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Adjuvant chemotherapy overused in young patients with colon cancer
Adjuvant chemotherapy may be overused among younger patients with colon cancer, without clear evidence of survival benefit over surgery alone, according to a report in JAMA Surgery.
Using data from 3,143 patients with histologically confirmed primary colon adenocarcinoma in the U.S. Department of Defense’s Central Cancer Registry and Military Heath System medical claims databases, researchers compared overall survival in those who underwent surgery and adjuvant chemotherapy to those who underwent surgery alone.
They found patients aged 18-49 years were up to eight times more likely to receive postoperative systemic chemotherapy across all tumor stages compared to patients aged 65-75 years. The odds ratios ranged from 7.98 for stage I tumors to 2.30 for stage III tumors (JAMA Surgery 2017, Jan 25. doi:10.1001/jamasurg.2016.5050).
“Furthermore, young and middle-aged adults were 2.5 times more likely to receive multiagent chemotherapy regimens and most patients with information on chemotherapy regimens underwent multiagent regimens, suggesting a tendency toward more intense treatments,” wrote Janna Manjelievskaia, MPH, of Walter Reed National Military Medical Center, and coauthors.*
However, they found that there was no significant difference in survival between those who had surgery and chemotherapy compared to those who had surgery alone, across age groups and tumor stage.
They did note greater overall survival among middle-aged patients with stage I and stage IV disease who were treated with surgery alone, compared to their older counterparts. Younger patients with stage III disease who received surgery alone also had slightly better survival than did older patients.
“The study suggests that more use of chemotherapy in younger patients did not result in additional survival benefits,” the authors wrote.
While national guidelines advise that selected patients with stage II disease – those with inadequately sampled nodes, T3 lesions or poorly differentiated histology – can be considered for adjuvant chemotherapy, the authors argued there is no solid evidence for the effectiveness of chemotherapy in these patients.
“Patients with cancer who receive chemotherapy are vulnerable to its toxicity and adverse effects and may have reduced quality of life,” they wrote. “As a result, patients may undergo decreased physical, functional, emotional, and social well-being, although these changes might be mitigated over time.”
Given the additional economic and financial cost of adjuvant chemotherapy, the authors called for further research to evaluate the appropriate use of chemotherapy in colon cancer.
The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, and the National Cancer Institute supported the study. No conflicts of interest were declared.
* This story was updated on 2/6/2107
The study by Manjelievskaia et al. is a call for action, and invites contemplation and in-depth study. Appropriate treatment is vital for a patient’s survival, but excess treatment may increase complications and is a poor stewardship of health care funds.
Further investigation of the discrepancies in stage II would be worthwhile, and additional research on the age discrepancies in stage I disease would not only be interesting but also mandatory. Colorectal cancer tumor boards frequently concentrate on the complex care of rectal cancer and metastatic colon cancer. This is also a clear call for improved oversight of chemotherapy for colon cancer.
Tonia M. Young-Fadok, MD, is at the Mayo Clinic, Phoenix, Ariz. These comments are exerpts from an accompanying editorial (JAMA Surg. 2017, Jan 25. doi: 10.1001/jamasurg.2016.5051). No conflicts of interest were declared.
The study by Manjelievskaia et al. is a call for action, and invites contemplation and in-depth study. Appropriate treatment is vital for a patient’s survival, but excess treatment may increase complications and is a poor stewardship of health care funds.
Further investigation of the discrepancies in stage II would be worthwhile, and additional research on the age discrepancies in stage I disease would not only be interesting but also mandatory. Colorectal cancer tumor boards frequently concentrate on the complex care of rectal cancer and metastatic colon cancer. This is also a clear call for improved oversight of chemotherapy for colon cancer.
Tonia M. Young-Fadok, MD, is at the Mayo Clinic, Phoenix, Ariz. These comments are exerpts from an accompanying editorial (JAMA Surg. 2017, Jan 25. doi: 10.1001/jamasurg.2016.5051). No conflicts of interest were declared.
The study by Manjelievskaia et al. is a call for action, and invites contemplation and in-depth study. Appropriate treatment is vital for a patient’s survival, but excess treatment may increase complications and is a poor stewardship of health care funds.
Further investigation of the discrepancies in stage II would be worthwhile, and additional research on the age discrepancies in stage I disease would not only be interesting but also mandatory. Colorectal cancer tumor boards frequently concentrate on the complex care of rectal cancer and metastatic colon cancer. This is also a clear call for improved oversight of chemotherapy for colon cancer.
Tonia M. Young-Fadok, MD, is at the Mayo Clinic, Phoenix, Ariz. These comments are exerpts from an accompanying editorial (JAMA Surg. 2017, Jan 25. doi: 10.1001/jamasurg.2016.5051). No conflicts of interest were declared.
Adjuvant chemotherapy may be overused among younger patients with colon cancer, without clear evidence of survival benefit over surgery alone, according to a report in JAMA Surgery.
Using data from 3,143 patients with histologically confirmed primary colon adenocarcinoma in the U.S. Department of Defense’s Central Cancer Registry and Military Heath System medical claims databases, researchers compared overall survival in those who underwent surgery and adjuvant chemotherapy to those who underwent surgery alone.
They found patients aged 18-49 years were up to eight times more likely to receive postoperative systemic chemotherapy across all tumor stages compared to patients aged 65-75 years. The odds ratios ranged from 7.98 for stage I tumors to 2.30 for stage III tumors (JAMA Surgery 2017, Jan 25. doi:10.1001/jamasurg.2016.5050).
“Furthermore, young and middle-aged adults were 2.5 times more likely to receive multiagent chemotherapy regimens and most patients with information on chemotherapy regimens underwent multiagent regimens, suggesting a tendency toward more intense treatments,” wrote Janna Manjelievskaia, MPH, of Walter Reed National Military Medical Center, and coauthors.*
However, they found that there was no significant difference in survival between those who had surgery and chemotherapy compared to those who had surgery alone, across age groups and tumor stage.
They did note greater overall survival among middle-aged patients with stage I and stage IV disease who were treated with surgery alone, compared to their older counterparts. Younger patients with stage III disease who received surgery alone also had slightly better survival than did older patients.
“The study suggests that more use of chemotherapy in younger patients did not result in additional survival benefits,” the authors wrote.
While national guidelines advise that selected patients with stage II disease – those with inadequately sampled nodes, T3 lesions or poorly differentiated histology – can be considered for adjuvant chemotherapy, the authors argued there is no solid evidence for the effectiveness of chemotherapy in these patients.
“Patients with cancer who receive chemotherapy are vulnerable to its toxicity and adverse effects and may have reduced quality of life,” they wrote. “As a result, patients may undergo decreased physical, functional, emotional, and social well-being, although these changes might be mitigated over time.”
Given the additional economic and financial cost of adjuvant chemotherapy, the authors called for further research to evaluate the appropriate use of chemotherapy in colon cancer.
The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, and the National Cancer Institute supported the study. No conflicts of interest were declared.
* This story was updated on 2/6/2107
Adjuvant chemotherapy may be overused among younger patients with colon cancer, without clear evidence of survival benefit over surgery alone, according to a report in JAMA Surgery.
Using data from 3,143 patients with histologically confirmed primary colon adenocarcinoma in the U.S. Department of Defense’s Central Cancer Registry and Military Heath System medical claims databases, researchers compared overall survival in those who underwent surgery and adjuvant chemotherapy to those who underwent surgery alone.
They found patients aged 18-49 years were up to eight times more likely to receive postoperative systemic chemotherapy across all tumor stages compared to patients aged 65-75 years. The odds ratios ranged from 7.98 for stage I tumors to 2.30 for stage III tumors (JAMA Surgery 2017, Jan 25. doi:10.1001/jamasurg.2016.5050).
“Furthermore, young and middle-aged adults were 2.5 times more likely to receive multiagent chemotherapy regimens and most patients with information on chemotherapy regimens underwent multiagent regimens, suggesting a tendency toward more intense treatments,” wrote Janna Manjelievskaia, MPH, of Walter Reed National Military Medical Center, and coauthors.*
However, they found that there was no significant difference in survival between those who had surgery and chemotherapy compared to those who had surgery alone, across age groups and tumor stage.
They did note greater overall survival among middle-aged patients with stage I and stage IV disease who were treated with surgery alone, compared to their older counterparts. Younger patients with stage III disease who received surgery alone also had slightly better survival than did older patients.
“The study suggests that more use of chemotherapy in younger patients did not result in additional survival benefits,” the authors wrote.
While national guidelines advise that selected patients with stage II disease – those with inadequately sampled nodes, T3 lesions or poorly differentiated histology – can be considered for adjuvant chemotherapy, the authors argued there is no solid evidence for the effectiveness of chemotherapy in these patients.
“Patients with cancer who receive chemotherapy are vulnerable to its toxicity and adverse effects and may have reduced quality of life,” they wrote. “As a result, patients may undergo decreased physical, functional, emotional, and social well-being, although these changes might be mitigated over time.”
Given the additional economic and financial cost of adjuvant chemotherapy, the authors called for further research to evaluate the appropriate use of chemotherapy in colon cancer.
The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, and the National Cancer Institute supported the study. No conflicts of interest were declared.
* This story was updated on 2/6/2107
FROM JAMA SURGERY
Key clinical point: Adjuvant chemotherapy may be overused among younger patients with colon cancer, without clear evidence of a survival benefit over surgery alone.
Major finding: Younger patients with colon cancer are between two and eight times more likely to have adjuvant chemotherapy in addition to surgery compared to older patients with colon cancer.
