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EHR woes will get worse before they get better: ONC chief
WASHINGTON – EHR woes may tick up as medical practices begin to move from fee for service to a value-based care model, according to the new federal health IT leader, B. Vindell Washington, MD.
“If you are in an environment where you have, say for example, 20%-25% of your patients that are in an accountable care model and the rest of your entire panel is a fee-for-service model, then you’re really not in a position to really reap the full benefit, and quite frankly you are straddling the fence in terms of both your work flow and patient delivery,” Dr. Washington, National Coordinator for Health Information Technology, said at a Sept. 19 press briefing. That said, “I think that there will be improvements for physicians as we work our way through delivery system reform.”
The Office of the National Coordinator for Health Information Technology (ONC) is working on regulations that would push EHR vendors to publish app interfaces to foster innovation, create more efficient work-flow applications, and improve EHRs in general, said Dr. Washington, former president and chief medical information officer of the Franciscan Missionaries of Our Lady Health System Medical Group, Baton Rogue, La. “This change is not just a change in the tool that folks are using, it is also a change in the system in which they operate.”
Interoperability also should improve as more clinicians move into value-based care models, he said. For example, in Tulsa, Okla., three competing health systems are participating in the Comprehensive Primary Care Initiative demonstration. The health systems involved in the demonstration are seeing unprecedented levels of information sharing between them because participation in CPC requires it.
“Part of this value proposition comes when you take care of groups of patients and you move into more of the CPC+ or medical home or coordinated care models where the sort of larger, longer view and team-based approach to care become more and more prominent,” Dr. Washington said.
He also talked about the value of documenting efforts related to process measures, and the criticism that clinicians are simply checking boxes rather than focusing on outcomes.
Dr. Washington acknowledged that defining and measuring outcomes is a much more difficult task. He noted that improvement in health is the goal. And while the measure may be difficult, what physicians “need to do in health care to lead to those outcomes, to have people have better, healthier, more enriched lives, you end up with measures around.”
As an example, he pointed to preventing diabetic retinopathy or amputation. “Our best guess at how to do that is to keep their hemoglobin A1c in a certain range,” he said, adding that while tracking hemoglobin A1c is the measurement, “what you really want is the [diabetes patient] to have a long life, keep their eyesight, and not lose a limb. It’s that juxtaposition of what you can measure easily versus what the ultimate outcome” is, and physicians will come up with a series of steps in order to achieve the outcome of improved overall health status.
WASHINGTON – EHR woes may tick up as medical practices begin to move from fee for service to a value-based care model, according to the new federal health IT leader, B. Vindell Washington, MD.
“If you are in an environment where you have, say for example, 20%-25% of your patients that are in an accountable care model and the rest of your entire panel is a fee-for-service model, then you’re really not in a position to really reap the full benefit, and quite frankly you are straddling the fence in terms of both your work flow and patient delivery,” Dr. Washington, National Coordinator for Health Information Technology, said at a Sept. 19 press briefing. That said, “I think that there will be improvements for physicians as we work our way through delivery system reform.”
The Office of the National Coordinator for Health Information Technology (ONC) is working on regulations that would push EHR vendors to publish app interfaces to foster innovation, create more efficient work-flow applications, and improve EHRs in general, said Dr. Washington, former president and chief medical information officer of the Franciscan Missionaries of Our Lady Health System Medical Group, Baton Rogue, La. “This change is not just a change in the tool that folks are using, it is also a change in the system in which they operate.”
Interoperability also should improve as more clinicians move into value-based care models, he said. For example, in Tulsa, Okla., three competing health systems are participating in the Comprehensive Primary Care Initiative demonstration. The health systems involved in the demonstration are seeing unprecedented levels of information sharing between them because participation in CPC requires it.
“Part of this value proposition comes when you take care of groups of patients and you move into more of the CPC+ or medical home or coordinated care models where the sort of larger, longer view and team-based approach to care become more and more prominent,” Dr. Washington said.
He also talked about the value of documenting efforts related to process measures, and the criticism that clinicians are simply checking boxes rather than focusing on outcomes.
Dr. Washington acknowledged that defining and measuring outcomes is a much more difficult task. He noted that improvement in health is the goal. And while the measure may be difficult, what physicians “need to do in health care to lead to those outcomes, to have people have better, healthier, more enriched lives, you end up with measures around.”
As an example, he pointed to preventing diabetic retinopathy or amputation. “Our best guess at how to do that is to keep their hemoglobin A1c in a certain range,” he said, adding that while tracking hemoglobin A1c is the measurement, “what you really want is the [diabetes patient] to have a long life, keep their eyesight, and not lose a limb. It’s that juxtaposition of what you can measure easily versus what the ultimate outcome” is, and physicians will come up with a series of steps in order to achieve the outcome of improved overall health status.
WASHINGTON – EHR woes may tick up as medical practices begin to move from fee for service to a value-based care model, according to the new federal health IT leader, B. Vindell Washington, MD.
“If you are in an environment where you have, say for example, 20%-25% of your patients that are in an accountable care model and the rest of your entire panel is a fee-for-service model, then you’re really not in a position to really reap the full benefit, and quite frankly you are straddling the fence in terms of both your work flow and patient delivery,” Dr. Washington, National Coordinator for Health Information Technology, said at a Sept. 19 press briefing. That said, “I think that there will be improvements for physicians as we work our way through delivery system reform.”
The Office of the National Coordinator for Health Information Technology (ONC) is working on regulations that would push EHR vendors to publish app interfaces to foster innovation, create more efficient work-flow applications, and improve EHRs in general, said Dr. Washington, former president and chief medical information officer of the Franciscan Missionaries of Our Lady Health System Medical Group, Baton Rogue, La. “This change is not just a change in the tool that folks are using, it is also a change in the system in which they operate.”
Interoperability also should improve as more clinicians move into value-based care models, he said. For example, in Tulsa, Okla., three competing health systems are participating in the Comprehensive Primary Care Initiative demonstration. The health systems involved in the demonstration are seeing unprecedented levels of information sharing between them because participation in CPC requires it.
“Part of this value proposition comes when you take care of groups of patients and you move into more of the CPC+ or medical home or coordinated care models where the sort of larger, longer view and team-based approach to care become more and more prominent,” Dr. Washington said.
He also talked about the value of documenting efforts related to process measures, and the criticism that clinicians are simply checking boxes rather than focusing on outcomes.
Dr. Washington acknowledged that defining and measuring outcomes is a much more difficult task. He noted that improvement in health is the goal. And while the measure may be difficult, what physicians “need to do in health care to lead to those outcomes, to have people have better, healthier, more enriched lives, you end up with measures around.”
As an example, he pointed to preventing diabetic retinopathy or amputation. “Our best guess at how to do that is to keep their hemoglobin A1c in a certain range,” he said, adding that while tracking hemoglobin A1c is the measurement, “what you really want is the [diabetes patient] to have a long life, keep their eyesight, and not lose a limb. It’s that juxtaposition of what you can measure easily versus what the ultimate outcome” is, and physicians will come up with a series of steps in order to achieve the outcome of improved overall health status.
More TOPCAT flaws back spironolactone’s HFpEF efficacy
ORLANDO – Spironolactone inched a little closer toward becoming the first and only agent with proven efficacy for treating patients with heart failure with preserved ejection fraction based on further evidence for the drug’s efficacy in a subgroup of patients enrolled in the TOPCAT trial.
In 2014, the initial TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) report showed that spironolactone treatment of patients with heart failure with preserved ejection fraction (HFpEF) for 3 years produced a small, 11% relative reduction in the primary risk endpoint, compared with placebo that was not statistically significant (N Engl J Med. 2014 Apr 10;370[15]:1383-92).
But a follow-up post hoc analysis a year later showed evidence that the roughly half of patients in TOPCAT enrolled at centers in Russia and the Republic of Georgia may not have had HFpEF and also may not have received the planned dosage of spironolactone (Circulation. 2015 Jan 6;131[1]:34-42). An analysis that focused only on the 1,767 HFpEF patients (51% of the total TOPCAT cohort) enrolled in the Americas (United States, Canada, Argentina, and Brazil) showed that, compared with placebo, treatment with spironolactone cut the combined rate of cardiovascular death, nonfatal cardiac arrest, and heart failure hospitalization by 4.5 percentage points, an 18% relative risk reduction that was statistically significant. In the Americas, spironolactone also cut cardiovascular death alone by a relative 26%, and reduced heart failure hospitalization by a relative 18%, both statistically significant.
Additional analysis reported at the annual scientific meeting of the Heart Failure Society of America further supported the idea that many TOPCAT patients enrolled in Russia did not receive a physiologically meaningful dosage of spironolactone. Among 66 Russian patients randomized to the spironolactone arm who reported taking their drug as prescribed and who participated in a random draw of blood specimens 1 year into the study, 20 (30%) failed to show detectable blood levels of canrenone, a characteristic spironolactone metabolite, reported Eileen O’Meara, MD, at the meeting. In contrast, 2 (3%) of 76 enrolled U.S. patients failed to show detectable blood levels of the canrenone metabolite, a 10-fold difference said Dr. O’Meara, a cardiologist at the Montreal Heart Institute.The tested U.S. patients also showed a clear dose-response relationship between their reported spironolactone dosage and their canrenone levels, something not seen in the Russian patients. These new findings, plus the evidence cited in the 2015 analysis, create a compelling case that “actual use of spironolactone in Russia was lower than reported” by the trial participants in Russia and probably in Georgia as well, Dr. O’Meara said. The implication is that spironolactone’s real impact on HFpEF patients is best represented in the 51% of TOPCAT patients from the Americas, she added.
“We believe these findings emphasize the reliability of the Americas data,” said Marc A. Pfeffer, MD, a coinvestigator for TOPCAT and lead author of the 2015 post hoc analysis. “Until someone comes up with a better treatment for patients with HFpEF, we should pay attention to this. People need to get this message. And spironolactone costs 7 cents a day,” said Dr. Pfeffer, professor of medicine at Harvard Medical School in Boston.Currently, no agent is considered proven effective for improving outcomes in HFpEF patients. The 2016 guidelinesfor heart failure treatment from the European Society of Cardiology said “no treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF.”
After the TOPCAT results and post hoc analysis came out in 2014 and 2015 and word spread of spironolactone’s apparent efficacy in the American half of the trial, use of spironolactone to treat HFpEF patient has increased, commented Margaret M. Redfield, MD, a heart failure physician and professor at the Mayo Clinic in Rochester, Minn. She said she often prescribes spironolactone patients to HFpEF patients who require potassium supplementation, generally because of their diuretic treatment. These are the “safest” HFpEF patients for spironolactone treatment, she said, because they face the lowest risk for hyperkalemia, the major adverse effect from spironolactone.
On Twitter @mitchelzoler
This is extraordinarily important information from an extraordinarily important study. I’m strongly persuaded that the data from the Americas in TOPCAT show that spironolactone worked. The new data presented on canrenone levels make me even more ready to exclude from consideration the TOPCAT data from Russia and Georgia.
 |
| Mitchel L. Zoler/Frontline Medical News Dr. Barry H. Greenberg |
The heart failure community is left to decide what conclusions to draw from TOPCAT. I think guideline committees will struggle over what to make of the TOPCAT evidence. Any recommendation in favor of spironolactone needs to be somewhat guarded, but if a group made recommendations in support of spironolactone it would add an impetus for using it.
There has been long-standing interest in treating patients with heart failure with preserved ejection fraction with spironolactone. Currently, about a quarter of these patients take spironolactone. I’m not sure this level of use will increase dramatically because of what we now know about TOPCAT.
Dr. Barry H. Greenberg is professor of medicine and director of the advanced heart failure treatment program at the University of California, San Diego. He had no relevant disclosures. He made these comments in an interview.
This is extraordinarily important information from an extraordinarily important study. I’m strongly persuaded that the data from the Americas in TOPCAT show that spironolactone worked. The new data presented on canrenone levels make me even more ready to exclude from consideration the TOPCAT data from Russia and Georgia.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Barry H. Greenberg |
The heart failure community is left to decide what conclusions to draw from TOPCAT. I think guideline committees will struggle over what to make of the TOPCAT evidence. Any recommendation in favor of spironolactone needs to be somewhat guarded, but if a group made recommendations in support of spironolactone it would add an impetus for using it.
There has been long-standing interest in treating patients with heart failure with preserved ejection fraction with spironolactone. Currently, about a quarter of these patients take spironolactone. I’m not sure this level of use will increase dramatically because of what we now know about TOPCAT.
Dr. Barry H. Greenberg is professor of medicine and director of the advanced heart failure treatment program at the University of California, San Diego. He had no relevant disclosures. He made these comments in an interview.
