-Kun said. Ribaxamase doesn’t work on carbapenem-type antibiotics, he noted, and Synthetic Biologics is working on an effective enzyme for those as well.
In early human studies, ribaxamase was well tolerated and didn’t interfere with the pharmacokinetics of therapeutic antibiotics (Antimicrob Agents Chemother. 2017 Mar;61[3]:e02197-16). It’s also effective in patients who are taking a proton pump inhibitor, he said.
Dr. Kokai-Kun reported the results of a phase IIb study of 412 patients who received IV ceftriaxone for lower respiratory infections. They were assigned 1:1 to either 150 mg ribaxamase daily or placebo throughout the IV treatment and for 3 days after.
The primary endpoint was prevention of C. difficile infection. The secondary endpoint was prevention of non–C. difficile antibiotic-associated diarrhea. An exploratory endpoint examined the drug’s ability to protect the microbiome. Patients were monitored for 6 weeks after treatment stopped.
The cohort was a mean 70 years old. One-third of patients also received a macrolide during their hospitalization, and one-third were taking proton pump inhibitors. The respiratory infection cure rate was about 99% in both groups at both 72 hours and 4 weeks.
Eight patients in the placebo group (3.8%) and two in the active group (less than 1%) developed C. difficile infection. That translated to a statistically significant 71% risk reduction, with a P value of .027, Dr. Kokai-Kun said. Ribaxamase did not hit its secondary endpoint of preventing all-cause diarrhea or antibiotic-associated diarrhea that was not caused by C. difficile infection.
Although not a primary finding, ribaxamase also inhibited colonization by vancomycin-resistant enterococci, which occurred in about 70 (40%) patients in the placebo group and 40 (20%) in the ribaxamase group at both 72 hours and 4 weeks.
All patients contributed stool samples at baseline and after treatment for microbiome analysis. That portion of the study is still ongoing, Dr. Kokai-Kun said.
Synthetic Biologics sponsored the study and is developing ribaxamase. Dr. Kokai-Kun is the company’s vice president of nonclinical affairs.
[email protected]
On Twitter @alz_gal
VIENNA – An investigational beta-lactamase reduced Clostridium difficile infections by 71% in patients receiving extended antibiotic therapy for respiratory infections but not by killing the opportunistic bacteria.
Rather, ribaxamase prevented C. difficile infections (CDI) by breaking down excess therapeutic antibiotics in the gut before they could injure an otherwise healthy microbiome, John Kokai-Kun, PhD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Ribaxamase is an oral enzyme that breaks the lactam ring in penicillins and cephalosporins. It’s formulated to release at a pH of 5.5 or higher, an environment that begins to develop in the upper small intestine near the bile duct – the same place that excess antibiotics are excreted.
“The drug is intended to be administered during, and for a short time after, intravenous administration of specific beta-lactam–containing antibiotics,” Dr. Kokai-Kun said. Ribaxamase doesn’t work on carbapenem-type antibiotics, he noted, and Synthetic Biologics is working on an effective enzyme for those as well.
In early human studies, ribaxamase was well tolerated and didn’t interfere with the pharmacokinetics of therapeutic antibiotics (Antimicrob Agents Chemother. 2017 Mar;61[3]:e02197-16). It’s also effective in patients who are taking a proton pump inhibitor, he said.
Dr. Kokai-Kun reported the results of a phase IIb study of 412 patients who received IV ceftriaxone for lower respiratory infections. They were assigned 1:1 to either 150 mg ribaxamase daily or placebo throughout the IV treatment and for 3 days after.
The primary endpoint was prevention of C. difficile infection. The secondary endpoint was prevention of non–C. difficile antibiotic-associated diarrhea. An exploratory endpoint examined the drug’s ability to protect the microbiome. Patients were monitored for 6 weeks after treatment stopped.
The cohort was a mean 70 years old. One-third of patients also received a macrolide during their hospitalization, and one-third were taking proton pump inhibitors. The respiratory infection cure rate was about 99% in both groups at both 72 hours and 4 weeks.