Data source: A cohort study of 3,143 patients with histologically confirmed primary colon adenocarcinoma.
Disclosures: The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, and the National Cancer Institute supported the study. No conflicts of interest were declared.
ACA repeal would impact adults at higher risk of chronic disease
Individuals at risk of losing health insurance with a potential repeal of the Affordable Care Act have significantly higher rates of self-reported poor health and are more likely to have certain chronic diseases, according to a research letter published Jan. 20 in JAMA Internal Medicine.
Researchers looked at data from the National Health Interview Survey, focusing on the three groups of adults under 65 years who would be most likely to lose their health insurance if the ACA were repealed: those with incomes below 400% of the federal poverty level (FPL) who purchased insurance through the health insurance exchanges, childless adults with incomes below 138% of the FPL who gained coverage via expanded Medicaid, and Medicaid-enrolled parents or adults in families with children who did not receive disability insurance and whose income was 50%-138% of the FPL.
“Approximately 20 million individuals have gained health insurance under the Affordable Care Act (ACA), including young adults covered under parental insurance, those purchasing private insurance on exchanges, and those covered through state Medicaid expansion,” wrote Pinar Karaca-Mandic, PhD, of the University of Minnesota School of Public Health, Minneapolis, and her coauthors. “As of mid-2016, 10.4 million individuals had private insurance policies through the exchanges, of whom 84% had incomes below 400% of the federal poverty level (FPL) and received premium tax credits.”
Compared with adults under 65 who had employer-sponsored health insurance, adults in these three groups were significantly more likely to self-report their health as “fair or poor” (JAMA Intern Med. 2017 Jan 20. doi: 10.1001/jamainternmed.2016.9541).
Adults without children and with incomes below 138% of the federal poverty level also had a significantly greater incidence of hypertension, coronary heart disease, cancer, diabetes, stroke, or any heart condition, compared with individuals with employer-sponsored insurance.
They were also significantly more likely to have visited a physician 10 or more times or visited the emergency department at least twice in the past year, and to have undergone surgery in the past year.
“Our analysis highlights the socioeconomic vulnerability and rates of chronic diseases and health care utilization of individuals at risk to lose health insurance if the ACA is modified or repealed,” according to Dr. Karaca-Mandic. “These consequences point to the challenges Congress should address before enacting new health care legislation.”
The study was supported by the NIH Early Independence Award. One author declared consulting fees from the pharmaceutical industry, and another declared private sector support through Yale University. No other conflicts of interest were declared.
We believe that health care is a right, not a privilege, and all Americans should have access to high-quality health care, regardless of their income or personal circumstances. The United States has the most advanced health care system in the world by many criteria, but access to the system is uneven. Even with the ACA, 29 million people were without health insurance coverage for the entire 2015 calendar year.
The central questions remain of how to attain a health care system that is accessible to all Americans, that provides needed care while avoiding unnecessary care, and that delivers care at an affordable and sustainable price. The next steps are to build on the progress that has been made, which will require further improvements in health insurance coverage, the ability of people to obtain needed medical care regardless of income, and a continued shift away from fee-for-service medicine. The future is about universal health care coverage and access, improved quality, and payment reforms that will have a meaningful impact on the costs of health care and prescription drugs.
Rita F. Redberg, MD, is the editor of JAMA Internal Medicine, Robert Steinbrook, MD, is an editor at large, and Mitchell H. Katz, MD, is deputy editor. Their comments are taken from an accompanying editorial (JAMA Intern Med 2017 Jan 20. doi: 10.1001/jamainternmed.2016.9542). No conflicts of interest were declared.
We believe that health care is a right, not a privilege, and all Americans should have access to high-quality health care, regardless of their income or personal circumstances. The United States has the most advanced health care system in the world by many criteria, but access to the system is uneven. Even with the ACA, 29 million people were without health insurance coverage for the entire 2015 calendar year.
The central questions remain of how to attain a health care system that is accessible to all Americans, that provides needed care while avoiding unnecessary care, and that delivers care at an affordable and sustainable price. The next steps are to build on the progress that has been made, which will require further improvements in health insurance coverage, the ability of people to obtain needed medical care regardless of income, and a continued shift away from fee-for-service medicine. The future is about universal health care coverage and access, improved quality, and payment reforms that will have a meaningful impact on the costs of health care and prescription drugs.
Rita F. Redberg, MD, is the editor of JAMA Internal Medicine, Robert Steinbrook, MD, is an editor at large, and Mitchell H. Katz, MD, is deputy editor. Their comments are taken from an accompanying editorial (JAMA Intern Med 2017 Jan 20. doi: 10.1001/jamainternmed.2016.9542). No conflicts of interest were declared.
We believe that health care is a right, not a privilege, and all Americans should have access to high-quality health care, regardless of their income or personal circumstances. The United States has the most advanced health care system in the world by many criteria, but access to the system is uneven. Even with the ACA, 29 million people were without health insurance coverage for the entire 2015 calendar year.
The central questions remain of how to attain a health care system that is accessible to all Americans, that provides needed care while avoiding unnecessary care, and that delivers care at an affordable and sustainable price. The next steps are to build on the progress that has been made, which will require further improvements in health insurance coverage, the ability of people to obtain needed medical care regardless of income, and a continued shift away from fee-for-service medicine. The future is about universal health care coverage and access, improved quality, and payment reforms that will have a meaningful impact on the costs of health care and prescription drugs.
Rita F. Redberg, MD, is the editor of JAMA Internal Medicine, Robert Steinbrook, MD, is an editor at large, and Mitchell H. Katz, MD, is deputy editor. Their comments are taken from an accompanying editorial (JAMA Intern Med 2017 Jan 20. doi: 10.1001/jamainternmed.2016.9542). No conflicts of interest were declared.
Individuals at risk of losing health insurance with a potential repeal of the Affordable Care Act have significantly higher rates of self-reported poor health and are more likely to have certain chronic diseases, according to a research letter published Jan. 20 in JAMA Internal Medicine.
Researchers looked at data from the National Health Interview Survey, focusing on the three groups of adults under 65 years who would be most likely to lose their health insurance if the ACA were repealed: those with incomes below 400% of the federal poverty level (FPL) who purchased insurance through the health insurance exchanges, childless adults with incomes below 138% of the FPL who gained coverage via expanded Medicaid, and Medicaid-enrolled parents or adults in families with children who did not receive disability insurance and whose income was 50%-138% of the FPL.
“Approximately 20 million individuals have gained health insurance under the Affordable Care Act (ACA), including young adults covered under parental insurance, those purchasing private insurance on exchanges, and those covered through state Medicaid expansion,” wrote Pinar Karaca-Mandic, PhD, of the University of Minnesota School of Public Health, Minneapolis, and her coauthors. “As of mid-2016, 10.4 million individuals had private insurance policies through the exchanges, of whom 84% had incomes below 400% of the federal poverty level (FPL) and received premium tax credits.”
Compared with adults under 65 who had employer-sponsored health insurance, adults in these three groups were significantly more likely to self-report their health as “fair or poor” (JAMA Intern Med. 2017 Jan 20. doi: 10.1001/jamainternmed.2016.9541).
Adults without children and with incomes below 138% of the federal poverty level also had a significantly greater incidence of hypertension, coronary heart disease, cancer, diabetes, stroke, or any heart condition, compared with individuals with employer-sponsored insurance.
They were also significantly more likely to have visited a physician 10 or more times or visited the emergency department at least twice in the past year, and to have undergone surgery in the past year.
“Our analysis highlights the socioeconomic vulnerability and rates of chronic diseases and health care utilization of individuals at risk to lose health insurance if the ACA is modified or repealed,” according to Dr. Karaca-Mandic. “These consequences point to the challenges Congress should address before enacting new health care legislation.”
The study was supported by the NIH Early Independence Award. One author declared consulting fees from the pharmaceutical industry, and another declared private sector support through Yale University. No other conflicts of interest were declared.
Individuals at risk of losing health insurance with a potential repeal of the Affordable Care Act have significantly higher rates of self-reported poor health and are more likely to have certain chronic diseases, according to a research letter published Jan. 20 in JAMA Internal Medicine.
Researchers looked at data from the National Health Interview Survey, focusing on the three groups of adults under 65 years who would be most likely to lose their health insurance if the ACA were repealed: those with incomes below 400% of the federal poverty level (FPL) who purchased insurance through the health insurance exchanges, childless adults with incomes below 138% of the FPL who gained coverage via expanded Medicaid, and Medicaid-enrolled parents or adults in families with children who did not receive disability insurance and whose income was 50%-138% of the FPL.
“Approximately 20 million individuals have gained health insurance under the Affordable Care Act (ACA), including young adults covered under parental insurance, those purchasing private insurance on exchanges, and those covered through state Medicaid expansion,” wrote Pinar Karaca-Mandic, PhD, of the University of Minnesota School of Public Health, Minneapolis, and her coauthors. “As of mid-2016, 10.4 million individuals had private insurance policies through the exchanges, of whom 84% had incomes below 400% of the federal poverty level (FPL) and received premium tax credits.”
Compared with adults under 65 who had employer-sponsored health insurance, adults in these three groups were significantly more likely to self-report their health as “fair or poor” (JAMA Intern Med. 2017 Jan 20. doi: 10.1001/jamainternmed.2016.9541).
Adults without children and with incomes below 138% of the federal poverty level also had a significantly greater incidence of hypertension, coronary heart disease, cancer, diabetes, stroke, or any heart condition, compared with individuals with employer-sponsored insurance.