This is extraordinarily important information from an extraordinarily important study. I’m strongly persuaded that the data from the Americas in TOPCAT show that spironolactone worked. The new data presented on canrenone levels make me even more ready to exclude from consideration the TOPCAT data from Russia and Georgia.
|
| Mitchel L. Zoler/Frontline Medical News Dr. Barry H. Greenberg |
The heart failure community is left to decide what conclusions to draw from TOPCAT. I think guideline committees will struggle over what to make of the TOPCAT evidence. Any recommendation in favor of spironolactone needs to be somewhat guarded, but if a group made recommendations in support of spironolactone it would add an impetus for using it.
There has been long-standing interest in treating patients with heart failure with preserved ejection fraction with spironolactone. Currently, about a quarter of these patients take spironolactone. I’m not sure this level of use will increase dramatically because of what we now know about TOPCAT.
Dr. Barry H. Greenberg is professor of medicine and director of the advanced heart failure treatment program at the University of California, San Diego. He had no relevant disclosures. He made these comments in an interview.
ORLANDO – Spironolactone inched a little closer toward becoming the first and only agent with proven efficacy for treating patients with heart failure with preserved ejection fraction based on further evidence for the drug’s efficacy in a subgroup of patients enrolled in the TOPCAT trial.
In 2014, the initial TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) report showed that spironolactone treatment of patients with heart failure with preserved ejection fraction (HFpEF) for 3 years produced a small, 11% relative reduction in the primary risk endpoint, compared with placebo that was not statistically significant (N Engl J Med. 2014 Apr 10;370[15]:1383-92).
But a follow-up post hoc analysis a year later showed evidence that the roughly half of patients in TOPCAT enrolled at centers in Russia and the Republic of Georgia may not have had HFpEF and also may not have received the planned dosage of spironolactone (Circulation. 2015 Jan 6;131[1]:34-42). An analysis that focused only on the 1,767 HFpEF patients (51% of the total TOPCAT cohort) enrolled in the Americas (United States, Canada, Argentina, and Brazil) showed that, compared with placebo, treatment with spironolactone cut the combined rate of cardiovascular death, nonfatal cardiac arrest, and heart failure hospitalization by 4.5 percentage points, an 18% relative risk reduction that was statistically significant. In the Americas, spironolactone also cut cardiovascular death alone by a relative 26%, and reduced heart failure hospitalization by a relative 18%, both statistically significant.
Additional analysis reported at the annual scientific meeting of the Heart Failure Society of America further supported the idea that many TOPCAT patients enrolled in Russia did not receive a physiologically meaningful dosage of spironolactone. Among 66 Russian patients randomized to the spironolactone arm who reported taking their drug as prescribed and who participated in a random draw of blood specimens 1 year into the study, 20 (30%) failed to show detectable blood levels of canrenone, a characteristic spironolactone metabolite, reported Eileen O’Meara, MD, at the meeting. In contrast, 2 (3%) of 76 enrolled U.S. patients failed to show detectable blood levels of the canrenone metabolite, a 10-fold difference said Dr. O’Meara, a cardiologist at the Montreal Heart Institute.The tested U.S. patients also showed a clear dose-response relationship between their reported spironolactone dosage and their canrenone levels, something not seen in the Russian patients. These new findings, plus the evidence cited in the 2015 analysis, create a compelling case that “actual use of spironolactone in Russia was lower than reported” by the trial participants in Russia and probably in Georgia as well, Dr. O’Meara said. The implication is that spironolactone’s real impact on HFpEF patients is best represented in the 51% of TOPCAT patients from the Americas, she added.
“We believe these findings emphasize the reliability of the Americas data,” said Marc A. Pfeffer, MD, a coinvestigator for TOPCAT and lead author of the 2015 post hoc analysis. “Until someone comes up with a better treatment for patients with HFpEF, we should pay attention to this. People need to get this message. And spironolactone costs 7 cents a day,” said Dr. Pfeffer, professor of medicine at Harvard Medical School in Boston.Currently, no agent is considered proven effective for improving outcomes in HFpEF patients. The 2016 guidelinesfor heart failure treatment from the European Society of Cardiology said “no treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF.”
After the TOPCAT results and post hoc analysis came out in 2014 and 2015 and word spread of spironolactone’s apparent efficacy in the American half of the trial, use of spironolactone to treat HFpEF patient has increased, commented Margaret M. Redfield, MD, a heart failure physician and professor at the Mayo Clinic in Rochester, Minn. She said she often prescribes spironolactone patients to HFpEF patients who require potassium supplementation, generally because of their diuretic treatment. These are the “safest” HFpEF patients for spironolactone treatment, she said, because they face the lowest risk for hyperkalemia, the major adverse effect from spironolactone.
On Twitter @mitchelzoler
ORLANDO – Spironolactone inched a little closer toward becoming the first and only agent with proven efficacy for treating patients with heart failure with preserved ejection fraction based on further evidence for the drug’s efficacy in a subgroup of patients enrolled in the TOPCAT trial.
In 2014, the initial TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) report showed that spironolactone treatment of patients with heart failure with preserved ejection fraction (HFpEF) for 3 years produced a small, 11% relative reduction in the primary risk endpoint, compared with placebo that was not statistically significant (N Engl J Med. 2014 Apr 10;370[15]:1383-92).
But a follow-up post hoc analysis a year later showed evidence that the roughly half of patients in TOPCAT enrolled at centers in Russia and the Republic of Georgia may not have had HFpEF and also may not have received the planned dosage of spironolactone (Circulation. 2015 Jan 6;131[1]:34-42). An analysis that focused only on the 1,767 HFpEF patients (51% of the total TOPCAT cohort) enrolled in the Americas (United States, Canada, Argentina, and Brazil) showed that, compared with placebo, treatment with spironolactone cut the combined rate of cardiovascular death, nonfatal cardiac arrest, and heart failure hospitalization by 4.5 percentage points, an 18% relative risk reduction that was statistically significant. In the Americas, spironolactone also cut cardiovascular death alone by a relative 26%, and reduced heart failure hospitalization by a relative 18%, both statistically significant.
Additional analysis reported at the annual scientific meeting of the Heart Failure Society of America further supported the idea that many TOPCAT patients enrolled in Russia did not receive a physiologically meaningful dosage of spironolactone. Among 66 Russian patients randomized to the spironolactone arm who reported taking their drug as prescribed and who participated in a random draw of blood specimens 1 year into the study, 20 (30%) failed to show detectable blood levels of canrenone, a characteristic spironolactone metabolite, reported Eileen O’Meara, MD, at the meeting. In contrast, 2 (3%) of 76 enrolled U.S. patients failed to show detectable blood levels of the canrenone metabolite, a 10-fold difference said Dr. O’Meara, a cardiologist at the Montreal Heart Institute.The tested U.S. patients also showed a clear dose-response relationship between their reported spironolactone dosage and their canrenone levels, something not seen in the Russian patients. These new findings, plus the evidence cited in the 2015 analysis, create a compelling case that “actual use of spironolactone in Russia was lower than reported” by the trial participants in Russia and probably in Georgia as well, Dr. O’Meara said. The implication is that spironolactone’s real impact on HFpEF patients is best represented in the 51% of TOPCAT patients from the Americas, she added.
“We believe these findings emphasize the reliability of the Americas data,” said Marc A. Pfeffer, MD, a coinvestigator for TOPCAT and lead author of the 2015 post hoc analysis. “Until someone comes up with a better treatment for patients with HFpEF, we should pay attention to this. People need to get this message. And spironolactone costs 7 cents a day,” said Dr. Pfeffer, professor of medicine at Harvard Medical School in Boston.Currently, no agent is considered proven effective for improving outcomes in HFpEF patients. The 2016 guidelinesfor heart failure treatment from the European Society of Cardiology said “no treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF.”
After the TOPCAT results and post hoc analysis came out in 2014 and 2015 and word spread of spironolactone’s apparent efficacy in the American half of the trial, use of spironolactone to treat HFpEF patient has increased, commented Margaret M. Redfield, MD, a heart failure physician and professor at the Mayo Clinic in Rochester, Minn. She said she often prescribes spironolactone patients to HFpEF patients who require potassium supplementation, generally because of their diuretic treatment. These are the “safest” HFpEF patients for spironolactone treatment, she said, because they face the lowest risk for hyperkalemia, the major adverse effect from spironolactone.
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point: A post hoc analysis of spironolactone use among TOPCAT participants further fueled the idea that spironolactone provides real benefit to patients with HFpEF.
Major finding: Among patients reportedly taking spironolactone, 30% of tested Russians and 3% of tested Americans did not have detectable canrenone levels.
Data source: TOPCAT, a multicenter, randomized trial with 3,445 HFpEF patients.
Disclosures: TOPCAT received no commercial funding. Dr. O’Meara, Dr. Pfeffer, and Dr. Redfield had no relevant disclosures.
AAP report flags risks of prescribing codeine for children
The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.
“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”
Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.
Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.
The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.
Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.
Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.
“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.
The report did not use external funding, and the authors reported no relevant financial disclosures.
Our scientific understanding of the underlying mechanism for respiratory suppression sometimes seen in children taking codeine is increasing, but these safety concerns aren’t new. The clinical report from Tobias et al. provides a timeline for our awareness of, and organizational response to, the reports of adverse events that goes back several years. Sadly, the investigators also provide evidence that codeine prescription patterns haven’t significantly changed, even among pediatric medical professionals.
Change is difficult in all aspects of life, and medical practice is no different. But as pediatric caregivers, the burden is on us to model safe and effective pain management. There is simply no excuse for our continued prescription of a drug with questionable benefit that, in many patients, has such an unfavorable risk-benefit ratio. And this concern is even greater when codeine is recommended for pediatric cough, an indication lacking solid evidence of benefit.
Unfortunately, there are limited pharmaceutical options for treating pediatric pain and cough, and we are often compelled to attempt to fit our square pegs into the round hole of adult medicine. The report’s authors point out that perhaps maximizing the effectiveness of drugs with proven track records in children should be the focus of our efforts. Although not mentioned in the report, benefits from the low-hanging fruit of science-based nonpharmaceutical approaches should be similarly prioritized.
These comments were provided by Clay Jones, M.D., a neonatal hospitalist at Wellesley (Mass.) Hospital. Dr. Jones had no relevant financial disclosures.
Our scientific understanding of the underlying mechanism for respiratory suppression sometimes seen in children taking codeine is increasing, but these safety concerns aren’t new. The clinical report from Tobias et al. provides a timeline for our awareness of, and organizational response to, the reports of adverse events that goes back several years. Sadly, the investigators also provide evidence that codeine prescription patterns haven’t significantly changed, even among pediatric medical professionals.
Change is difficult in all aspects of life, and medical practice is no different. But as pediatric caregivers, the burden is on us to model safe and effective pain management. There is simply no excuse for our continued prescription of a drug with questionable benefit that, in many patients, has such an unfavorable risk-benefit ratio. And this concern is even greater when codeine is recommended for pediatric cough, an indication lacking solid evidence of benefit.
Unfortunately, there are limited pharmaceutical options for treating pediatric pain and cough, and we are often compelled to attempt to fit our square pegs into the round hole of adult medicine. The report’s authors point out that perhaps maximizing the effectiveness of drugs with proven track records in children should be the focus of our efforts. Although not mentioned in the report, benefits from the low-hanging fruit of science-based nonpharmaceutical approaches should be similarly prioritized.
These comments were provided by Clay Jones, M.D., a neonatal hospitalist at Wellesley (Mass.) Hospital. Dr. Jones had no relevant financial disclosures.
Our scientific understanding of the underlying mechanism for respiratory suppression sometimes seen in children taking codeine is increasing, but these safety concerns aren’t new. The clinical report from Tobias et al. provides a timeline for our awareness of, and organizational response to, the reports of adverse events that goes back several years. Sadly, the investigators also provide evidence that codeine prescription patterns haven’t significantly changed, even among pediatric medical professionals.
Change is difficult in all aspects of life, and medical practice is no different. But as pediatric caregivers, the burden is on us to model safe and effective pain management. There is simply no excuse for our continued prescription of a drug with questionable benefit that, in many patients, has such an unfavorable risk-benefit ratio. And this concern is even greater when codeine is recommended for pediatric cough, an indication lacking solid evidence of benefit.
Unfortunately, there are limited pharmaceutical options for treating pediatric pain and cough, and we are often compelled to attempt to fit our square pegs into the round hole of adult medicine. The report’s authors point out that perhaps maximizing the effectiveness of drugs with proven track records in children should be the focus of our efforts. Although not mentioned in the report, benefits from the low-hanging fruit of science-based nonpharmaceutical approaches should be similarly prioritized.