Eight patients in the placebo group (3.8%) and two in the active group (less than 1%) developed C. difficile infection. That translated to a statistically significant 71% risk reduction, with a P value of .027, Dr. Kokai-Kun said. Ribaxamase did not hit its secondary endpoint of preventing all-cause diarrhea or antibiotic-associated diarrhea that was not caused by C. difficile infection.
Although not a primary finding, ribaxamase also inhibited colonization by vancomycin-resistant enterococci, which occurred in about 70 (40%) patients in the placebo group and 40 (20%) in the ribaxamase group at both 72 hours and 4 weeks.
All patients contributed stool samples at baseline and after treatment for microbiome analysis. That portion of the study is still ongoing, Dr. Kokai-Kun said.
Synthetic Biologics sponsored the study and is developing ribaxamase. Dr. Kokai-Kun is the company’s vice president of nonclinical affairs.
[email protected]
On Twitter @alz_gal
VIENNA – An investigational beta-lactamase reduced Clostridium difficile infections by 71% in patients receiving extended antibiotic therapy for respiratory infections but not by killing the opportunistic bacteria.
Rather, ribaxamase prevented C. difficile infections (CDI) by breaking down excess therapeutic antibiotics in the gut before they could injure an otherwise healthy microbiome, John Kokai-Kun, PhD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Ribaxamase is an oral enzyme that breaks the lactam ring in penicillins and cephalosporins. It’s formulated to release at a pH of 5.5 or higher, an environment that begins to develop in the upper small intestine near the bile duct – the same place that excess antibiotics are excreted.
“The drug is intended to be administered during, and for a short time after, intravenous administration of specific beta-lactam–containing antibiotics,” Dr. Kokai-Kun said. Ribaxamase doesn’t work on carbapenem-type antibiotics, he noted, and Synthetic Biologics is working on an effective enzyme for those as well.
In early human studies, ribaxamase was well tolerated and didn’t interfere with the pharmacokinetics of therapeutic antibiotics (Antimicrob Agents Chemother. 2017 Mar;61[3]:e02197-16). It’s also effective in patients who are taking a proton pump inhibitor, he said.
Dr. Kokai-Kun reported the results of a phase IIb study of 412 patients who received IV ceftriaxone for lower respiratory infections. They were assigned 1:1 to either 150 mg ribaxamase daily or placebo throughout the IV treatment and for 3 days after.
The primary endpoint was prevention of C. difficile infection. The secondary endpoint was prevention of non–C. difficile antibiotic-associated diarrhea. An exploratory endpoint examined the drug’s ability to protect the microbiome. Patients were monitored for 6 weeks after treatment stopped.
The cohort was a mean 70 years old. One-third of patients also received a macrolide during their hospitalization, and one-third were taking proton pump inhibitors. The respiratory infection cure rate was about 99% in both groups at both 72 hours and 4 weeks.
Eight patients in the placebo group (3.8%) and two in the active group (less than 1%) developed C. difficile infection. That translated to a statistically significant 71% risk reduction, with a P value of .027, Dr. Kokai-Kun said. Ribaxamase did not hit its secondary endpoint of preventing all-cause diarrhea or antibiotic-associated diarrhea that was not caused by C. difficile infection.
Although not a primary finding, ribaxamase also inhibited colonization by vancomycin-resistant enterococci, which occurred in about 70 (40%) patients in the placebo group and 40 (20%) in the ribaxamase group at both 72 hours and 4 weeks.
All patients contributed stool samples at baseline and after treatment for microbiome analysis. That portion of the study is still ongoing, Dr. Kokai-Kun said.
Synthetic Biologics sponsored the study and is developing ribaxamase. Dr. Kokai-Kun is the company’s vice president of nonclinical affairs.
[email protected]
On Twitter @alz_gal
AT ECCMID 2017
Key clinical point:
Major finding: Ribaxamase reduced C. difficile infections by 71%, relative to a placebo.
Data source: The study randomized 412 patients to either placebo or ribaxamase in addition to their therapeutic antibiotics.
Disclosures: Synthetic Biologics sponsored the study and is developing ribaxamase. Dr. Kokai-Kun is the company’s vice president of nonclinical affairs.