They were also significantly more likely to have visited a physician 10 or more times or visited the emergency department at least twice in the past year, and to have undergone surgery in the past year.
“Our analysis highlights the socioeconomic vulnerability and rates of chronic diseases and health care utilization of individuals at risk to lose health insurance if the ACA is modified or repealed,” according to Dr. Karaca-Mandic. “These consequences point to the challenges Congress should address before enacting new health care legislation.”
The study was supported by the NIH Early Independence Award. One author declared consulting fees from the pharmaceutical industry, and another declared private sector support through Yale University. No other conflicts of interest were declared.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Adults at risk of losing health coverage if the Affordable Care Act were repealed have significantly higher rates of poor health and are more likely to suffer chronic diseases.
Major finding: Individuals at risk of losing health insurance with the rollback of the Affordable Care Act are significantly more likely than individuals with employer-sponsored health insurance to self-report their health as “fair or poor.”
Data source: An analysis of data from the population-based National Health Interview Survey.
Disclosures: The study was supported by the NIH Early Independence Award. One author declared consulting fees from the pharmaceutical industry, and another declared private sector support through Yale University. No other conflicts of interest were declared.
More restrictive hemoglobin threshold advised
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
These recommendations are very helpful and are now part of standard ICU care in several centers. Our experience in clinical practice has shown that even patients supported with extracorporeal membrane oxygenation (ECMO) for acute lung failure or as a bridge to lung transplantation on VV ECMO can safely tolerate a lower transfusion threshold (7-8g/dL.) Future well-designed trials are needed to advocate its safety in patients supported with extracorporeal life support technologies.
These recommendations are very helpful and are now part of standard ICU care in several centers. Our experience in clinical practice has shown that even patients supported with extracorporeal membrane oxygenation (ECMO) for acute lung failure or as a bridge to lung transplantation on VV ECMO can safely tolerate a lower transfusion threshold (7-8g/dL.) Future well-designed trials are needed to advocate its safety in patients supported with extracorporeal life support technologies.
These recommendations are very helpful and are now part of standard ICU care in several centers. Our experience in clinical practice has shown that even patients supported with extracorporeal membrane oxygenation (ECMO) for acute lung failure or as a bridge to lung transplantation on VV ECMO can safely tolerate a lower transfusion threshold (7-8g/dL.) Future well-designed trials are needed to advocate its safety in patients supported with extracorporeal life support technologies.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
New guidelines on red blood cell blood transfusion recommend a restrictive threshold in which transfusion is not indicated until the hemoglobin level is 7-8 g/dL for most patients, finding that it is safe in most clinical settings.
The updated clinical practice guidelines on transfusion thresholds and storage from the AABB (formerly known as the American Association of Blood Banks), also note that red blood cell units can be used at any time within their licensed dating period, rather than a preference being given to fresher units less than 10 days old.
The guidelines, published online Oct. 12 in JAMA, are an update of the 2012 transfusion guidelines, and are a response to a more than doubling of the number of patients since enrolled in randomized controlled trials of red blood cell transfusions.
The AABB’s clinical transfusion medicine committee, led by Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School, New Brunswick, N.J., analyzed data from 31 randomized controlled trials of 12,587 participants, which compared restrictive transfusion thresholds of 7-8 g/dL to more liberal thresholds of 9-10 g/dL.
This analysis showed that the use of restrictive transfusion protocols was associated with an absolute difference in 30-day mortality of three fewer deaths compared to the more liberal thresholds. There was no significant difference in 30-day mortality in trials that compared a threshold of 8-9 g/dL to a threshold of less than 7 g/dL (JAMA 2016, Oct 12. doi: 10.1001/jama.2016.9185).
“For all other outcomes evaluated, there was no evidence to suggest that patients were harmed by restrictive transfusion protocols, although the quality of the evidence was low for the outcomes of congestive heart failure and rebleeding,” the authors reported.
Based on these findings, they recommended a restrictive red blood cell transfusion threshold, in which transfusion is not indicated until the hemoglobin level is 7 g/dL for hospitalized adult patients who are hemodynamically stable, including critically ill patients.
However for patients undergoing orthopedic or cardiac surgery, or those with preexisting cardiovascular disease, they advised a threshold of 8 g/dL for initiating a red blood cell transfusion.
They also stressed that these recommendations did not apply to patients with acute coronary syndrome, those with severe thrombocytopenia, those treated for hematologic or oncologic disorders who at risk of bleeding, and those with chronic transfusion–dependent anemia, citing a lack of quality randomized controlled trial evidence.
The guideline authors examined the issue of the optimal length of time that red blood cell units should be stored, pointing out that there is currently no formal guidance on the optimal period of red blood cell storage prior to transfusion.
While units of red blood cells can be stored for up to 42 days, the committee said there was some evidence that longer storage may be associated with adverse transfusion outcomes.
“The RBCs stored for longer periods have decreased ability to deliver oxygen due to decreased levels of 2,3-diphsophoglycerate, decreased nitric oxide metabolism, alterations of the RBC membrane leading to increased rigidity, and increased RBC endothelial adherence,” they wrote.
Despite this, the review of 13 randomized controlled trials examining the effect of storage duration found no evidence that fresher units had any impact on mortality compared to standard issue units, nor were there any more adverse events with the standard issue units.
The absolute difference in 30-day mortality was four more deaths per 1,000 with fresher blood, and there was a higher risk of nosocomial infections among patients who received fresher red blood cell units although the authors said the quality of evidence was low.
They therefore recommended that no preference be given to fresher red blood cell units, and that all patients be treated with units chosen at any point within their licensed dating period.
Guideline development was supported by AABB. Four authors declared grants, fees, stock options or consultancies from pharmaceutical companies, but no other conflicts of interest were declared.
January 2017: Click for Credit
Here are 5 articles in the January issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Gluten-free Adherence Triples While Celiac Disease Prevalence Remains Stable
To take the posttest, go to: http://bit.ly/2h2LFDu
Expires September 6, 2017
2. Fluoxetine Appears Safer for Bone Health in At-risk Older Patients
To take the posttest, go to: http://bit.ly/2he1FTD
Expires September 15, 2017
3. High Free T4 Levels Linked to Sudden Cardiac Death
To take the posttest, go to: http://bit.ly/2gMJqUz
Expires September 16, 2017
4. Morning Sickness Linked to Lower Risk for Pregnancy Loss
To take the posttest, go to: http://bit.ly/2uaWMkH
Expires September 26, 2017
5. Anxiety, Depression May Precede Parkinson's by 25 Years
To take the posttest, go to: http://bit.ly/2gMFQtr
Expires September 27, 2017
Here are 5 articles in the January issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Gluten-free Adherence Triples While Celiac Disease Prevalence Remains Stable
To take the posttest, go to: http://bit.ly/2h2LFDu
Expires September 6, 2017
2. Fluoxetine Appears Safer for Bone Health in At-risk Older Patients
To take the posttest, go to: http://bit.ly/2he1FTD
Expires September 15, 2017
3. High Free T4 Levels Linked to Sudden Cardiac Death
To take the posttest, go to: http://bit.ly/2gMJqUz
Expires September 16, 2017
4. Morning Sickness Linked to Lower Risk for Pregnancy Loss
To take the posttest, go to: http://bit.ly/2uaWMkH
Expires September 26, 2017
5. Anxiety, Depression May Precede Parkinson's by 25 Years
To take the posttest, go to: http://bit.ly/2gMFQtr
Expires September 27, 2017
Here are 5 articles in the January issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Gluten-free Adherence Triples While Celiac Disease Prevalence Remains Stable
To take the posttest, go to: http://bit.ly/2h2LFDu
Expires September 6, 2017
2. Fluoxetine Appears Safer for Bone Health in At-risk Older Patients
To take the posttest, go to: http://bit.ly/2he1FTD
Expires September 15, 2017
3. High Free T4 Levels Linked to Sudden Cardiac Death
To take the posttest, go to: http://bit.ly/2gMJqUz
Expires September 16, 2017
4. Morning Sickness Linked to Lower Risk for Pregnancy Loss
To take the posttest, go to: http://bit.ly/2uaWMkH
Expires September 26, 2017
5. Anxiety, Depression May Precede Parkinson's by 25 Years
To take the posttest, go to: http://bit.ly/2gMFQtr
Expires September 27, 2017
AGA Clinical Practice Update: Treatment for severe alcohol hepatitis challenging
Acute alcoholic hepatitis carries a high risk of mortality, yet only a minority of patients admitted to the hospital with the condition receive appropriate treatment, said the authors of an expert review.
Writing in the January 2017 issue of Clinical Gastroenterology and Hepatology, Mack C. Mitchell Jr., MD, of the University of Texas Southwestern Medical Center, Dallas, and Craig J. McClain, MD, of the University of Louisville (Ky.), described the challenges associated with treating acute alcoholic hepatitis and its consequences.
Acute alcohol hepatitis develops in heavy drinkers and presents with rapid onset of malaise, anorexia, tender hepatomegaly, and features of the systemic inflammatory response syndrome. Patients with alcoholic hepatitis also are at high risk of nutritional deficiency, infection, acute kidney injury, and multiorgan failure.
The two most widely used therapies are glucocorticoids – generally considered the standard of care for severe alcoholic hepatitis – and the phosphodiesterase inhibitor pentoxifylline (Clin Gastroenterol Hepatol. 2017. doi: 10.1016/j.cgh.2016.08.047).