These comments were provided by Clay Jones, M.D., a neonatal hospitalist at Wellesley (Mass.) Hospital. Dr. Jones had no relevant financial disclosures.
The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.
“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”
Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.
Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.
The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.
Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.
Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.
“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.
The report did not use external funding, and the authors reported no relevant financial disclosures.
The risks of using codeine to treat pain or cough in children may often outweigh the benefits, sometimes even leading to death, and call into question whether its widespread use should continue in pediatric patients, according to an American Academy of Pediatrics technical report.
“It is clear that one of the keys to improving analgesia and reducing opioid-related adverse effects is both provider and parental education regarding the effective use of nonopioid analgesics,” wrote Joseph D. Tobias, MD, and his colleagues from the AAP Committee on Drugs’ Section on Anesthesiology and Pain Medicine (Pediatrics 2016 Sept 19. doi: 10.1542/peds.2016-2396). “The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available.”
Individual patients respond differently to codeine because the conversion rates of the liver enzyme that metabolizes codeine into morphine, CYP2D6, vary greatly according to genetic differences. Some children experience no therapeutic effect at all while others have stopped breathing or died, particularly those who metabolize the drug extremely rapidly. Those with at least two copies of the CYP2D6 gene have a particularly elevated level of enzyme activity. Also at high risk for respiratory depression or death are children with obstructive sleep apnea.
Poor metabolizers, who therefore experience less effect from codeine, include disproportionately more individuals of Northern European descent. Ultrarapid metabolizers, on the other hand, comprise approximately 29% of patients of African/Ethiopian heritage and 21% from Middle Eastern countries. An estimated 3.4%-6.5% of African Americans and whites are ultrafast metabolizers. Genetic tests can identify those at higher risk, but even children with normal metabolism can experience severe adverse effects.
The World Health Organization removed codeine from its list of essential medications, the U.S. Food and Drug Administration added a black box warning to labels of codeine formulations used for tonsillectomy and/or adenoidectomy in children, and the European Medicines Agency recommended against using codeine in children under age 12 years and in those between 12 and 18 years who have breathing difficulties.
Yet research has shown that the use of codeine for pain relief in children remains very common; codeine is prescribed more than any other opioid in some studies. Otolaryngologists, dentists, pediatricians, and family practice physicians, respectively, prescribe it most often, likely because few safe, effective therapeutics exist for treating pain or cough in children. Oxycodone has been used as an alternative, but this drug also lacks adequate data on its use, and hydrocodone has similar concerns with rapid metabolizers.
Although most of the serious adverse events resulting in codeine use in children have followed adenotonsillectomy in children with disordered breathing, the authors warned that “physicians cannot assume such problems will occur only” after such procedures.
“Given the increasing prevalence of obesity in the United States, it is likely that some patients presenting for nonotolaryngologic procedures may have undiagnosed sleep-disordered breathing and may also be at risk if they require extended postoperative analgesia,” they wrote. They called for better parental education regarding pain relief and more formal restrictions for its use in pediatrics.
The report did not use external funding, and the authors reported no relevant financial disclosures.
FROM PEDIATRICS
Key clinical point: Codeine use in children carries significant risks, such as breathing depression and death.
Major finding: Children with African/Ethiopian and Middle Eastern descent are more likely to be rapid metabolizers of codeine and at greater risk for serious adverse effects.
Data source: A review of the most current literature on the adverse effects of codeine use in pediatric patients and guidance issued by regulatory and professional medical organizations.
Disclosures: The report did not use external funding, and the authors reported no relevant financial disclosures.
Poll: Patients oppose extended resident work hours
The majority of patients support work-hour limits for medical residents and want tighter shift caps for second-year residents and above, according to a national poll published Sept. 13 by Public Citizen.
The survey of 500 consumers by Lake Research Partners found that 86% of respondents were opposed to eliminating the Accreditation Council for Graduate Medical Education’s (ACGME) current 16-hour shift limit for first-year residents. Most respondents (80%) also favor decreasing the shift limit from 28 hours to 16 hours for second-year residents and above. More than three-quarters of respondents said hospital patients should be informed if a medical resident treating them has been working more than 16 hours without sleep.
“The public’s apprehension about resident shifts longer than 16 hours comports with the long-standing evidence on the risks of long resident work shifts for both the residents and their patients,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said during a press conference. “Medical residents are not superhuman and, when sleep-deprived, put themselves, their patients, and others in harm’s way. This is not a partisan political issue, but one of public health and safety.”
But some physicians called the findings “obvious” and said they fail to address the full picture of work-hour limitations for residents. Evaluating only one aspect of a complex problem risks causing harm through unintended consequences, said Sharmila Dissanaike, MD, Peter C. Canizaro Chair of Surgery at Texas Tech University Health Sciences Center in Lubbock.
“The poll reflects that the public would prefer a well-rested physician over a sleep-deprived one – an obvious finding – since we would all prefer our physicians, nurses, police officers, firemen, and anyone who provides essential care or services to us to be well rested,” Dr. Dissanaike said in an interview. “However, interpreting this result as a mandate from the public to increase restrictions on resident duty hours, while well intentioned, is shortsighted and neglects many salient aspects of the problem, including the high risk of increased handoffs and adverse impact on GME training as a whole.”
The poll is the latest development in an ongoing debate about resident work hours and whether cutting shift time for new doctors aids or undermines patient safety. Earlier this year, a host of physician associations called on ACGME to roll back its work limits on first-year residents. The medical associations say current duty-hour restrictions are not improving care, and that the limits are negatively impacting physician training. The American College of Surgeons (ACS) for example, recommends the only restrictions on resident duty hours be a total of 80 hours per week, averaged over a 4-week period, with no other limitations.
The physician associations note a recent landmark study of 117 general surgery residency programs that found longer shifts have not markedly affected patient outcomes. The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial, published Feb. 25 in the New England Journal of Medicine, showed extended work hours for residents are not associated with a greater risk of early serious postoperative complications or death (N Engl J Med. 2016;374:713-27). Other studies have found similar results.
During a Sept. 13 press conference, Public Citizen representatives called the FIRST study and ongoing iCOMPARE trials “unethical.” The studies have forced some first-year residents to work shifts of 28 consecutive hours or more without their consent or the consent of patients, Dr. Carome said. When polled, 84% of survey respondents said if admitted to a hospital, they would want to know if their health provider was participating in such trials. Public Citizen and the American Medical Student Association have requested prompt investigation and suspension of the trials by the Office for Human Research Protections and have urged ACGME not to allow the trials to continue.
Sleep-deprived physicians are more prone to making errors, injuring themselves, and incurring chronic health ailments, said Charles A. Czeisler, PhD, MD, chief of the division of sleep and circadian disorders at Brigham & Women’s Hospital and director of the division of sleep medicine at Harvard University School of Medicine, Boston.
“One of the concerns of the extended-duration shifts that resident physicians work is the impairment of performance,” Dr. Czeisler said during the press conference. “We know when an individual is awake for more than 24 hours, their performance is impaired by an amount that is equivalent to that of being legally drunk.”
Research shows that resident physicians working in intensive care units make 36% more serious medical errors on patients whom they are treating while working marathon extended duration shifts, Dr. Czeisler said. In addition, physicians have a 460% higher risk of diagnostic errors when working extended shifts, he added. Stressing this evidence, Public Citizen and others have called on ACGME to reject scaling back its 16-hour work-shift limit for first-year residents.
But restricting physician work hours to improve patient safety and care quality is not as straightforward as it seems, said Patrick C. Alguire, MD, senior vice president for medical education at the American College of Physicians. Physician-scientists who study the process have found unintended consequences of restricted working hours and unfulfilled expectations, Dr. Alguire said in an interview.
“The weight of the evidence does not demonstrate improvement in patient outcomes such as mortality or safety, consistent positive impact on resident wellness, or even meaningful gains in resident sleep,” he said. “Moreover, restrictive scheduling assignments shorten the time for residents to complete their work, resulting in heightened work intensity and resident stress and inability to balance work and educational responsibilities. Scheduling restrictions have also increased the proportion of night float rotations and ACP finds these of less educational value than daytime rotations.”
Most concerning is that scheduling restrictions increase the opportunity for errors due to the frequency of handoffs from one team to another, Dr. Alguire said. The ACP recommends that ACGME undertake a critical review of scheduling restrictions focusing on added flexibility that takes into account patient care complexity, intensity, and acuity, as well as local factors, he added.
“It is ACP’s opinion that the ACGME should allow deviations from the existing schedule limitations within the context of approved studies, the results of which will provide the ACGME with a firmer evidence base upon which to optimize the inpatient clinical learning environment and the safety and well-being of both residents and patients,” Dr. Alguire said.
On Twitter @legal_med
The majority of patients support work-hour limits for medical residents and want tighter shift caps for second-year residents and above, according to a national poll published Sept. 13 by Public Citizen.
The survey of 500 consumers by Lake Research Partners found that 86% of respondents were opposed to eliminating the Accreditation Council for Graduate Medical Education’s (ACGME) current 16-hour shift limit for first-year residents. Most respondents (80%) also favor decreasing the shift limit from 28 hours to 16 hours for second-year residents and above. More than three-quarters of respondents said hospital patients should be informed if a medical resident treating them has been working more than 16 hours without sleep.
“The public’s apprehension about resident shifts longer than 16 hours comports with the long-standing evidence on the risks of long resident work shifts for both the residents and their patients,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said during a press conference. “Medical residents are not superhuman and, when sleep-deprived, put themselves, their patients, and others in harm’s way. This is not a partisan political issue, but one of public health and safety.”
But some physicians called the findings “obvious” and said they fail to address the full picture of work-hour limitations for residents. Evaluating only one aspect of a complex problem risks causing harm through unintended consequences, said Sharmila Dissanaike, MD, Peter C. Canizaro Chair of Surgery at Texas Tech University Health Sciences Center in Lubbock.
“The poll reflects that the public would prefer a well-rested physician over a sleep-deprived one – an obvious finding – since we would all prefer our physicians, nurses, police officers, firemen, and anyone who provides essential care or services to us to be well rested,” Dr. Dissanaike said in an interview. “However, interpreting this result as a mandate from the public to increase restrictions on resident duty hours, while well intentioned, is shortsighted and neglects many salient aspects of the problem, including the high risk of increased handoffs and adverse impact on GME training as a whole.”
The poll is the latest development in an ongoing debate about resident work hours and whether cutting shift time for new doctors aids or undermines patient safety. Earlier this year, a host of physician associations called on ACGME to roll back its work limits on first-year residents. The medical associations say current duty-hour restrictions are not improving care, and that the limits are negatively impacting physician training. The American College of Surgeons (ACS) for example, recommends the only restrictions on resident duty hours be a total of 80 hours per week, averaged over a 4-week period, with no other limitations.
The physician associations note a recent landmark study of 117 general surgery residency programs that found longer shifts have not markedly affected patient outcomes. The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial, published Feb. 25 in the New England Journal of Medicine, showed extended work hours for residents are not associated with a greater risk of early serious postoperative complications or death (N Engl J Med. 2016;374:713-27). Other studies have found similar results.
During a Sept. 13 press conference, Public Citizen representatives called the FIRST study and ongoing iCOMPARE trials “unethical.” The studies have forced some first-year residents to work shifts of 28 consecutive hours or more without their consent or the consent of patients, Dr. Carome said. When polled, 84% of survey respondents said if admitted to a hospital, they would want to know if their health provider was participating in such trials. Public Citizen and the American Medical Student Association have requested prompt investigation and suspension of the trials by the Office for Human Research Protections and have urged ACGME not to allow the trials to continue.
Sleep-deprived physicians are more prone to making errors, injuring themselves, and incurring chronic health ailments, said Charles A. Czeisler, PhD, MD, chief of the division of sleep and circadian disorders at Brigham & Women’s Hospital and director of the division of sleep medicine at Harvard University School of Medicine, Boston.
“One of the concerns of the extended-duration shifts that resident physicians work is the impairment of performance,” Dr. Czeisler said during the press conference. “We know when an individual is awake for more than 24 hours, their performance is impaired by an amount that is equivalent to that of being legally drunk.”
Research shows that resident physicians working in intensive care units make 36% more serious medical errors on patients whom they are treating while working marathon extended duration shifts, Dr. Czeisler said. In addition, physicians have a 460% higher risk of diagnostic errors when working extended shifts, he added. Stressing this evidence, Public Citizen and others have called on ACGME to reject scaling back its 16-hour work-shift limit for first-year residents.