“Although in its most severe form AH has a high short-term mortality rate if untreated, in 2011, only 28% of more than 1,600 patients admitted to U.S. hospitals were treated with glucocorticoids and 17% with pentoxifylline (PTX), suggesting a lack of widespread confidence in the two most frequently used therapies for AH,” the authors wrote.
Both drugs work by addressing the underlying inflammation that plays a key role in liver injury, but the evidence for both is mixed: A 2008 Cochrane systematic review of 15 trials concluded there was no benefit from glucocorticoids, largely because of substantial variability in bias across the trials, while two meta-analyses of pentoxifylline trials concluded that there were no differences in short-term mortality between those who received it and those who did not.
Some patients are unsuitable for glucocorticoids and others may develop resistance. There is also the possibility that, while glucocorticoids may improve short-term survival, the associated increase in infection risk removes that advantage at 90 days and 1 year after diagnosis. These infections, in turn, often precede the development of acute kidney injury and multiorgan failure.
The authors, however, did suggest that the approach of very high, short-term bursts of glucocorticoids to induce “immune paralysis” – an approach taken for lupus nephritis – might be considered.
They stressed that abstinence was the cornerstone of treatment for acute alcoholic hepatitis, with studies showing that patients with alcoholic hepatitis who resume heavy drinking have significantly worse outcomes than those who don’t.
“Although abstinence is important at all stages, it is particularly important to emphasize abstinence beyond 90 days when many patients are regaining normal functioning,” Dr. Mitchell and Dr. McClain wrote.
Infection, kidney injury, and malnutrition are all significant concerns in patients with acute alcoholic hepatitis.
With respect to infection, the authors said considerable suspicion is required to pick up bacterial and fungal infections, as patients may not always have a fever and an elevated white blood cell count is an unreliable indicator. Infection also can lead to acute kidney injury.
Malnutrition is not only common in patients with alcohol hepatitis, but it has a significant negative impact on recovery. All patients should be encouraged to meet nutritional goals as early as possible, but just how to achieve this is controversial, the authors stressed.
For example, one study suggested that enteral nutrition was as good as glucocorticoids in reducing 28-day mortality, while another found enteral nutrition via nasogastric tube – in addition to glucocorticoids – was no better than glucocorticoids alone. “Whether [nasogastric] tubes should be used to provide enteral nutrition is a subject of controversy,” the authors wrote. “Normal- to high-protein diets are safe and do not increase the risk of encephalopathy in patients with AH.”
No conflicts of interest were declared.
Acute alcoholic hepatitis carries a high risk of mortality, yet only a minority of patients admitted to the hospital with the condition receive appropriate treatment, said the authors of an expert review.
Writing in the January 2017 issue of Clinical Gastroenterology and Hepatology, Mack C. Mitchell Jr., MD, of the University of Texas Southwestern Medical Center, Dallas, and Craig J. McClain, MD, of the University of Louisville (Ky.), described the challenges associated with treating acute alcoholic hepatitis and its consequences.
Acute alcohol hepatitis develops in heavy drinkers and presents with rapid onset of malaise, anorexia, tender hepatomegaly, and features of the systemic inflammatory response syndrome. Patients with alcoholic hepatitis also are at high risk of nutritional deficiency, infection, acute kidney injury, and multiorgan failure.
The two most widely used therapies are glucocorticoids – generally considered the standard of care for severe alcoholic hepatitis – and the phosphodiesterase inhibitor pentoxifylline (Clin Gastroenterol Hepatol. 2017. doi: 10.1016/j.cgh.2016.08.047).
“Although in its most severe form AH has a high short-term mortality rate if untreated, in 2011, only 28% of more than 1,600 patients admitted to U.S. hospitals were treated with glucocorticoids and 17% with pentoxifylline (PTX), suggesting a lack of widespread confidence in the two most frequently used therapies for AH,” the authors wrote.
Both drugs work by addressing the underlying inflammation that plays a key role in liver injury, but the evidence for both is mixed: A 2008 Cochrane systematic review of 15 trials concluded there was no benefit from glucocorticoids, largely because of substantial variability in bias across the trials, while two meta-analyses of pentoxifylline trials concluded that there were no differences in short-term mortality between those who received it and those who did not.
Some patients are unsuitable for glucocorticoids and others may develop resistance. There is also the possibility that, while glucocorticoids may improve short-term survival, the associated increase in infection risk removes that advantage at 90 days and 1 year after diagnosis. These infections, in turn, often precede the development of acute kidney injury and multiorgan failure.
The authors, however, did suggest that the approach of very high, short-term bursts of glucocorticoids to induce “immune paralysis” – an approach taken for lupus nephritis – might be considered.
They stressed that abstinence was the cornerstone of treatment for acute alcoholic hepatitis, with studies showing that patients with alcoholic hepatitis who resume heavy drinking have significantly worse outcomes than those who don’t.
“Although abstinence is important at all stages, it is particularly important to emphasize abstinence beyond 90 days when many patients are regaining normal functioning,” Dr. Mitchell and Dr. McClain wrote.
Infection, kidney injury, and malnutrition are all significant concerns in patients with acute alcoholic hepatitis.
With respect to infection, the authors said considerable suspicion is required to pick up bacterial and fungal infections, as patients may not always have a fever and an elevated white blood cell count is an unreliable indicator. Infection also can lead to acute kidney injury.
Malnutrition is not only common in patients with alcohol hepatitis, but it has a significant negative impact on recovery. All patients should be encouraged to meet nutritional goals as early as possible, but just how to achieve this is controversial, the authors stressed.
For example, one study suggested that enteral nutrition was as good as glucocorticoids in reducing 28-day mortality, while another found enteral nutrition via nasogastric tube – in addition to glucocorticoids – was no better than glucocorticoids alone. “Whether [nasogastric] tubes should be used to provide enteral nutrition is a subject of controversy,” the authors wrote. “Normal- to high-protein diets are safe and do not increase the risk of encephalopathy in patients with AH.”
No conflicts of interest were declared.
Acute alcoholic hepatitis carries a high risk of mortality, yet only a minority of patients admitted to the hospital with the condition receive appropriate treatment, said the authors of an expert review.
Writing in the January 2017 issue of Clinical Gastroenterology and Hepatology, Mack C. Mitchell Jr., MD, of the University of Texas Southwestern Medical Center, Dallas, and Craig J. McClain, MD, of the University of Louisville (Ky.), described the challenges associated with treating acute alcoholic hepatitis and its consequences.
Acute alcohol hepatitis develops in heavy drinkers and presents with rapid onset of malaise, anorexia, tender hepatomegaly, and features of the systemic inflammatory response syndrome. Patients with alcoholic hepatitis also are at high risk of nutritional deficiency, infection, acute kidney injury, and multiorgan failure.
The two most widely used therapies are glucocorticoids – generally considered the standard of care for severe alcoholic hepatitis – and the phosphodiesterase inhibitor pentoxifylline (Clin Gastroenterol Hepatol. 2017. doi: 10.1016/j.cgh.2016.08.047).
“Although in its most severe form AH has a high short-term mortality rate if untreated, in 2011, only 28% of more than 1,600 patients admitted to U.S. hospitals were treated with glucocorticoids and 17% with pentoxifylline (PTX), suggesting a lack of widespread confidence in the two most frequently used therapies for AH,” the authors wrote.
Both drugs work by addressing the underlying inflammation that plays a key role in liver injury, but the evidence for both is mixed: A 2008 Cochrane systematic review of 15 trials concluded there was no benefit from glucocorticoids, largely because of substantial variability in bias across the trials, while two meta-analyses of pentoxifylline trials concluded that there were no differences in short-term mortality between those who received it and those who did not.
Some patients are unsuitable for glucocorticoids and others may develop resistance. There is also the possibility that, while glucocorticoids may improve short-term survival, the associated increase in infection risk removes that advantage at 90 days and 1 year after diagnosis. These infections, in turn, often precede the development of acute kidney injury and multiorgan failure.
The authors, however, did suggest that the approach of very high, short-term bursts of glucocorticoids to induce “immune paralysis” – an approach taken for lupus nephritis – might be considered.
They stressed that abstinence was the cornerstone of treatment for acute alcoholic hepatitis, with studies showing that patients with alcoholic hepatitis who resume heavy drinking have significantly worse outcomes than those who don’t.
“Although abstinence is important at all stages, it is particularly important to emphasize abstinence beyond 90 days when many patients are regaining normal functioning,” Dr. Mitchell and Dr. McClain wrote.
Infection, kidney injury, and malnutrition are all significant concerns in patients with acute alcoholic hepatitis.
With respect to infection, the authors said considerable suspicion is required to pick up bacterial and fungal infections, as patients may not always have a fever and an elevated white blood cell count is an unreliable indicator. Infection also can lead to acute kidney injury.
Malnutrition is not only common in patients with alcohol hepatitis, but it has a significant negative impact on recovery. All patients should be encouraged to meet nutritional goals as early as possible, but just how to achieve this is controversial, the authors stressed.
For example, one study suggested that enteral nutrition was as good as glucocorticoids in reducing 28-day mortality, while another found enteral nutrition via nasogastric tube – in addition to glucocorticoids – was no better than glucocorticoids alone. “Whether [nasogastric] tubes should be used to provide enteral nutrition is a subject of controversy,” the authors wrote. “Normal- to high-protein diets are safe and do not increase the risk of encephalopathy in patients with AH.”
No conflicts of interest were declared.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Teens see marijuana as less harmful after legalization
The legalization of recreational marijuana use is associated with an increase in use of the drug among adolescents, who also perceive it as being less harmful, a new study published online suggests.
In the study, Magdalena Cerdá, DrPH, MPH, and her associates used data from the Monitoring the Future study – a national, annual, cross-sectional survey conducted by the University of Michigan, Ann Arbor, that looks at attitudes about drug use among students in 8th, 10th, and 12th grade. The investigators analyzed the data gathered from 2010 to 2015 in an effort to compare attitudes about marijuana and its use before and after legalization in Washington and Colorado, and in states that did not legalize.
“While the increase in marijuana use among 8th graders in Washington was not significantly greater than zero, the significant decrease in use among 8th graders in states [with no recreational marijuana laws] suggests that if there had been no legalization in Washington, then marijuana use among 8th graders in this state would decrease rather than remain stable, as it did,” wrote Dr. Cerdà of the emergency medicine department at the University of California, Davis, in Sacramento, and her coauthors. “Specifically, the prevalence of regular users of marijuana increased and the prevalence of nonusers decreased; no change was observed among occasional users.”
Legalization, however, did not appear to significantly affect perceived harmfulness or use among 12th graders in any states, nor were there any significant changes after legalization among adolescents in all three grades surveyed in Colorado.
The authors noted that Colorado had a well-developed medical marijuana program in place, with substantial advertising, which might account for the lack of apparent impact of legalization for recreational use.
Commenting on the overall impact of legalization on use, the authors suggested that, besides reducing stigma and perceptions of risk, the legalization of recreational marijuana might have increased availability and potentially decreased the price, which might have led to the increase in use.
Given this, they cautiously proposed increased investment in evidence-based adolescent substance use prevention programs in states that choose to legalize recreational marijuana.
Dr. Cerdá and her associates cited several limitations. For example, the use of marijuana was self reported, and the Monitoring the Future results might have missed adolescents who were either absent from school when the survey was taken or had dropped out.
The study was supported by the National Institute on Drug Abuse, the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism, and the New York State Psychiatric Institute. No conflicts of interest were declared.
The legalization of marijuana complicates efforts to prevent use of the drug by young people, Wayne Hall, PhD, and Megan Weier wrote in an accompanying editorial (JAMA Pediatr. 2016 Dec 27. doi: 10.1001/jamapediatrics.2016.3917).
“The challenge for health educators will be in acknowledging that the acute adverse effects of marijuana use are modest by comparison with those of alcohol or heroin, while persuading young people that they can experience adverse effects, especially if they begin use in their teens and use daily throughout young adult life,” Dr. Hall and Ms. Weir wrote.
Users of the drug, they said, should be told that the risk of a collision while driving while intoxicated doubles, “especially if they use both alcohol and marijuana.” In addition, Dr. Hall and Ms. Weier said, people who use the drug regularly should be informed that they can become dependent. “The risk for dependence is about 1 in 10 for those who ever use marijuana and 1 in 6 for those who first use in adolescence. Marijuana users also need to know that dependent users have more anxiety, depression, and psychotic disorders and are more likely to leave school early, to be unemployed as adults, and experience downward social mobility in mid-adulthood,” they wrote.
Dr. Hall and Ms. Weier are affiliated with the Centre for Youth Substance Abuse Research at Royal Brisbane and Women’s Hospital in Herston, Australia. They reported no conflicts of interest.
The legalization of marijuana complicates efforts to prevent use of the drug by young people, Wayne Hall, PhD, and Megan Weier wrote in an accompanying editorial (JAMA Pediatr. 2016 Dec 27. doi: 10.1001/jamapediatrics.2016.3917).
“The challenge for health educators will be in acknowledging that the acute adverse effects of marijuana use are modest by comparison with those of alcohol or heroin, while persuading young people that they can experience adverse effects, especially if they begin use in their teens and use daily throughout young adult life,” Dr. Hall and Ms. Weir wrote.
Users of the drug, they said, should be told that the risk of a collision while driving while intoxicated doubles, “especially if they use both alcohol and marijuana.” In addition, Dr. Hall and Ms. Weier said, people who use the drug regularly should be informed that they can become dependent. “The risk for dependence is about 1 in 10 for those who ever use marijuana and 1 in 6 for those who first use in adolescence. Marijuana users also need to know that dependent users have more anxiety, depression, and psychotic disorders and are more likely to leave school early, to be unemployed as adults, and experience downward social mobility in mid-adulthood,” they wrote.
Dr. Hall and Ms. Weier are affiliated with the Centre for Youth Substance Abuse Research at Royal Brisbane and Women’s Hospital in Herston, Australia. They reported no conflicts of interest.
The legalization of marijuana complicates efforts to prevent use of the drug by young people, Wayne Hall, PhD, and Megan Weier wrote in an accompanying editorial (JAMA Pediatr. 2016 Dec 27. doi: 10.1001/jamapediatrics.2016.3917).
“The challenge for health educators will be in acknowledging that the acute adverse effects of marijuana use are modest by comparison with those of alcohol or heroin, while persuading young people that they can experience adverse effects, especially if they begin use in their teens and use daily throughout young adult life,” Dr. Hall and Ms. Weir wrote.
Users of the drug, they said, should be told that the risk of a collision while driving while intoxicated doubles, “especially if they use both alcohol and marijuana.” In addition, Dr. Hall and Ms. Weier said, people who use the drug regularly should be informed that they can become dependent. “The risk for dependence is about 1 in 10 for those who ever use marijuana and 1 in 6 for those who first use in adolescence. Marijuana users also need to know that dependent users have more anxiety, depression, and psychotic disorders and are more likely to leave school early, to be unemployed as adults, and experience downward social mobility in mid-adulthood,” they wrote.
Dr. Hall and Ms. Weier are affiliated with the Centre for Youth Substance Abuse Research at Royal Brisbane and Women’s Hospital in Herston, Australia. They reported no conflicts of interest.
The legalization of recreational marijuana use is associated with an increase in use of the drug among adolescents, who also perceive it as being less harmful, a new study published online suggests.
In the study, Magdalena Cerdá, DrPH, MPH, and her associates used data from the Monitoring the Future study – a national, annual, cross-sectional survey conducted by the University of Michigan, Ann Arbor, that looks at attitudes about drug use among students in 8th, 10th, and 12th grade. The investigators analyzed the data gathered from 2010 to 2015 in an effort to compare attitudes about marijuana and its use before and after legalization in Washington and Colorado, and in states that did not legalize.
“While the increase in marijuana use among 8th graders in Washington was not significantly greater than zero, the significant decrease in use among 8th graders in states [with no recreational marijuana laws] suggests that if there had been no legalization in Washington, then marijuana use among 8th graders in this state would decrease rather than remain stable, as it did,” wrote Dr. Cerdà of the emergency medicine department at the University of California, Davis, in Sacramento, and her coauthors. “Specifically, the prevalence of regular users of marijuana increased and the prevalence of nonusers decreased; no change was observed among occasional users.”
Legalization, however, did not appear to significantly affect perceived harmfulness or use among 12th graders in any states, nor were there any significant changes after legalization among adolescents in all three grades surveyed in Colorado.
The authors noted that Colorado had a well-developed medical marijuana program in place, with substantial advertising, which might account for the lack of apparent impact of legalization for recreational use.
Commenting on the overall impact of legalization on use, the authors suggested that, besides reducing stigma and perceptions of risk, the legalization of recreational marijuana might have increased availability and potentially decreased the price, which might have led to the increase in use.
Given this, they cautiously proposed increased investment in evidence-based adolescent substance use prevention programs in states that choose to legalize recreational marijuana.
Dr. Cerdá and her associates cited several limitations. For example, the use of marijuana was self reported, and the Monitoring the Future results might have missed adolescents who were either absent from school when the survey was taken or had dropped out.
The study was supported by the National Institute on Drug Abuse, the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism, and the New York State Psychiatric Institute. No conflicts of interest were declared.
The legalization of recreational marijuana use is associated with an increase in use of the drug among adolescents, who also perceive it as being less harmful, a new study published online suggests.
In the study, Magdalena Cerdá, DrPH, MPH, and her associates used data from the Monitoring the Future study – a national, annual, cross-sectional survey conducted by the University of Michigan, Ann Arbor, that looks at attitudes about drug use among students in 8th, 10th, and 12th grade. The investigators analyzed the data gathered from 2010 to 2015 in an effort to compare attitudes about marijuana and its use before and after legalization in Washington and Colorado, and in states that did not legalize.
“While the increase in marijuana use among 8th graders in Washington was not significantly greater than zero, the significant decrease in use among 8th graders in states [with no recreational marijuana laws] suggests that if there had been no legalization in Washington, then marijuana use among 8th graders in this state would decrease rather than remain stable, as it did,” wrote Dr. Cerdà of the emergency medicine department at the University of California, Davis, in Sacramento, and her coauthors. “Specifically, the prevalence of regular users of marijuana increased and the prevalence of nonusers decreased; no change was observed among occasional users.”
Legalization, however, did not appear to significantly affect perceived harmfulness or use among 12th graders in any states, nor were there any significant changes after legalization among adolescents in all three grades surveyed in Colorado.
The authors noted that Colorado had a well-developed medical marijuana program in place, with substantial advertising, which might account for the lack of apparent impact of legalization for recreational use.
Commenting on the overall impact of legalization on use, the authors suggested that, besides reducing stigma and perceptions of risk, the legalization of recreational marijuana might have increased availability and potentially decreased the price, which might have led to the increase in use.