But restricting physician work hours to improve patient safety and care quality is not as straightforward as it seems, said Patrick C. Alguire, MD, senior vice president for medical education at the American College of Physicians. Physician-scientists who study the process have found unintended consequences of restricted working hours and unfulfilled expectations, Dr. Alguire said in an interview.
“The weight of the evidence does not demonstrate improvement in patient outcomes such as mortality or safety, consistent positive impact on resident wellness, or even meaningful gains in resident sleep,” he said. “Moreover, restrictive scheduling assignments shorten the time for residents to complete their work, resulting in heightened work intensity and resident stress and inability to balance work and educational responsibilities. Scheduling restrictions have also increased the proportion of night float rotations and ACP finds these of less educational value than daytime rotations.”
Most concerning is that scheduling restrictions increase the opportunity for errors due to the frequency of handoffs from one team to another, Dr. Alguire said. The ACP recommends that ACGME undertake a critical review of scheduling restrictions focusing on added flexibility that takes into account patient care complexity, intensity, and acuity, as well as local factors, he added.
“It is ACP’s opinion that the ACGME should allow deviations from the existing schedule limitations within the context of approved studies, the results of which will provide the ACGME with a firmer evidence base upon which to optimize the inpatient clinical learning environment and the safety and well-being of both residents and patients,” Dr. Alguire said.
On Twitter @legal_med
The majority of patients support work-hour limits for medical residents and want tighter shift caps for second-year residents and above, according to a national poll published Sept. 13 by Public Citizen.
The survey of 500 consumers by Lake Research Partners found that 86% of respondents were opposed to eliminating the Accreditation Council for Graduate Medical Education’s (ACGME) current 16-hour shift limit for first-year residents. Most respondents (80%) also favor decreasing the shift limit from 28 hours to 16 hours for second-year residents and above. More than three-quarters of respondents said hospital patients should be informed if a medical resident treating them has been working more than 16 hours without sleep.
“The public’s apprehension about resident shifts longer than 16 hours comports with the long-standing evidence on the risks of long resident work shifts for both the residents and their patients,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said during a press conference. “Medical residents are not superhuman and, when sleep-deprived, put themselves, their patients, and others in harm’s way. This is not a partisan political issue, but one of public health and safety.”
But some physicians called the findings “obvious” and said they fail to address the full picture of work-hour limitations for residents. Evaluating only one aspect of a complex problem risks causing harm through unintended consequences, said Sharmila Dissanaike, MD, Peter C. Canizaro Chair of Surgery at Texas Tech University Health Sciences Center in Lubbock.
“The poll reflects that the public would prefer a well-rested physician over a sleep-deprived one – an obvious finding – since we would all prefer our physicians, nurses, police officers, firemen, and anyone who provides essential care or services to us to be well rested,” Dr. Dissanaike said in an interview. “However, interpreting this result as a mandate from the public to increase restrictions on resident duty hours, while well intentioned, is shortsighted and neglects many salient aspects of the problem, including the high risk of increased handoffs and adverse impact on GME training as a whole.”
The poll is the latest development in an ongoing debate about resident work hours and whether cutting shift time for new doctors aids or undermines patient safety. Earlier this year, a host of physician associations called on ACGME to roll back its work limits on first-year residents. The medical associations say current duty-hour restrictions are not improving care, and that the limits are negatively impacting physician training. The American College of Surgeons (ACS) for example, recommends the only restrictions on resident duty hours be a total of 80 hours per week, averaged over a 4-week period, with no other limitations.
The physician associations note a recent landmark study of 117 general surgery residency programs that found longer shifts have not markedly affected patient outcomes. The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial, published Feb. 25 in the New England Journal of Medicine, showed extended work hours for residents are not associated with a greater risk of early serious postoperative complications or death (N Engl J Med. 2016;374:713-27). Other studies have found similar results.
During a Sept. 13 press conference, Public Citizen representatives called the FIRST study and ongoing iCOMPARE trials “unethical.” The studies have forced some first-year residents to work shifts of 28 consecutive hours or more without their consent or the consent of patients, Dr. Carome said. When polled, 84% of survey respondents said if admitted to a hospital, they would want to know if their health provider was participating in such trials. Public Citizen and the American Medical Student Association have requested prompt investigation and suspension of the trials by the Office for Human Research Protections and have urged ACGME not to allow the trials to continue.
Sleep-deprived physicians are more prone to making errors, injuring themselves, and incurring chronic health ailments, said Charles A. Czeisler, PhD, MD, chief of the division of sleep and circadian disorders at Brigham & Women’s Hospital and director of the division of sleep medicine at Harvard University School of Medicine, Boston.
“One of the concerns of the extended-duration shifts that resident physicians work is the impairment of performance,” Dr. Czeisler said during the press conference. “We know when an individual is awake for more than 24 hours, their performance is impaired by an amount that is equivalent to that of being legally drunk.”
Research shows that resident physicians working in intensive care units make 36% more serious medical errors on patients whom they are treating while working marathon extended duration shifts, Dr. Czeisler said. In addition, physicians have a 460% higher risk of diagnostic errors when working extended shifts, he added. Stressing this evidence, Public Citizen and others have called on ACGME to reject scaling back its 16-hour work-shift limit for first-year residents.
But restricting physician work hours to improve patient safety and care quality is not as straightforward as it seems, said Patrick C. Alguire, MD, senior vice president for medical education at the American College of Physicians. Physician-scientists who study the process have found unintended consequences of restricted working hours and unfulfilled expectations, Dr. Alguire said in an interview.
“The weight of the evidence does not demonstrate improvement in patient outcomes such as mortality or safety, consistent positive impact on resident wellness, or even meaningful gains in resident sleep,” he said. “Moreover, restrictive scheduling assignments shorten the time for residents to complete their work, resulting in heightened work intensity and resident stress and inability to balance work and educational responsibilities. Scheduling restrictions have also increased the proportion of night float rotations and ACP finds these of less educational value than daytime rotations.”
Most concerning is that scheduling restrictions increase the opportunity for errors due to the frequency of handoffs from one team to another, Dr. Alguire said. The ACP recommends that ACGME undertake a critical review of scheduling restrictions focusing on added flexibility that takes into account patient care complexity, intensity, and acuity, as well as local factors, he added.
“It is ACP’s opinion that the ACGME should allow deviations from the existing schedule limitations within the context of approved studies, the results of which will provide the ACGME with a firmer evidence base upon which to optimize the inpatient clinical learning environment and the safety and well-being of both residents and patients,” Dr. Alguire said.
On Twitter @legal_med
FRAIL scale found to predict 1-year functional status of geriatric trauma patients
WAIKOLOA, HAWAII – The FRAIL scale questionnaire predicts functional status and mortality at 1 year among geriatric trauma patients and is a useful tool for bedside screening by clinicians, results from a single-center study demonstrated.
“Over the past 2 years, the implications of frailty among the geriatric trauma population have gained much attention in the trauma community,” Cathy A. Maxwell, PhD, RN, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “This work highlights the clinical utility of the FRAIL scale for screening injured older patients who are admitted to trauma centers and other acute care hospitals. Hopefully, it will encourage trauma care providers to use the instrument to identify older patients’ pre-injury/baseline status and to obtain a frailty risk adjustment measure for quality improvement efforts.”
Developed by the International Association of Nutrition and Aging, the validated five-item FRAIL scale requires answers to questions about fatigue, resistance, ambulation, illnesses, and loss of weight (J Nutr Health Aging. 2012;16[7]:601-8). In an effort to examine the influence of pre-injury physical frailty (as measured by FRAIL) on 1-year outcomes, Dr. Maxwell, of the Vanderbilt University, Nashville, Tenn., and her associates evaluated injured patients aged 65 and older who were admitted through the ED between October 2013 and March 2014 and who participated in a prior study (J Trauma Acute Care Surg. 2016;80[2]:195-203). The researchers identified the five items of the FRAIL instrument from that study and created a pre-injury FRAIL score for each patient.
Dr. Maxwell reported results from 188 patients with a median age of 77, a median Injury Severity Score of 10, and a median comorbidity index of 3. Upon admission to the ED, 63 patients (34%) screened as frail (defined as a FRAIL score of 3 or greater), 71 (38%) screened as pre-frail (defined as a FRAIL score of 1-2), and 54 (29%) screened as non-frail (defined as a FRAIL score of zero). Frequencies for components of the FRAIL score were as follows: fatigue (65%), resistance (32%), ambulation (40%), illnesses (27%), and loss of weight (6%).
After the researchers controlled for age, comorbidities, injury severity, and cognitive status via the Ascertain Dementia 8-item Informant Questionnaire (AD8), they found that pre-injury FRAIL scores explained about 13% of the variability in physical function as measured by the Barthel Index (P less than .001). A total of 47 patients (26%) died within 1 year of admission. Logistic regression analysis revealed that after adjustment for these same variables, the higher the pre-injury FRAIL score, the greater the likelihood of mortality within 1 year (odds ratio, 1.74; P = .001).
“The FRAIL scale predicts functional decline and mortality in geriatric trauma patients and is a useful tool for clinicians,” Dr. Maxwell concluded. “Bedside nurses in our trauma unit at Vanderbilt University Medical Center are currently using this instrument to screen our older patients. We have seen an increase in earlier geriatric palliative care consultations as a result of our screening efforts.”
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis. “We created FRAIL scale scores for 188 patients from six different data sources, thus, the created scores may not accurately represent actual prospectively collected FRAIL scores,” Dr. Maxwell said. “That being said, we compared the frailty frequencies from this study with actual FRAIL scale scores (from current bedside FRAIL screens) and we are seeing similar percentages of patients in non-frail, pre-frail and frail categories. This strengthens the findings of this study.”
She reported having no financial disclosures.
WAIKOLOA, HAWAII – The FRAIL scale questionnaire predicts functional status and mortality at 1 year among geriatric trauma patients and is a useful tool for bedside screening by clinicians, results from a single-center study demonstrated.
“Over the past 2 years, the implications of frailty among the geriatric trauma population have gained much attention in the trauma community,” Cathy A. Maxwell, PhD, RN, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “This work highlights the clinical utility of the FRAIL scale for screening injured older patients who are admitted to trauma centers and other acute care hospitals. Hopefully, it will encourage trauma care providers to use the instrument to identify older patients’ pre-injury/baseline status and to obtain a frailty risk adjustment measure for quality improvement efforts.”
Developed by the International Association of Nutrition and Aging, the validated five-item FRAIL scale requires answers to questions about fatigue, resistance, ambulation, illnesses, and loss of weight (J Nutr Health Aging. 2012;16[7]:601-8). In an effort to examine the influence of pre-injury physical frailty (as measured by FRAIL) on 1-year outcomes, Dr. Maxwell, of the Vanderbilt University, Nashville, Tenn., and her associates evaluated injured patients aged 65 and older who were admitted through the ED between October 2013 and March 2014 and who participated in a prior study (J Trauma Acute Care Surg. 2016;80[2]:195-203). The researchers identified the five items of the FRAIL instrument from that study and created a pre-injury FRAIL score for each patient.
Dr. Maxwell reported results from 188 patients with a median age of 77, a median Injury Severity Score of 10, and a median comorbidity index of 3. Upon admission to the ED, 63 patients (34%) screened as frail (defined as a FRAIL score of 3 or greater), 71 (38%) screened as pre-frail (defined as a FRAIL score of 1-2), and 54 (29%) screened as non-frail (defined as a FRAIL score of zero). Frequencies for components of the FRAIL score were as follows: fatigue (65%), resistance (32%), ambulation (40%), illnesses (27%), and loss of weight (6%).
After the researchers controlled for age, comorbidities, injury severity, and cognitive status via the Ascertain Dementia 8-item Informant Questionnaire (AD8), they found that pre-injury FRAIL scores explained about 13% of the variability in physical function as measured by the Barthel Index (P less than .001). A total of 47 patients (26%) died within 1 year of admission. Logistic regression analysis revealed that after adjustment for these same variables, the higher the pre-injury FRAIL score, the greater the likelihood of mortality within 1 year (odds ratio, 1.74; P = .001).
“The FRAIL scale predicts functional decline and mortality in geriatric trauma patients and is a useful tool for clinicians,” Dr. Maxwell concluded. “Bedside nurses in our trauma unit at Vanderbilt University Medical Center are currently using this instrument to screen our older patients. We have seen an increase in earlier geriatric palliative care consultations as a result of our screening efforts.”
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis. “We created FRAIL scale scores for 188 patients from six different data sources, thus, the created scores may not accurately represent actual prospectively collected FRAIL scores,” Dr. Maxwell said. “That being said, we compared the frailty frequencies from this study with actual FRAIL scale scores (from current bedside FRAIL screens) and we are seeing similar percentages of patients in non-frail, pre-frail and frail categories. This strengthens the findings of this study.”