Given this, they cautiously proposed increased investment in evidence-based adolescent substance use prevention programs in states that choose to legalize recreational marijuana.
Dr. Cerdá and her associates cited several limitations. For example, the use of marijuana was self reported, and the Monitoring the Future results might have missed adolescents who were either absent from school when the survey was taken or had dropped out.
The study was supported by the National Institute on Drug Abuse, the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism, and the New York State Psychiatric Institute. No conflicts of interest were declared.
Key clinical point: The legalization of recreational marijuana use is associated with an increase in its use among adolescents, who also perceive it as being less harmful.
Major finding: The perceived harmfulness of marijuana declined by 14.2% among 8th graders and 16.1% among 10th graders after legalization in Washington, compared with 4.9% and 7.1% decreases among 8th and 10th graders in states that did not legalize.
Data source: The Monitoring the Future study is a national, annual, cross-sectional survey of 253,902 students in the 8th, 10th, and 12th grades.
Disclosures: The study was supported by the National Institute on Drug Abuse, the National Institutes of Health, the National Institute on Alcohol Abuse and Alcoholism, and the New York State Psychiatric Institute. No conflicts of interest were declared.
Racial disparities not seen in child asthma hospitalizations
A study of racial disparities in the hospitalization outcomes of children with asthma in the Medicaid system has found no significant differences in outcomes such as revisit and readmission rates, a study published online Dec. 26 shows.
Researchers examined the outcomes for 11,079 matched pairs of black and white children from the same state, admitted for asthma during a nearly 2-year period across 33 states. The black and white patients were matched on clinical characteristics (Pediatrics. 2016 Dec 26. doi: 10.1542/peds.2016-1221).
However, the study did find that ICU use was significantly higher among black patients, compared with white patients in four states (22.2% vs. 17.5%, P less than .001). Only 23 deaths were recorded among the 22,158 patients – 12 among black patients and 13 among white; a difference that was not significant.
“Because the number of children in Medicaid continues to increase due to the Affordable Care Act, it will be important to keep monitoring for potential racial disparities in hospitalization treatment styles and patient outcomes,” wrote Dr. Silber, of the Children’s Hospital of Philadelphia, and his coauthors. “Because our study was large, including more than 11,000 pairs of patients, we did see some statistically significant differences between black and white Medicaid patients in ICU use and [length of stay], but in most cases, such differences were small in any economic or clinical sense.”
The authors did note some key limitations of study, including a reliance on retrospective Medicaid claims from billing records – which they said may have led to false positives or negatives – and an absence of data on household smoking status and controller medication compliance, both of which could influence readmission and revisit risk.
Dr. Silber and his coauthors also pointed out that children were matched within the state, not within the hospital. “If black children went to worse hospitals than whites, we may not have seen these outcome differences if whites were matched to blacks always within the same hospital.”
The study was supported by the Agency for Healthcare Research and Quality. No conflicts of interest were declared.
The “most disturbing disparities in asthma care” are tied to the practices that limit or deny both outpatient and community care to pediatric Medicaid patients, wrote Lisa D. Young, MD, and Jay G. Berry, MD, MPH, in an accompanying editorial (Pediatrics 2016 Dec 26. doi: 10.1542/peds.2016-3485). “Although we are pleased that Silber and [his] colleagues’ work reports parity in hospital use for children with asthma by race, it will remain important to shine light on other disparities in children with asthma until those disparities are eliminated.”
Among the reasons that such care is either limited or denied is that in some states, Medicaid payments do not underwrite “the cost of the time and effort intensive health services required to optimize the health of the children. Moreover, some states recurrently threaten or enact reductions in funding for their Medicaid program. These legislative actions undoubtedly deincentivize outpatient pediatric providers to care for children with Medicaid,” they wrote.
Dr. Young is affiliated with the Pediatric Clinic and the East Alabama Medical Center, Auburn; Dr. Berry is with the division of general pediatrics at Boston Children’s Hospital and with Harvard Medical School, Boston. No conflicts of interest were declared.
The “most disturbing disparities in asthma care” are tied to the practices that limit or deny both outpatient and community care to pediatric Medicaid patients, wrote Lisa D. Young, MD, and Jay G. Berry, MD, MPH, in an accompanying editorial (Pediatrics 2016 Dec 26. doi: 10.1542/peds.2016-3485). “Although we are pleased that Silber and [his] colleagues’ work reports parity in hospital use for children with asthma by race, it will remain important to shine light on other disparities in children with asthma until those disparities are eliminated.”
Among the reasons that such care is either limited or denied is that in some states, Medicaid payments do not underwrite “the cost of the time and effort intensive health services required to optimize the health of the children. Moreover, some states recurrently threaten or enact reductions in funding for their Medicaid program. These legislative actions undoubtedly deincentivize outpatient pediatric providers to care for children with Medicaid,” they wrote.
Dr. Young is affiliated with the Pediatric Clinic and the East Alabama Medical Center, Auburn; Dr. Berry is with the division of general pediatrics at Boston Children’s Hospital and with Harvard Medical School, Boston. No conflicts of interest were declared.
The “most disturbing disparities in asthma care” are tied to the practices that limit or deny both outpatient and community care to pediatric Medicaid patients, wrote Lisa D. Young, MD, and Jay G. Berry, MD, MPH, in an accompanying editorial (Pediatrics 2016 Dec 26. doi: 10.1542/peds.2016-3485). “Although we are pleased that Silber and [his] colleagues’ work reports parity in hospital use for children with asthma by race, it will remain important to shine light on other disparities in children with asthma until those disparities are eliminated.”
Among the reasons that such care is either limited or denied is that in some states, Medicaid payments do not underwrite “the cost of the time and effort intensive health services required to optimize the health of the children. Moreover, some states recurrently threaten or enact reductions in funding for their Medicaid program. These legislative actions undoubtedly deincentivize outpatient pediatric providers to care for children with Medicaid,” they wrote.
Dr. Young is affiliated with the Pediatric Clinic and the East Alabama Medical Center, Auburn; Dr. Berry is with the division of general pediatrics at Boston Children’s Hospital and with Harvard Medical School, Boston. No conflicts of interest were declared.
A study of racial disparities in the hospitalization outcomes of children with asthma in the Medicaid system has found no significant differences in outcomes such as revisit and readmission rates, a study published online Dec. 26 shows.
Researchers examined the outcomes for 11,079 matched pairs of black and white children from the same state, admitted for asthma during a nearly 2-year period across 33 states. The black and white patients were matched on clinical characteristics (Pediatrics. 2016 Dec 26. doi: 10.1542/peds.2016-1221).
However, the study did find that ICU use was significantly higher among black patients, compared with white patients in four states (22.2% vs. 17.5%, P less than .001). Only 23 deaths were recorded among the 22,158 patients – 12 among black patients and 13 among white; a difference that was not significant.
“Because the number of children in Medicaid continues to increase due to the Affordable Care Act, it will be important to keep monitoring for potential racial disparities in hospitalization treatment styles and patient outcomes,” wrote Dr. Silber, of the Children’s Hospital of Philadelphia, and his coauthors. “Because our study was large, including more than 11,000 pairs of patients, we did see some statistically significant differences between black and white Medicaid patients in ICU use and [length of stay], but in most cases, such differences were small in any economic or clinical sense.”
The authors did note some key limitations of study, including a reliance on retrospective Medicaid claims from billing records – which they said may have led to false positives or negatives – and an absence of data on household smoking status and controller medication compliance, both of which could influence readmission and revisit risk.
Dr. Silber and his coauthors also pointed out that children were matched within the state, not within the hospital. “If black children went to worse hospitals than whites, we may not have seen these outcome differences if whites were matched to blacks always within the same hospital.”
The study was supported by the Agency for Healthcare Research and Quality. No conflicts of interest were declared.
A study of racial disparities in the hospitalization outcomes of children with asthma in the Medicaid system has found no significant differences in outcomes such as revisit and readmission rates, a study published online Dec. 26 shows.
Researchers examined the outcomes for 11,079 matched pairs of black and white children from the same state, admitted for asthma during a nearly 2-year period across 33 states. The black and white patients were matched on clinical characteristics (Pediatrics. 2016 Dec 26. doi: 10.1542/peds.2016-1221).
However, the study did find that ICU use was significantly higher among black patients, compared with white patients in four states (22.2% vs. 17.5%, P less than .001). Only 23 deaths were recorded among the 22,158 patients – 12 among black patients and 13 among white; a difference that was not significant.
“Because the number of children in Medicaid continues to increase due to the Affordable Care Act, it will be important to keep monitoring for potential racial disparities in hospitalization treatment styles and patient outcomes,” wrote Dr. Silber, of the Children’s Hospital of Philadelphia, and his coauthors. “Because our study was large, including more than 11,000 pairs of patients, we did see some statistically significant differences between black and white Medicaid patients in ICU use and [length of stay], but in most cases, such differences were small in any economic or clinical sense.”
The authors did note some key limitations of study, including a reliance on retrospective Medicaid claims from billing records – which they said may have led to false positives or negatives – and an absence of data on household smoking status and controller medication compliance, both of which could influence readmission and revisit risk.
Dr. Silber and his coauthors also pointed out that children were matched within the state, not within the hospital. “If black children went to worse hospitals than whites, we may not have seen these outcome differences if whites were matched to blacks always within the same hospital.”
The study was supported by the Agency for Healthcare Research and Quality. No conflicts of interest were declared.
Key clinical point: No significant differences in revisit or readmission rates were found between black and white children admitted to hospital for asthma.