She reported having no financial disclosures.
WAIKOLOA, HAWAII – The FRAIL scale questionnaire predicts functional status and mortality at 1 year among geriatric trauma patients and is a useful tool for bedside screening by clinicians, results from a single-center study demonstrated.
“Over the past 2 years, the implications of frailty among the geriatric trauma population have gained much attention in the trauma community,” Cathy A. Maxwell, PhD, RN, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “This work highlights the clinical utility of the FRAIL scale for screening injured older patients who are admitted to trauma centers and other acute care hospitals. Hopefully, it will encourage trauma care providers to use the instrument to identify older patients’ pre-injury/baseline status and to obtain a frailty risk adjustment measure for quality improvement efforts.”
Developed by the International Association of Nutrition and Aging, the validated five-item FRAIL scale requires answers to questions about fatigue, resistance, ambulation, illnesses, and loss of weight (J Nutr Health Aging. 2012;16[7]:601-8). In an effort to examine the influence of pre-injury physical frailty (as measured by FRAIL) on 1-year outcomes, Dr. Maxwell, of the Vanderbilt University, Nashville, Tenn., and her associates evaluated injured patients aged 65 and older who were admitted through the ED between October 2013 and March 2014 and who participated in a prior study (J Trauma Acute Care Surg. 2016;80[2]:195-203). The researchers identified the five items of the FRAIL instrument from that study and created a pre-injury FRAIL score for each patient.
Dr. Maxwell reported results from 188 patients with a median age of 77, a median Injury Severity Score of 10, and a median comorbidity index of 3. Upon admission to the ED, 63 patients (34%) screened as frail (defined as a FRAIL score of 3 or greater), 71 (38%) screened as pre-frail (defined as a FRAIL score of 1-2), and 54 (29%) screened as non-frail (defined as a FRAIL score of zero). Frequencies for components of the FRAIL score were as follows: fatigue (65%), resistance (32%), ambulation (40%), illnesses (27%), and loss of weight (6%).
After the researchers controlled for age, comorbidities, injury severity, and cognitive status via the Ascertain Dementia 8-item Informant Questionnaire (AD8), they found that pre-injury FRAIL scores explained about 13% of the variability in physical function as measured by the Barthel Index (P less than .001). A total of 47 patients (26%) died within 1 year of admission. Logistic regression analysis revealed that after adjustment for these same variables, the higher the pre-injury FRAIL score, the greater the likelihood of mortality within 1 year (odds ratio, 1.74; P = .001).
“The FRAIL scale predicts functional decline and mortality in geriatric trauma patients and is a useful tool for clinicians,” Dr. Maxwell concluded. “Bedside nurses in our trauma unit at Vanderbilt University Medical Center are currently using this instrument to screen our older patients. We have seen an increase in earlier geriatric palliative care consultations as a result of our screening efforts.”
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis. “We created FRAIL scale scores for 188 patients from six different data sources, thus, the created scores may not accurately represent actual prospectively collected FRAIL scores,” Dr. Maxwell said. “That being said, we compared the frailty frequencies from this study with actual FRAIL scale scores (from current bedside FRAIL screens) and we are seeing similar percentages of patients in non-frail, pre-frail and frail categories. This strengthens the findings of this study.”
She reported having no financial disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point: The FRAIL scale is a useful tool for bedside screening of geriatric trauma patients.
Major finding: On logistic regression analysis, the higher the pre-injury FRAIL score, the greater the likelihood of mortality within 1 year (OR = 1.74; P = .001).
Data source: A secondary analysis of 188 injured patients aged 65 and older who were admitted through the ED between October 2013 and March 2014.
Disclosures: Dr. Maxwell reported having no financial disclosures.
Study suggests link between commonly used antihypertensive drug and skin cancer
Despite its widespread use as a guideline-recommended, first-line agent for the treatment of hypertension, hydrochlorothiazide (HCTZ) may contribute to an increased risk of skin cancer, according to Armand B. Cognetta Jr., MD, and his associates in the division of dermatology, Mohs Micrographic Surgery Unit, Florida State University, Tallahassee.
The common, long-term use of HCTZ for treatment of hypertension, combined with its known photosensitizing effects, makes it a potential candidate for increasing the risk of squamous cell carcinoma (SCC) and other skin cancers.
To further elucidate the association between longterm HCTZ exposure and skin cancer risk, Dr. Cognetta and his associates screened medication lists of 75 patients seen in their Mohs practice over a period of 5 days for lifetime SCCs and HCTZ exposure. For this study, patients with more than 20 lifetime SCCs were considered high risk. They also conducted a literature review of previous studies exploring this relationship, from 1966 to 2015.
Of the 75 patients screened, 4 met the criteria for inclusion in the high risk category. These four patients had a combined lifetime total of 288 SCC and 98 basal cell carcinomas (BCCs), including 10 that were lip SCC. All four patients were non-Hispanic white males and had been taking HCTZ alone or in combination for 3-15 years (Dermatol Surg. 2016 Sep;42[9]:1107-9).
The literature search produced three relevant studies, all of which had large patient populations, published between 2008 and 2012, “demonstrating an increased risk of SCC or lip cancer” associated with HCTZ use, with the highest risk associated with over 5 years of use, the researchers wrote.
“As cutaneous oncologists, it is our duty to look for ‘correctable’ causes of skin cancer,” they noted. “Hydrochlorothiazide, a known photosensitizer, when taken by white non-Hispanic patients with a history of multiple SCC, skin cancers may represent a ‘correctable’ cause.”
In their practice, they screen their high-risk SCC non-Hispanic patients for HCTZ use, “and send a standard letter explaining the association to the primary care provider with a request to change to a different antihypertensive if possible,” they wrote. “Many primary care providers are unaware of the association between HCTZ use and skin cancer,” they observed.
The authors had no disclosures.
Despite its widespread use as a guideline-recommended, first-line agent for the treatment of hypertension, hydrochlorothiazide (HCTZ) may contribute to an increased risk of skin cancer, according to Armand B. Cognetta Jr., MD, and his associates in the division of dermatology, Mohs Micrographic Surgery Unit, Florida State University, Tallahassee.
The common, long-term use of HCTZ for treatment of hypertension, combined with its known photosensitizing effects, makes it a potential candidate for increasing the risk of squamous cell carcinoma (SCC) and other skin cancers.
To further elucidate the association between longterm HCTZ exposure and skin cancer risk, Dr. Cognetta and his associates screened medication lists of 75 patients seen in their Mohs practice over a period of 5 days for lifetime SCCs and HCTZ exposure. For this study, patients with more than 20 lifetime SCCs were considered high risk. They also conducted a literature review of previous studies exploring this relationship, from 1966 to 2015.
Of the 75 patients screened, 4 met the criteria for inclusion in the high risk category. These four patients had a combined lifetime total of 288 SCC and 98 basal cell carcinomas (BCCs), including 10 that were lip SCC. All four patients were non-Hispanic white males and had been taking HCTZ alone or in combination for 3-15 years (Dermatol Surg. 2016 Sep;42[9]:1107-9).
The literature search produced three relevant studies, all of which had large patient populations, published between 2008 and 2012, “demonstrating an increased risk of SCC or lip cancer” associated with HCTZ use, with the highest risk associated with over 5 years of use, the researchers wrote.
“As cutaneous oncologists, it is our duty to look for ‘correctable’ causes of skin cancer,” they noted. “Hydrochlorothiazide, a known photosensitizer, when taken by white non-Hispanic patients with a history of multiple SCC, skin cancers may represent a ‘correctable’ cause.”
In their practice, they screen their high-risk SCC non-Hispanic patients for HCTZ use, “and send a standard letter explaining the association to the primary care provider with a request to change to a different antihypertensive if possible,” they wrote. “Many primary care providers are unaware of the association between HCTZ use and skin cancer,” they observed.
The authors had no disclosures.
Despite its widespread use as a guideline-recommended, first-line agent for the treatment of hypertension, hydrochlorothiazide (HCTZ) may contribute to an increased risk of skin cancer, according to Armand B. Cognetta Jr., MD, and his associates in the division of dermatology, Mohs Micrographic Surgery Unit, Florida State University, Tallahassee.
The common, long-term use of HCTZ for treatment of hypertension, combined with its known photosensitizing effects, makes it a potential candidate for increasing the risk of squamous cell carcinoma (SCC) and other skin cancers.
To further elucidate the association between longterm HCTZ exposure and skin cancer risk, Dr. Cognetta and his associates screened medication lists of 75 patients seen in their Mohs practice over a period of 5 days for lifetime SCCs and HCTZ exposure. For this study, patients with more than 20 lifetime SCCs were considered high risk. They also conducted a literature review of previous studies exploring this relationship, from 1966 to 2015.
Of the 75 patients screened, 4 met the criteria for inclusion in the high risk category. These four patients had a combined lifetime total of 288 SCC and 98 basal cell carcinomas (BCCs), including 10 that were lip SCC. All four patients were non-Hispanic white males and had been taking HCTZ alone or in combination for 3-15 years (Dermatol Surg. 2016 Sep;42[9]:1107-9).
The literature search produced three relevant studies, all of which had large patient populations, published between 2008 and 2012, “demonstrating an increased risk of SCC or lip cancer” associated with HCTZ use, with the highest risk associated with over 5 years of use, the researchers wrote.
“As cutaneous oncologists, it is our duty to look for ‘correctable’ causes of skin cancer,” they noted. “Hydrochlorothiazide, a known photosensitizer, when taken by white non-Hispanic patients with a history of multiple SCC, skin cancers may represent a ‘correctable’ cause.”
In their practice, they screen their high-risk SCC non-Hispanic patients for HCTZ use, “and send a standard letter explaining the association to the primary care provider with a request to change to a different antihypertensive if possible,” they wrote. “Many primary care providers are unaware of the association between HCTZ use and skin cancer,” they observed.
The authors had no disclosures.
Key clinical point: The antihypertensive agent hydrochlorothiazide (HCTZ ) is photosensitizing and may be associated with an increased risk for skin cancers in non-Hispanic white males with a history of squamous cell carcinoma (SCC).
Major finding: All four patients considered high risk based on lifetime SCC history were non-Hispanic white males with a history of HCTZ exposure, an association supported by three previously published studies.
Data sources: Medical records from 75 patients seen in a single dermatology practice over a 5-day period, and a literature search as well as relevant publications detected through a literature search spanning the years 1966-2015.
Disclosures: The authors had no disclosures. A funding source was not identified.
Benralizumab reduces exacerbations in pivotal severe asthma trials
LONDON – The investigational treatment benralizumab significantly reduced the number of exacerbations that patients with severe, uncontrolled asthma experienced during the course of a year in two phase III studies.
In the SIROCCO and CALIMA trials, which altogether involved more than 2,000 adult patients, the annual exacerbation rate (AER) was cut by 28%-51%, compared with placebo when benralizumab was added to standard combination therapy of an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA).
Benralizumab treatment was also associated with significant improvements in lung function (up to 159 mL increase in FEV1), and reduced daily asthma symptoms of wheeze, cough, and dyspnea versus placebo. There were also improvements seen in patient-reported measures of asthma control and quality of life.
The results of these two multicenter, randomized, double-blind, placebo-controlled, parallel group studies were published in full online in The Lancet to coincide with their presentation at the annual congress of the European Respiratory Society.
Benralizumab is a humanized, monoclonal antibody that has been shown to rapidly and almost completely deplete the number of eosinophils in the blood, airways, and bone marrow, Eugene R Bleecker, MD, who presented the results of the SIROCCO study, explained at the meeting.
Dr. Bleecker, who is the director of the Center for Genomics and Personalized Medicine Research at Wake Forest University in Winston-Salem, N.C., observed that benralizumab “works a little bit differently” to other interleukin (IL)-5–targeting monoclonal antibodies, such as mepolizumab and reslizumab. Rather than target the IL-5 ligand itself, benralizumab binds to IL-5 receptors present on the surface of eosinophils. This action activates natural killer cells, which then destroy the eosinophils via antibody-dependent cell-mediated cytotoxicity.
Phase IIb data have already shown a benefit for benralizumab versus placebo in patients with uncontrolled asthma with high (300 cells/mcL or greater) eosinophil counts in the blood. The aim of the SIROCCO and CALIMA phase III trials was thus to examine the efficacy and safety of the novel agent further in this patient population.