Major finding: Black and white children hospitalized for asthma across 33 states show no significant differences in revisit or readmission rates or length of stay.
Data source: Retrospective matched cohort study in 11,079 matched pairs of black and white children from within same state.
Disclosures: The study was supported by the Agency for Healthcare Research and Quality. No conflicts of interest were declared.
ACOG supports delayed umbilical cord clamping for term infants
The American College of Obstetricians and Gynecologists recommends that umbilical cord clamping be delayed for at least 30-60 seconds after birth in vigorous preterm and term infants.
Since early studies suggested that up to 90% of the blood transfer from the placenta to the newborn after birth happens with an infant’s first few breaths, it has become common practice to clamp the cord within 15-20 seconds after birth.
In 2012, the ACOG Committee on Obstetric Practice recommended use of delayed umbilical cord clamping in preterm infants, but found a lack of evidence in term infants. “However, more recent randomized controlled trials of term and preterm infants as well as physiologic studies of blood volume, oxygenation, and arterial pressure have evaluated the effects of immediate versus delayed umbilical cord clamping (usually defined as cord clamping at least 30-60 seconds after birth),” wrote the members of the College’s Committee on Obstetric Practice in an updated opinion released on Dec. 21.
These studies showed that around 80 mL of blood is transferred from the placenta within 1 minute of birth, which appears to be facilitated by the newborn’s initial breaths. This initial transfer of blood supplies significant quantities of iron – 40-50 mg/kg of body weight - and is associated with a lower risk of iron deficiency during the first year of life (Obstet Gynecol. 2017;129:e5-10).
The committee cited a 2012 systematic review of the data on preterm infants that found a 39% reduction in the number of infants requiring transfusion for anemia when delayed umbilical cord clamping – defined as a delay of 30-180 seconds – was used, compared with immediate clamping. The review also noted a 41% reduction in the incidence of intraventricular hemorrhage and 38% reduction in necrotizing enterocolitis, compared with immediate umbilical cord clamping.
Similarly in term infants, those who had their umbilical cord clamped early showed significantly lower hemoglobin concentrations at birth and were more likely to have iron deficiency at 3-6 months of age, compared with term infants who had delayed clamping.
The committee did note that preterm infants who experienced delayed cord clamping showed higher peak bilirubin levels, compared with early clamping. In term infants, delayed cord clamping was associated with a small increase in the incidence of jaundice requiring phototherapy, although there were no significant differences in the rates of polycythemia or jaundice overall.
“Consequently, obstetrician-gynecologists and other obstetric care providers adopting delayed cord clamping in term infants should ensure that mechanisms are in place to monitor for and treat neonatal jaundice,” the committee members wrote.
With regards to maternal outcomes, there had been concerns that delayed umbilical cord clamping could increase the risk of maternal hemorrhage. But a review of five trials including more than 2,200 women found no sign of an increase in adverse events such as postpartum hemorrhage, increased blood loss at delivery, blood transfusions, or reduced postpartum hemoglobin levels.
“However, when there is increased risk of hemorrhage (e.g., placenta previa or placental abruption), the benefits of delayed umbilical cord clamping need to be balanced with the need for timely hemodynamic stabilization of the woman,” the authors wrote.
The committee found that skin-to-skin care could still take place with delayed umbilical cord clamping, as gravity was not necessary to facilitate the flow of blood from the placenta to the newborn. They also advised that early care of the newborn could still be carried out, including drying and stimulating for the first breath.
Delayed umbilical cord clamping should also not interfere with active management of the third stage of labor, including the use of uterotonic agents after delivery.
The authors reported having no conflicts of interest.
The American College of Obstetricians and Gynecologists recommends that umbilical cord clamping be delayed for at least 30-60 seconds after birth in vigorous preterm and term infants.
Since early studies suggested that up to 90% of the blood transfer from the placenta to the newborn after birth happens with an infant’s first few breaths, it has become common practice to clamp the cord within 15-20 seconds after birth.
In 2012, the ACOG Committee on Obstetric Practice recommended use of delayed umbilical cord clamping in preterm infants, but found a lack of evidence in term infants. “However, more recent randomized controlled trials of term and preterm infants as well as physiologic studies of blood volume, oxygenation, and arterial pressure have evaluated the effects of immediate versus delayed umbilical cord clamping (usually defined as cord clamping at least 30-60 seconds after birth),” wrote the members of the College’s Committee on Obstetric Practice in an updated opinion released on Dec. 21.
These studies showed that around 80 mL of blood is transferred from the placenta within 1 minute of birth, which appears to be facilitated by the newborn’s initial breaths. This initial transfer of blood supplies significant quantities of iron – 40-50 mg/kg of body weight - and is associated with a lower risk of iron deficiency during the first year of life (Obstet Gynecol. 2017;129:e5-10).
The committee cited a 2012 systematic review of the data on preterm infants that found a 39% reduction in the number of infants requiring transfusion for anemia when delayed umbilical cord clamping – defined as a delay of 30-180 seconds – was used, compared with immediate clamping. The review also noted a 41% reduction in the incidence of intraventricular hemorrhage and 38% reduction in necrotizing enterocolitis, compared with immediate umbilical cord clamping.
Similarly in term infants, those who had their umbilical cord clamped early showed significantly lower hemoglobin concentrations at birth and were more likely to have iron deficiency at 3-6 months of age, compared with term infants who had delayed clamping.
The committee did note that preterm infants who experienced delayed cord clamping showed higher peak bilirubin levels, compared with early clamping. In term infants, delayed cord clamping was associated with a small increase in the incidence of jaundice requiring phototherapy, although there were no significant differences in the rates of polycythemia or jaundice overall.
“Consequently, obstetrician-gynecologists and other obstetric care providers adopting delayed cord clamping in term infants should ensure that mechanisms are in place to monitor for and treat neonatal jaundice,” the committee members wrote.
With regards to maternal outcomes, there had been concerns that delayed umbilical cord clamping could increase the risk of maternal hemorrhage. But a review of five trials including more than 2,200 women found no sign of an increase in adverse events such as postpartum hemorrhage, increased blood loss at delivery, blood transfusions, or reduced postpartum hemoglobin levels.
“However, when there is increased risk of hemorrhage (e.g., placenta previa or placental abruption), the benefits of delayed umbilical cord clamping need to be balanced with the need for timely hemodynamic stabilization of the woman,” the authors wrote.
The committee found that skin-to-skin care could still take place with delayed umbilical cord clamping, as gravity was not necessary to facilitate the flow of blood from the placenta to the newborn. They also advised that early care of the newborn could still be carried out, including drying and stimulating for the first breath.
Delayed umbilical cord clamping should also not interfere with active management of the third stage of labor, including the use of uterotonic agents after delivery.
The authors reported having no conflicts of interest.
The American College of Obstetricians and Gynecologists recommends that umbilical cord clamping be delayed for at least 30-60 seconds after birth in vigorous preterm and term infants.
Since early studies suggested that up to 90% of the blood transfer from the placenta to the newborn after birth happens with an infant’s first few breaths, it has become common practice to clamp the cord within 15-20 seconds after birth.
In 2012, the ACOG Committee on Obstetric Practice recommended use of delayed umbilical cord clamping in preterm infants, but found a lack of evidence in term infants. “However, more recent randomized controlled trials of term and preterm infants as well as physiologic studies of blood volume, oxygenation, and arterial pressure have evaluated the effects of immediate versus delayed umbilical cord clamping (usually defined as cord clamping at least 30-60 seconds after birth),” wrote the members of the College’s Committee on Obstetric Practice in an updated opinion released on Dec. 21.
These studies showed that around 80 mL of blood is transferred from the placenta within 1 minute of birth, which appears to be facilitated by the newborn’s initial breaths. This initial transfer of blood supplies significant quantities of iron – 40-50 mg/kg of body weight - and is associated with a lower risk of iron deficiency during the first year of life (Obstet Gynecol. 2017;129:e5-10).
The committee cited a 2012 systematic review of the data on preterm infants that found a 39% reduction in the number of infants requiring transfusion for anemia when delayed umbilical cord clamping – defined as a delay of 30-180 seconds – was used, compared with immediate clamping. The review also noted a 41% reduction in the incidence of intraventricular hemorrhage and 38% reduction in necrotizing enterocolitis, compared with immediate umbilical cord clamping.
Similarly in term infants, those who had their umbilical cord clamped early showed significantly lower hemoglobin concentrations at birth and were more likely to have iron deficiency at 3-6 months of age, compared with term infants who had delayed clamping.
The committee did note that preterm infants who experienced delayed cord clamping showed higher peak bilirubin levels, compared with early clamping. In term infants, delayed cord clamping was associated with a small increase in the incidence of jaundice requiring phototherapy, although there were no significant differences in the rates of polycythemia or jaundice overall.
“Consequently, obstetrician-gynecologists and other obstetric care providers adopting delayed cord clamping in term infants should ensure that mechanisms are in place to monitor for and treat neonatal jaundice,” the committee members wrote.
With regards to maternal outcomes, there had been concerns that delayed umbilical cord clamping could increase the risk of maternal hemorrhage. But a review of five trials including more than 2,200 women found no sign of an increase in adverse events such as postpartum hemorrhage, increased blood loss at delivery, blood transfusions, or reduced postpartum hemoglobin levels.
“However, when there is increased risk of hemorrhage (e.g., placenta previa or placental abruption), the benefits of delayed umbilical cord clamping need to be balanced with the need for timely hemodynamic stabilization of the woman,” the authors wrote.