In SIROCCO, 1,205 patients were randomized, and 1,306 were randomized in CALIMA. Key inclusion criteria were physician-diagnosed asthma requiring ICS/LABA therapy and at least two exacerbations in the past 12 months. Patients also needed to be symptomatic during a 4-week run-in period before being randomized to one of three study groups. The groups included one that received benralizumab at a subcutaneous dose of 30 mg every 4 weeks; another that received benralizumab at a subcutaneous dose of 30 mg every 4 weeks for the first three doses then a 30 mg dose or placebo injection alternating every 4 weeks; and a third group that received placebo injections every 4 weeks.
The mean age of patients in both studies and across treatment arms was broadly similar, ranging from 47 to 50 years. Around two thirds of the study population was female, with similar baseline characteristics.
The primary endpoint was the AER in patients with a blood eosinophil count of 300 cells/mcL or higher. In SIROCCO this was measured at 48 weeks and in CALIMA at 56 weeks. The respective AERs for placebo and for the 4- and 8-week dosing regimens of benralizumab were 1.33, 0.73, and 0.65 in SIROCCO and 0.93, 0.6, and 0.66 in CALIMA. This represented a 45% reduction in the AER for the 4-week and a 51% reduction for the 8-week regimens of benralizumab versus placebo in SIROCCO, and a 36% and 28% reduction, respectively, in CALIMA.
There was a large placebo effect and the overall population recruited into CALIMA may have had less severe asthma than the patients who participated in SIROCCO, the principal investigator for CALIMA, Mark FitzGerald, MD, pointed out during a press briefing organized by AstraZeneca. “But when you look at the composite of both studies together, you can see that the results are quite robust,” said Dr. FitzGerald, the director of the Centre for Lung and Heart Health at Vancouver Coastal Health Research Institute.
There was also some evidence that patients who had three or more prior exacerbations fared better, he said, highlighting the importance of defining the patient population who may benefit the most from this treatment.
Something that needs to be investigated further is why patients given the 8-week benralizumab regimen seemed to do better, at least numerically, than those given the 4-week regimen. Dr. FitzGerald suggested that “because eosinophil cells are such a powerful driver of disease, perhaps you may not actually need to be treated as frequently as historically we might have done.”
Other similar biologic agents need dosing every 2 to 4 weeks, but perhaps every 8 weeks is a possibility in the future for benralizumab. A lot can be learned from how biologics are used in rheumatology, he suggested, where treatments have started being given less frequently, because the biology of the various rheumatic diseases is now better understood.
Any adverse event was reported by a similar percentage of actively-treated (71%-75%) and placebo-treated (73%-78%) patients. The frequency and nature of other adverse events were similar to placebo.
The SIROCCO and CALIMA trial data will form part of AstraZeneca’s U.S. and EU regulatory submissions later this year for benralizumab as a treatment for severe, uncontrolled, eosinophilic asthma.
“Potentially, when it becomes available, benralizumab will provide a new therapeutic option for this class of patient.” Dr. FitzGerald said.
Benralizumab is also being investigated as a possible treatment for patients with less severe eosinophilic asthma in the BISE phase III study and as an option for those with severe chronic obstructive pulmonary disease who have high levels of eosinophils in the phase III VOYAGER program.
AstraZeneca and Kyowa Hakko Kirin funded the studies. Dr. Bleecker is the principal investigator for the SIROCCO trial and disclosed receiving research funding or consulting for AstraZeneca-MedImmune, Boehringer Ingelheim, Genentech/Roche, GlaxoSmithKline, Johnson & Johnson (Janssen), Merck, Novartis, Sanofi, Cephalon/Teva, and Regeneron-Sanofi. Dr. FitzGerald disclosed acting as an advisory board participant, receiving funding or fees, or both from AstraZeneca, ALK Abello, Boehringer Ingelheim, Hoffman-La Roche, Genentech, GlaxoSmithKline, MedImmune, Merck, Novartis, and Teva.
LONDON – The investigational treatment benralizumab significantly reduced the number of exacerbations that patients with severe, uncontrolled asthma experienced during the course of a year in two phase III studies.
In the SIROCCO and CALIMA trials, which altogether involved more than 2,000 adult patients, the annual exacerbation rate (AER) was cut by 28%-51%, compared with placebo when benralizumab was added to standard combination therapy of an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA).
Benralizumab treatment was also associated with significant improvements in lung function (up to 159 mL increase in FEV1), and reduced daily asthma symptoms of wheeze, cough, and dyspnea versus placebo. There were also improvements seen in patient-reported measures of asthma control and quality of life.
The results of these two multicenter, randomized, double-blind, placebo-controlled, parallel group studies were published in full online in The Lancet to coincide with their presentation at the annual congress of the European Respiratory Society.
Benralizumab is a humanized, monoclonal antibody that has been shown to rapidly and almost completely deplete the number of eosinophils in the blood, airways, and bone marrow, Eugene R Bleecker, MD, who presented the results of the SIROCCO study, explained at the meeting.
Dr. Bleecker, who is the director of the Center for Genomics and Personalized Medicine Research at Wake Forest University in Winston-Salem, N.C., observed that benralizumab “works a little bit differently” to other interleukin (IL)-5–targeting monoclonal antibodies, such as mepolizumab and reslizumab. Rather than target the IL-5 ligand itself, benralizumab binds to IL-5 receptors present on the surface of eosinophils. This action activates natural killer cells, which then destroy the eosinophils via antibody-dependent cell-mediated cytotoxicity.
Phase IIb data have already shown a benefit for benralizumab versus placebo in patients with uncontrolled asthma with high (300 cells/mcL or greater) eosinophil counts in the blood. The aim of the SIROCCO and CALIMA phase III trials was thus to examine the efficacy and safety of the novel agent further in this patient population.
In SIROCCO, 1,205 patients were randomized, and 1,306 were randomized in CALIMA. Key inclusion criteria were physician-diagnosed asthma requiring ICS/LABA therapy and at least two exacerbations in the past 12 months. Patients also needed to be symptomatic during a 4-week run-in period before being randomized to one of three study groups. The groups included one that received benralizumab at a subcutaneous dose of 30 mg every 4 weeks; another that received benralizumab at a subcutaneous dose of 30 mg every 4 weeks for the first three doses then a 30 mg dose or placebo injection alternating every 4 weeks; and a third group that received placebo injections every 4 weeks.
The mean age of patients in both studies and across treatment arms was broadly similar, ranging from 47 to 50 years. Around two thirds of the study population was female, with similar baseline characteristics.
The primary endpoint was the AER in patients with a blood eosinophil count of 300 cells/mcL or higher. In SIROCCO this was measured at 48 weeks and in CALIMA at 56 weeks. The respective AERs for placebo and for the 4- and 8-week dosing regimens of benralizumab were 1.33, 0.73, and 0.65 in SIROCCO and 0.93, 0.6, and 0.66 in CALIMA. This represented a 45% reduction in the AER for the 4-week and a 51% reduction for the 8-week regimens of benralizumab versus placebo in SIROCCO, and a 36% and 28% reduction, respectively, in CALIMA.
There was a large placebo effect and the overall population recruited into CALIMA may have had less severe asthma than the patients who participated in SIROCCO, the principal investigator for CALIMA, Mark FitzGerald, MD, pointed out during a press briefing organized by AstraZeneca. “But when you look at the composite of both studies together, you can see that the results are quite robust,” said Dr. FitzGerald, the director of the Centre for Lung and Heart Health at Vancouver Coastal Health Research Institute.
There was also some evidence that patients who had three or more prior exacerbations fared better, he said, highlighting the importance of defining the patient population who may benefit the most from this treatment.
Something that needs to be investigated further is why patients given the 8-week benralizumab regimen seemed to do better, at least numerically, than those given the 4-week regimen. Dr. FitzGerald suggested that “because eosinophil cells are such a powerful driver of disease, perhaps you may not actually need to be treated as frequently as historically we might have done.”
Other similar biologic agents need dosing every 2 to 4 weeks, but perhaps every 8 weeks is a possibility in the future for benralizumab. A lot can be learned from how biologics are used in rheumatology, he suggested, where treatments have started being given less frequently, because the biology of the various rheumatic diseases is now better understood.
Any adverse event was reported by a similar percentage of actively-treated (71%-75%) and placebo-treated (73%-78%) patients. The frequency and nature of other adverse events were similar to placebo.
The SIROCCO and CALIMA trial data will form part of AstraZeneca’s U.S. and EU regulatory submissions later this year for benralizumab as a treatment for severe, uncontrolled, eosinophilic asthma.
“Potentially, when it becomes available, benralizumab will provide a new therapeutic option for this class of patient.” Dr. FitzGerald said.
Benralizumab is also being investigated as a possible treatment for patients with less severe eosinophilic asthma in the BISE phase III study and as an option for those with severe chronic obstructive pulmonary disease who have high levels of eosinophils in the phase III VOYAGER program.
AstraZeneca and Kyowa Hakko Kirin funded the studies. Dr. Bleecker is the principal investigator for the SIROCCO trial and disclosed receiving research funding or consulting for AstraZeneca-MedImmune, Boehringer Ingelheim, Genentech/Roche, GlaxoSmithKline, Johnson & Johnson (Janssen), Merck, Novartis, Sanofi, Cephalon/Teva, and Regeneron-Sanofi. Dr. FitzGerald disclosed acting as an advisory board participant, receiving funding or fees, or both from AstraZeneca, ALK Abello, Boehringer Ingelheim, Hoffman-La Roche, Genentech, GlaxoSmithKline, MedImmune, Merck, Novartis, and Teva.
LONDON – The investigational treatment benralizumab significantly reduced the number of exacerbations that patients with severe, uncontrolled asthma experienced during the course of a year in two phase III studies.
In the SIROCCO and CALIMA trials, which altogether involved more than 2,000 adult patients, the annual exacerbation rate (AER) was cut by 28%-51%, compared with placebo when benralizumab was added to standard combination therapy of an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA).
Benralizumab treatment was also associated with significant improvements in lung function (up to 159 mL increase in FEV1), and reduced daily asthma symptoms of wheeze, cough, and dyspnea versus placebo. There were also improvements seen in patient-reported measures of asthma control and quality of life.
The results of these two multicenter, randomized, double-blind, placebo-controlled, parallel group studies were published in full online in The Lancet to coincide with their presentation at the annual congress of the European Respiratory Society.
Benralizumab is a humanized, monoclonal antibody that has been shown to rapidly and almost completely deplete the number of eosinophils in the blood, airways, and bone marrow, Eugene R Bleecker, MD, who presented the results of the SIROCCO study, explained at the meeting.
Dr. Bleecker, who is the director of the Center for Genomics and Personalized Medicine Research at Wake Forest University in Winston-Salem, N.C., observed that benralizumab “works a little bit differently” to other interleukin (IL)-5–targeting monoclonal antibodies, such as mepolizumab and reslizumab. Rather than target the IL-5 ligand itself, benralizumab binds to IL-5 receptors present on the surface of eosinophils. This action activates natural killer cells, which then destroy the eosinophils via antibody-dependent cell-mediated cytotoxicity.
Phase IIb data have already shown a benefit for benralizumab versus placebo in patients with uncontrolled asthma with high (300 cells/mcL or greater) eosinophil counts in the blood. The aim of the SIROCCO and CALIMA phase III trials was thus to examine the efficacy and safety of the novel agent further in this patient population.
In SIROCCO, 1,205 patients were randomized, and 1,306 were randomized in CALIMA. Key inclusion criteria were physician-diagnosed asthma requiring ICS/LABA therapy and at least two exacerbations in the past 12 months. Patients also needed to be symptomatic during a 4-week run-in period before being randomized to one of three study groups. The groups included one that received benralizumab at a subcutaneous dose of 30 mg every 4 weeks; another that received benralizumab at a subcutaneous dose of 30 mg every 4 weeks for the first three doses then a 30 mg dose or placebo injection alternating every 4 weeks; and a third group that received placebo injections every 4 weeks.
The mean age of patients in both studies and across treatment arms was broadly similar, ranging from 47 to 50 years. Around two thirds of the study population was female, with similar baseline characteristics.
The primary endpoint was the AER in patients with a blood eosinophil count of 300 cells/mcL or higher. In SIROCCO this was measured at 48 weeks and in CALIMA at 56 weeks. The respective AERs for placebo and for the 4- and 8-week dosing regimens of benralizumab were 1.33, 0.73, and 0.65 in SIROCCO and 0.93, 0.6, and 0.66 in CALIMA. This represented a 45% reduction in the AER for the 4-week and a 51% reduction for the 8-week regimens of benralizumab versus placebo in SIROCCO, and a 36% and 28% reduction, respectively, in CALIMA.