The committee found that skin-to-skin care could still take place with delayed umbilical cord clamping, as gravity was not necessary to facilitate the flow of blood from the placenta to the newborn. They also advised that early care of the newborn could still be carried out, including drying and stimulating for the first breath.
Delayed umbilical cord clamping should also not interfere with active management of the third stage of labor, including the use of uterotonic agents after delivery.
The authors reported having no conflicts of interest.
Shorter-course antimicrobials do not reduce antimicrobial resistance in AOM
A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure and higher symptom scores but without any associated reduction in the rates of antimicrobial resistance or adverse events.
Alejandro Hoberman, MD, of the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center, and his coauthors report the results of a study in which 520 children aged 6-23 months were randomized to either 10 days of amoxicillin-clavulanate therapy, or 5 days of therapy followed by 5 days of placebo.
The children who received the full 10-day course also had lower mean symptom scores in the 6-14 days after initiation of therapy, compared with those who received 5 days of treatment (1.34 vs. 1.61; P = 0.07), while the number of children whose symptom scores decreased by 50% from baseline to the end of treatment was significantly lower in the 5-day group.
However, there were no significant differences between the two groups in the rate of nasopharyngeal colonization pathogens not susceptible to penicillin: 47% in the 10-day group, compared with 44% in the 5-day group (N Engl J Med. 2016 Dec 22;375[25]:2446-56).
Similarly, the rates of recurrence and adverse events were not significantly different between the two groups.
A shorter duration of treatment has been considered as a strategy for reducing the risk of antimicrobial resistance, but clinical trials so far have showed either modest difference favoring the standard duration of treatment, or no difference at all.
“The outcome differences we found were larger than the differences that have been reported previously, mainly because the rates of clinical failure among children who received reduced duration treatment were higher in our trial than in previous trials,” Dr. Hoberman and his associates wrote.
The researchers did note that clinical failure rates were higher among children with greater exposure to other children, and those with infection in both ears rather than a single ear.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.
The study of acute otitis media is challenging owing to antibiotic pharmacokinetics, age of the patients, variation in regional pathogens, polymicrobial infection, viral cofactors, antibiotic resistance, status of patients with regard to receipt of PCV7 or PCV13, and a high rate of spontaneous resolution.
The study was not designed to address outcomes in older children, children with less severe acute otitis media or with acute otitis media in one ear, or children with additional risk factors such as cleft palate or trisomy 21. In addition, there is a paucity of studies from resource-poor and low income countries.
But for now, 10 days of amoxicillin-clavulanate for children younger than 2 years of age who have a definite diagnosis of acute otitis media seems to be a reasonable option.
Margaret A. Kenna, MD, MPH, is from the department of otolaryngology and communication enhancement at the Boston Children’s Hospital. These comments are excerpted from an accompanying editorial (N Engl J Med. 2016 Dec 22;375[25]:2492-93). Dr. Kenna declared a grant from Agilis outside the submitted work.
The study of acute otitis media is challenging owing to antibiotic pharmacokinetics, age of the patients, variation in regional pathogens, polymicrobial infection, viral cofactors, antibiotic resistance, status of patients with regard to receipt of PCV7 or PCV13, and a high rate of spontaneous resolution.
The study was not designed to address outcomes in older children, children with less severe acute otitis media or with acute otitis media in one ear, or children with additional risk factors such as cleft palate or trisomy 21. In addition, there is a paucity of studies from resource-poor and low income countries.
But for now, 10 days of amoxicillin-clavulanate for children younger than 2 years of age who have a definite diagnosis of acute otitis media seems to be a reasonable option.
Margaret A. Kenna, MD, MPH, is from the department of otolaryngology and communication enhancement at the Boston Children’s Hospital. These comments are excerpted from an accompanying editorial (N Engl J Med. 2016 Dec 22;375[25]:2492-93). Dr. Kenna declared a grant from Agilis outside the submitted work.
The study of acute otitis media is challenging owing to antibiotic pharmacokinetics, age of the patients, variation in regional pathogens, polymicrobial infection, viral cofactors, antibiotic resistance, status of patients with regard to receipt of PCV7 or PCV13, and a high rate of spontaneous resolution.
The study was not designed to address outcomes in older children, children with less severe acute otitis media or with acute otitis media in one ear, or children with additional risk factors such as cleft palate or trisomy 21. In addition, there is a paucity of studies from resource-poor and low income countries.
But for now, 10 days of amoxicillin-clavulanate for children younger than 2 years of age who have a definite diagnosis of acute otitis media seems to be a reasonable option.
Margaret A. Kenna, MD, MPH, is from the department of otolaryngology and communication enhancement at the Boston Children’s Hospital. These comments are excerpted from an accompanying editorial (N Engl J Med. 2016 Dec 22;375[25]:2492-93). Dr. Kenna declared a grant from Agilis outside the submitted work.
A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure and higher symptom scores but without any associated reduction in the rates of antimicrobial resistance or adverse events.
Alejandro Hoberman, MD, of the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center, and his coauthors report the results of a study in which 520 children aged 6-23 months were randomized to either 10 days of amoxicillin-clavulanate therapy, or 5 days of therapy followed by 5 days of placebo.
The children who received the full 10-day course also had lower mean symptom scores in the 6-14 days after initiation of therapy, compared with those who received 5 days of treatment (1.34 vs. 1.61; P = 0.07), while the number of children whose symptom scores decreased by 50% from baseline to the end of treatment was significantly lower in the 5-day group.
However, there were no significant differences between the two groups in the rate of nasopharyngeal colonization pathogens not susceptible to penicillin: 47% in the 10-day group, compared with 44% in the 5-day group (N Engl J Med. 2016 Dec 22;375[25]:2446-56).
Similarly, the rates of recurrence and adverse events were not significantly different between the two groups.
A shorter duration of treatment has been considered as a strategy for reducing the risk of antimicrobial resistance, but clinical trials so far have showed either modest difference favoring the standard duration of treatment, or no difference at all.
“The outcome differences we found were larger than the differences that have been reported previously, mainly because the rates of clinical failure among children who received reduced duration treatment were higher in our trial than in previous trials,” Dr. Hoberman and his associates wrote.
The researchers did note that clinical failure rates were higher among children with greater exposure to other children, and those with infection in both ears rather than a single ear.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.
A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure and higher symptom scores but without any associated reduction in the rates of antimicrobial resistance or adverse events.
Alejandro Hoberman, MD, of the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center, and his coauthors report the results of a study in which 520 children aged 6-23 months were randomized to either 10 days of amoxicillin-clavulanate therapy, or 5 days of therapy followed by 5 days of placebo.
The children who received the full 10-day course also had lower mean symptom scores in the 6-14 days after initiation of therapy, compared with those who received 5 days of treatment (1.34 vs. 1.61; P = 0.07), while the number of children whose symptom scores decreased by 50% from baseline to the end of treatment was significantly lower in the 5-day group.
However, there were no significant differences between the two groups in the rate of nasopharyngeal colonization pathogens not susceptible to penicillin: 47% in the 10-day group, compared with 44% in the 5-day group (N Engl J Med. 2016 Dec 22;375[25]:2446-56).
Similarly, the rates of recurrence and adverse events were not significantly different between the two groups.
A shorter duration of treatment has been considered as a strategy for reducing the risk of antimicrobial resistance, but clinical trials so far have showed either modest difference favoring the standard duration of treatment, or no difference at all.
“The outcome differences we found were larger than the differences that have been reported previously, mainly because the rates of clinical failure among children who received reduced duration treatment were higher in our trial than in previous trials,” Dr. Hoberman and his associates wrote.
The researchers did note that clinical failure rates were higher among children with greater exposure to other children, and those with infection in both ears rather than a single ear.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: A shorter duration of antimicrobial therapy for acute otitis media (AOM) in children is associated with higher rates of clinical failure without a reduction in the rates of antimicrobial resistance.
Major finding: Children who received 5 days of antimicrobial experienced clinical failure rates of 35%, compared with 16% in those who received a full 10-day course.
Data source: Randomized controlled trial in 520 children aged 6-23 months with AOM.
Disclosures: The study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health. Dr. Hoberman and Dr. Judith M. Martin declared consulting fees from Genocea Biosciences, and Dr. Hoberman declared grant support from Ricoh Innovations and holding pending patents for a reduced clavulanate concentration version of amoxicillin–clavulanate potassium, and a method and device for aiding in the diagnosis of otitis media. No other conflicts of interest were declared.
Replicative Zika RNA found in brain and placental tissue
U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.
In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.
“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.
Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.
There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.
Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).
Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).
There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.
All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.
Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.
Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.
“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.
Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.
“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”
No conflicts of interest were declared.
[email protected]
On Twitter @idpractitioner
U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.
In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.
“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.
Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.
There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.
Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).
Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).
There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.
All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.
Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.
Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.
“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.
Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.
“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”
No conflicts of interest were declared.
[email protected]
On Twitter @idpractitioner
U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.
In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.
“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.
Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.
There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.
Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).
Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).
There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.
All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.
Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.
Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.
“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.
Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.
“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”
No conflicts of interest were declared.
[email protected]
On Twitter @idpractitioner
FROM EMERGING INFECTIOUS DISEASES
Key clinical point: Researchers isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placental tissues of women suspected of being infected with Zika virus during pregnancy.
Major finding: Among women who had an adverse pregnancy or birth outcome, 75% tested positive for Zika virus via RT-PCR, compared to 36% of women with live-born healthy infants.
Data source: Case series of 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy.
Disclosures: No conflicts of interest were declared.