There was a large placebo effect and the overall population recruited into CALIMA may have had less severe asthma than the patients who participated in SIROCCO, the principal investigator for CALIMA, Mark FitzGerald, MD, pointed out during a press briefing organized by AstraZeneca. “But when you look at the composite of both studies together, you can see that the results are quite robust,” said Dr. FitzGerald, the director of the Centre for Lung and Heart Health at Vancouver Coastal Health Research Institute.
There was also some evidence that patients who had three or more prior exacerbations fared better, he said, highlighting the importance of defining the patient population who may benefit the most from this treatment.
Something that needs to be investigated further is why patients given the 8-week benralizumab regimen seemed to do better, at least numerically, than those given the 4-week regimen. Dr. FitzGerald suggested that “because eosinophil cells are such a powerful driver of disease, perhaps you may not actually need to be treated as frequently as historically we might have done.”
Other similar biologic agents need dosing every 2 to 4 weeks, but perhaps every 8 weeks is a possibility in the future for benralizumab. A lot can be learned from how biologics are used in rheumatology, he suggested, where treatments have started being given less frequently, because the biology of the various rheumatic diseases is now better understood.
Any adverse event was reported by a similar percentage of actively-treated (71%-75%) and placebo-treated (73%-78%) patients. The frequency and nature of other adverse events were similar to placebo.
The SIROCCO and CALIMA trial data will form part of AstraZeneca’s U.S. and EU regulatory submissions later this year for benralizumab as a treatment for severe, uncontrolled, eosinophilic asthma.
“Potentially, when it becomes available, benralizumab will provide a new therapeutic option for this class of patient.” Dr. FitzGerald said.
Benralizumab is also being investigated as a possible treatment for patients with less severe eosinophilic asthma in the BISE phase III study and as an option for those with severe chronic obstructive pulmonary disease who have high levels of eosinophils in the phase III VOYAGER program.
AstraZeneca and Kyowa Hakko Kirin funded the studies. Dr. Bleecker is the principal investigator for the SIROCCO trial and disclosed receiving research funding or consulting for AstraZeneca-MedImmune, Boehringer Ingelheim, Genentech/Roche, GlaxoSmithKline, Johnson & Johnson (Janssen), Merck, Novartis, Sanofi, Cephalon/Teva, and Regeneron-Sanofi. Dr. FitzGerald disclosed acting as an advisory board participant, receiving funding or fees, or both from AstraZeneca, ALK Abello, Boehringer Ingelheim, Hoffman-La Roche, Genentech, GlaxoSmithKline, MedImmune, Merck, Novartis, and Teva.
AT THE ERS CONGRESS 2016
Key clinical point: Benralizumab significantly reduced the annual exacerbation rate (AER), improved lung function, and reduced asthma symptoms.
Major finding: There was a 28%-51% decrease in the AER comparing (primary endpoint) two benralizumab regimens with placebo added to standard combination therapy.
Data source: Two randomized, double-blind, placebo-controlled, parallel group, phase III studies involving more than 2,000 adult patients with severe, uncontrolled, eosinophilic asthma.
Disclosures: AstraZeneca and Kyowa Hakko Kirin funded the studies. Dr. Bleecker is the principal investigator for the SIROCCO trial and disclosed receiving research funding or consulting for AstraZeneca-MedImmune, Boehringer Ingelheim, Genentech/Roche, GlaxoSmithKline, Johnson & Johnson (Jansen), Merck, Novartis, Sanofi, Cephalon/Teva, and Regeneron-Sanofi. Dr. FitzGerald is the principal investigator for the CALIMA trial. He disclosed acting as an advisory board participant, receiving funding or fees, or both from AstraZeneca, ALK Abello, Boehringer Ingelheim, Hoffman-La Roche, Genentech, GlaxoSmithKline, MedImmune, Merck, Novartis, and Teva.
Think outside the ‘cardiac box’ to predict cardiac injury
WAIKOLOA, HI. – For gunshot wounds, the current “cardiac box” was the poorest predictor of cardiac injury, results from a single-center retrospective study demonstrated.
“We determined that, from a statistical standpoint, the cardiac box should be redefined to include the area of the thorax that extends from the clavicle to xiphoid and from the anterior midline to the posterior midline of the left thorax,” Bryan C. Morse, MD, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “The classic cardiac box is inadequate to discriminate whether a gunshot wound will create a cardiac injury.”
Dr. Morse of Emory University and Grady Memorial Hospital, Atlanta, and his associates recently published their experience with penetrating cardiac injuries over the past 36 years and documented an increase in the number of cardiac injuries from gunshots over the past 10 years (J. Trauma Acute Care Surg. 2016 Jul 6. doi: 10.1097/TA.0000000000001165). They also noted that several of these injuries were caused by penetrating thoracic wounds outside the cardiac box.
The cardiac box is currently defined as the area of the chest overlying the heart, bounded by the midclavicular lines (laterally) and from the clavicles to the tip of the xiphoid. “Surgical teaching dictates that penetrating injuries (i.e. stab wounds and gunshot wounds) in the box have the highest likelihood of cardiac injury and thereby mandate further evaluation,” Dr. Morse said. “These studies, however, are based on small patient sample sizes in which the majority were stab wound victims and underwent minimal statistical scrutiny.”
In what he said is the largest study of its kind, Dr. Morse and his associates conducted a retrospective review of trauma registry data from Grady’s trauma center and autopsy reports to identify patients with penetrating thoracic gunshot wounds and cardiac injury from 2011 to 2013 and to evaluate the relationship between penetrating injuries and the likelihood of a cardiac injury. Using a circumferential grid system around the thorax, the researchers employed logistic regression analysis to compare differences in rates of cardiac injury from entrance/exit wounds in the cardiac box, versus outside the box. They repeated the process to identify potential regions that yield improved predictions for cardiac injury over the current definition of the cardiac box.
Over the 3-year study period, 263 patients sustained 735 penetrating thoracic wounds, of which 80% were gunshot wounds (GSWs). Most of the patients were males (89%) with a median of two injuries each. After stab wounds were excluded, 277 GSWs to the thorax were included for study and 95 (34%) injured the heart. Of the 233 GSWs entering the cardiac box, 30% caused cardiac injury while, of the 44 GSWs outside the cardiac box, 32% penetrated the heart, suggesting that the current cardiac box is a poor predictor of cardiac injury relative to the thoracic non–cardiac box regions (OR 1.1; P = .71).
The researchers observed that the regions from the anterior to the posterior midline of the left thorax provided the highest positive predictive value, with a sensitivity of 90% and a specificity of 31%, making this region the most statistically significant discriminator of cardiac injury (OR, 4.4; P less than .01). This finding was primarily based on the fact that gunshots to the left lateral chest (an area not currently included in the box) had a high rate of cardiac injury (41%; OR, 1.4).
“The current cardiac box is unable to discriminate between gunshot wounds that will cause a cardiac injury and those that will not,” Dr. Morse said. “Any gunshot wound to the chest can cause a cardiac injury. While clinically relevant box borders would include the left chest, the bottom line for surgeons is to think outside the current cardiac box.”
The improved cardiac box that he and his associates proposed includes the area from the clavicles to the xiphoid and from the anterior to the posterior midline over the left thorax. “While this may be intuitive, it is not what we as surgeons have been teaching,” he said. “Finally, gunshots to areas such as the right posterior and posterolateral chest were associated with rates of cardiac injury greater than 30% despite their distance from the heart. This led us to conclude that a gunshot anywhere to the chest should be considered to potentially cause a cardiac injury.”
Dr. Morse acknowledged certain limitations of the study, including the fact that the study excluded graze wounds and gunshots above the clavicles and below the xiphoid. “However, a small percentage of these did cause cardiac injuries, which emphasizes the point that gunshot wounds from any entrance can cause cardiac injury.”
Invited discussant Nicholas Namias, MD, professor and chief of the division of acute care surgery at Jackson Memorial Hospital, Miami, said that the study by Dr. Morse and his associates “confirms what Dr. [Grace] Rozycki showed 20 years ago: Forget the [cardiac] box; it’s dead. Just throw an ultrasound probe on.”
Dr. Morse reported having no relevant financial disclosures.
WAIKOLOA, HI. – For gunshot wounds, the current “cardiac box” was the poorest predictor of cardiac injury, results from a single-center retrospective study demonstrated.
“We determined that, from a statistical standpoint, the cardiac box should be redefined to include the area of the thorax that extends from the clavicle to xiphoid and from the anterior midline to the posterior midline of the left thorax,” Bryan C. Morse, MD, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “The classic cardiac box is inadequate to discriminate whether a gunshot wound will create a cardiac injury.”
Dr. Morse of Emory University and Grady Memorial Hospital, Atlanta, and his associates recently published their experience with penetrating cardiac injuries over the past 36 years and documented an increase in the number of cardiac injuries from gunshots over the past 10 years (J. Trauma Acute Care Surg. 2016 Jul 6. doi: 10.1097/TA.0000000000001165). They also noted that several of these injuries were caused by penetrating thoracic wounds outside the cardiac box.
The cardiac box is currently defined as the area of the chest overlying the heart, bounded by the midclavicular lines (laterally) and from the clavicles to the tip of the xiphoid. “Surgical teaching dictates that penetrating injuries (i.e. stab wounds and gunshot wounds) in the box have the highest likelihood of cardiac injury and thereby mandate further evaluation,” Dr. Morse said. “These studies, however, are based on small patient sample sizes in which the majority were stab wound victims and underwent minimal statistical scrutiny.”
In what he said is the largest study of its kind, Dr. Morse and his associates conducted a retrospective review of trauma registry data from Grady’s trauma center and autopsy reports to identify patients with penetrating thoracic gunshot wounds and cardiac injury from 2011 to 2013 and to evaluate the relationship between penetrating injuries and the likelihood of a cardiac injury. Using a circumferential grid system around the thorax, the researchers employed logistic regression analysis to compare differences in rates of cardiac injury from entrance/exit wounds in the cardiac box, versus outside the box. They repeated the process to identify potential regions that yield improved predictions for cardiac injury over the current definition of the cardiac box.
Over the 3-year study period, 263 patients sustained 735 penetrating thoracic wounds, of which 80% were gunshot wounds (GSWs). Most of the patients were males (89%) with a median of two injuries each. After stab wounds were excluded, 277 GSWs to the thorax were included for study and 95 (34%) injured the heart. Of the 233 GSWs entering the cardiac box, 30% caused cardiac injury while, of the 44 GSWs outside the cardiac box, 32% penetrated the heart, suggesting that the current cardiac box is a poor predictor of cardiac injury relative to the thoracic non–cardiac box regions (OR 1.1; P = .71).
The researchers observed that the regions from the anterior to the posterior midline of the left thorax provided the highest positive predictive value, with a sensitivity of 90% and a specificity of 31%, making this region the most statistically significant discriminator of cardiac injury (OR, 4.4; P less than .01). This finding was primarily based on the fact that gunshots to the left lateral chest (an area not currently included in the box) had a high rate of cardiac injury (41%; OR, 1.4).
“The current cardiac box is unable to discriminate between gunshot wounds that will cause a cardiac injury and those that will not,” Dr. Morse said. “Any gunshot wound to the chest can cause a cardiac injury. While clinically relevant box borders would include the left chest, the bottom line for surgeons is to think outside the current cardiac box.”
The improved cardiac box that he and his associates proposed includes the area from the clavicles to the xiphoid and from the anterior to the posterior midline over the left thorax. “While this may be intuitive, it is not what we as surgeons have been teaching,” he said. “Finally, gunshots to areas such as the right posterior and posterolateral chest were associated with rates of cardiac injury greater than 30% despite their distance from the heart. This led us to conclude that a gunshot anywhere to the chest should be considered to potentially cause a cardiac injury.”
Dr. Morse acknowledged certain limitations of the study, including the fact that the study excluded graze wounds and gunshots above the clavicles and below the xiphoid. “However, a small percentage of these did cause cardiac injuries, which emphasizes the point that gunshot wounds from any entrance can cause cardiac injury.”
Invited discussant Nicholas Namias, MD, professor and chief of the division of acute care surgery at Jackson Memorial Hospital, Miami, said that the study by Dr. Morse and his associates “confirms what Dr. [Grace] Rozycki showed 20 years ago: Forget the [cardiac] box; it’s dead. Just throw an ultrasound probe on.”
Dr. Morse reported having no relevant financial disclosures.
WAIKOLOA, HI. – For gunshot wounds, the current “cardiac box” was the poorest predictor of cardiac injury, results from a single-center retrospective study demonstrated.
“We determined that, from a statistical standpoint, the cardiac box should be redefined to include the area of the thorax that extends from the clavicle to xiphoid and from the anterior midline to the posterior midline of the left thorax,” Bryan C. Morse, MD, said in an interview in advance of the annual meeting of the American Association for the Surgery of Trauma. “The classic cardiac box is inadequate to discriminate whether a gunshot wound will create a cardiac injury.”
Dr. Morse of Emory University and Grady Memorial Hospital, Atlanta, and his associates recently published their experience with penetrating cardiac injuries over the past 36 years and documented an increase in the number of cardiac injuries from gunshots over the past 10 years (J. Trauma Acute Care Surg. 2016 Jul 6. doi: 10.1097/TA.0000000000001165). They also noted that several of these injuries were caused by penetrating thoracic wounds outside the cardiac box.
The cardiac box is currently defined as the area of the chest overlying the heart, bounded by the midclavicular lines (laterally) and from the clavicles to the tip of the xiphoid. “Surgical teaching dictates that penetrating injuries (i.e. stab wounds and gunshot wounds) in the box have the highest likelihood of cardiac injury and thereby mandate further evaluation,” Dr. Morse said. “These studies, however, are based on small patient sample sizes in which the majority were stab wound victims and underwent minimal statistical scrutiny.”
In what he said is the largest study of its kind, Dr. Morse and his associates conducted a retrospective review of trauma registry data from Grady’s trauma center and autopsy reports to identify patients with penetrating thoracic gunshot wounds and cardiac injury from 2011 to 2013 and to evaluate the relationship between penetrating injuries and the likelihood of a cardiac injury. Using a circumferential grid system around the thorax, the researchers employed logistic regression analysis to compare differences in rates of cardiac injury from entrance/exit wounds in the cardiac box, versus outside the box. They repeated the process to identify potential regions that yield improved predictions for cardiac injury over the current definition of the cardiac box.
Over the 3-year study period, 263 patients sustained 735 penetrating thoracic wounds, of which 80% were gunshot wounds (GSWs). Most of the patients were males (89%) with a median of two injuries each. After stab wounds were excluded, 277 GSWs to the thorax were included for study and 95 (34%) injured the heart. Of the 233 GSWs entering the cardiac box, 30% caused cardiac injury while, of the 44 GSWs outside the cardiac box, 32% penetrated the heart, suggesting that the current cardiac box is a poor predictor of cardiac injury relative to the thoracic non–cardiac box regions (OR 1.1; P = .71).
The researchers observed that the regions from the anterior to the posterior midline of the left thorax provided the highest positive predictive value, with a sensitivity of 90% and a specificity of 31%, making this region the most statistically significant discriminator of cardiac injury (OR, 4.4; P less than .01). This finding was primarily based on the fact that gunshots to the left lateral chest (an area not currently included in the box) had a high rate of cardiac injury (41%; OR, 1.4).
“The current cardiac box is unable to discriminate between gunshot wounds that will cause a cardiac injury and those that will not,” Dr. Morse said. “Any gunshot wound to the chest can cause a cardiac injury. While clinically relevant box borders would include the left chest, the bottom line for surgeons is to think outside the current cardiac box.”
The improved cardiac box that he and his associates proposed includes the area from the clavicles to the xiphoid and from the anterior to the posterior midline over the left thorax. “While this may be intuitive, it is not what we as surgeons have been teaching,” he said. “Finally, gunshots to areas such as the right posterior and posterolateral chest were associated with rates of cardiac injury greater than 30% despite their distance from the heart. This led us to conclude that a gunshot anywhere to the chest should be considered to potentially cause a cardiac injury.”
Dr. Morse acknowledged certain limitations of the study, including the fact that the study excluded graze wounds and gunshots above the clavicles and below the xiphoid. “However, a small percentage of these did cause cardiac injuries, which emphasizes the point that gunshot wounds from any entrance can cause cardiac injury.”
Invited discussant Nicholas Namias, MD, professor and chief of the division of acute care surgery at Jackson Memorial Hospital, Miami, said that the study by Dr. Morse and his associates “confirms what Dr. [Grace] Rozycki showed 20 years ago: Forget the [cardiac] box; it’s dead. Just throw an ultrasound probe on.”
Dr. Morse reported having no relevant financial disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point: The current cardiac box is inadequate to discriminate whether a gunshot wound will create a cardiac injury.
Major finding: Of the 233 gunshot wounds entering the cardiac box, 30% caused cardiac injury while, of the 44 GSWs outside the cardiac box, 32% penetrated the heart, suggesting that the current cardiac box is a poor predictor of cardiac injury relative to the thoracic non–cardiac box regions (OR 1.1; P = .71).
Data source: A retrospective review of 236 patients with penetrating thoracic gunshot wounds and cardiac injury from 2011 to 2013.
Disclosures: Dr. Morse reported having no relevant financial disclosures.
Should I throw out my expired medications?
A 55-year-old patient requests new prescriptions at a routine appointment. She will be traveling internationally next month and wants to replace her emergency medication kit, as the medications in it (ciprofloxacin, loperamide, and oxycodone) have all expired.
What do you do?
A) Replace the prescription for ciprofloxacin.
B) Replace all three medications.
C) Tell the patient that all the meds should still be fine.
This is a common concern brought up by patients. Many patients discard medications when they pass the expiration date on the package. Is this necessary? Is there a health risk to taking expired medications, and is it okay from a therapeutic standpoint to use medications past their expiration date?
The expiration date is not a date that the drug stops being effective or potentially becomes toxic. It is a date, required by law, that the manufacturer can guarantee greater than 90% original potency of the medication. There really isn’t incentive for pharmaceutical companies to extend the expiration dates, as it is profitable for patients to throw away expired medications and replace them with new prescriptions.
The U.S. military purchases a large stockpile of drugs and has the potential for having a great deal of expired medications. To help reduce this problem, the Food and Drug Administration administers the shelf-life extension program (SLEP) for the U.S. military as a testing and evaluation program designed to justify an extension of the shelf life of stockpiled drug products.1
Robbe Lyon, MD, and colleagues reported data from the SLEP.2 A total of 122 drugs were studied representing 3,005 lots, with 88% of these extended at least 1 year past the expiration date, with an average extension of more than 5 years. Several antibiotics were studied, including ciprofloxacin (mean extension, 55 months), amoxicillin (mean extension, 23 months), and doxycycline (mean extension, 50 months).
Lee Cantrell, PharmD, and coinvestigators looked at sealed drugs from a retail pharmacy that were 28-40 years past their expiration date.3 Amazingly, 12 of the 14 compounds tested were in concentrations that were at least 90% of the labeled amount. Among the drugs that were tested that maintained greater than 90% of the labeled amount were acetaminophen, codeine, hydrocodone, and barbiturates. Aspirin and amphetamine were the two drugs that did not have greater than 90% of the labeled amount. The aspirin amounts were very low, about 1% of the listed amount on the package.
The major myth surrounding expired medications is that taking an expired medication could be toxic.
There is one case report of toxicity from the use of expired tetracycline.4 This was a case series of three patients who developed reversible Fanconi syndrome linked to using an expired tetracycline preparation. That preparation of tetracycline is no longer available.
There are no other reports of toxicity due to use of expired medications.5,6 There appears to be no direct risk of toxicity to the patient by using medication past the expiration date.
The risk that isn’t answered is the risk of using medications that may not be effective if potency isn’t guaranteed beyond the expiration date. It appears that most drugs are effective for years past the expiration date.
This isn’t an issue for medications for treatment of chronic conditions, as patients take the medications every day, and the medications will be used up long before they expire. For medications that are used infrequently – analgesics, antihistamines, and medications for traveler’s diarrhea – they appear to be stable for years past expiration, and there is little risk to the patient if the medications are not fully effective.
I think aspirin should not be used past expiration, given the data showing that it breaks down more so than other medications. For the case at the start of this article, I think having the patient use the expired medications should be fine.
References
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
A 55-year-old patient requests new prescriptions at a routine appointment. She will be traveling internationally next month and wants to replace her emergency medication kit, as the medications in it (ciprofloxacin, loperamide, and oxycodone) have all expired.
What do you do?
A) Replace the prescription for ciprofloxacin.
B) Replace all three medications.
C) Tell the patient that all the meds should still be fine.
This is a common concern brought up by patients. Many patients discard medications when they pass the expiration date on the package. Is this necessary? Is there a health risk to taking expired medications, and is it okay from a therapeutic standpoint to use medications past their expiration date?
The expiration date is not a date that the drug stops being effective or potentially becomes toxic. It is a date, required by law, that the manufacturer can guarantee greater than 90% original potency of the medication. There really isn’t incentive for pharmaceutical companies to extend the expiration dates, as it is profitable for patients to throw away expired medications and replace them with new prescriptions.
The U.S. military purchases a large stockpile of drugs and has the potential for having a great deal of expired medications. To help reduce this problem, the Food and Drug Administration administers the shelf-life extension program (SLEP) for the U.S. military as a testing and evaluation program designed to justify an extension of the shelf life of stockpiled drug products.1
Robbe Lyon, MD, and colleagues reported data from the SLEP.2 A total of 122 drugs were studied representing 3,005 lots, with 88% of these extended at least 1 year past the expiration date, with an average extension of more than 5 years. Several antibiotics were studied, including ciprofloxacin (mean extension, 55 months), amoxicillin (mean extension, 23 months), and doxycycline (mean extension, 50 months).
Lee Cantrell, PharmD, and coinvestigators looked at sealed drugs from a retail pharmacy that were 28-40 years past their expiration date.3 Amazingly, 12 of the 14 compounds tested were in concentrations that were at least 90% of the labeled amount. Among the drugs that were tested that maintained greater than 90% of the labeled amount were acetaminophen, codeine, hydrocodone, and barbiturates. Aspirin and amphetamine were the two drugs that did not have greater than 90% of the labeled amount. The aspirin amounts were very low, about 1% of the listed amount on the package.
The major myth surrounding expired medications is that taking an expired medication could be toxic.
There is one case report of toxicity from the use of expired tetracycline.4 This was a case series of three patients who developed reversible Fanconi syndrome linked to using an expired tetracycline preparation. That preparation of tetracycline is no longer available.
There are no other reports of toxicity due to use of expired medications.5,6 There appears to be no direct risk of toxicity to the patient by using medication past the expiration date.
The risk that isn’t answered is the risk of using medications that may not be effective if potency isn’t guaranteed beyond the expiration date. It appears that most drugs are effective for years past the expiration date.
This isn’t an issue for medications for treatment of chronic conditions, as patients take the medications every day, and the medications will be used up long before they expire. For medications that are used infrequently – analgesics, antihistamines, and medications for traveler’s diarrhea – they appear to be stable for years past expiration, and there is little risk to the patient if the medications are not fully effective.
I think aspirin should not be used past expiration, given the data showing that it breaks down more so than other medications. For the case at the start of this article, I think having the patient use the expired medications should be fine.
References
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
A 55-year-old patient requests new prescriptions at a routine appointment. She will be traveling internationally next month and wants to replace her emergency medication kit, as the medications in it (ciprofloxacin, loperamide, and oxycodone) have all expired.
What do you do?
A) Replace the prescription for ciprofloxacin.
B) Replace all three medications.
C) Tell the patient that all the meds should still be fine.
This is a common concern brought up by patients. Many patients discard medications when they pass the expiration date on the package. Is this necessary? Is there a health risk to taking expired medications, and is it okay from a therapeutic standpoint to use medications past their expiration date?
The expiration date is not a date that the drug stops being effective or potentially becomes toxic. It is a date, required by law, that the manufacturer can guarantee greater than 90% original potency of the medication. There really isn’t incentive for pharmaceutical companies to extend the expiration dates, as it is profitable for patients to throw away expired medications and replace them with new prescriptions.
The U.S. military purchases a large stockpile of drugs and has the potential for having a great deal of expired medications. To help reduce this problem, the Food and Drug Administration administers the shelf-life extension program (SLEP) for the U.S. military as a testing and evaluation program designed to justify an extension of the shelf life of stockpiled drug products.1
Robbe Lyon, MD, and colleagues reported data from the SLEP.2 A total of 122 drugs were studied representing 3,005 lots, with 88% of these extended at least 1 year past the expiration date, with an average extension of more than 5 years. Several antibiotics were studied, including ciprofloxacin (mean extension, 55 months), amoxicillin (mean extension, 23 months), and doxycycline (mean extension, 50 months).
Lee Cantrell, PharmD, and coinvestigators looked at sealed drugs from a retail pharmacy that were 28-40 years past their expiration date.3 Amazingly, 12 of the 14 compounds tested were in concentrations that were at least 90% of the labeled amount. Among the drugs that were tested that maintained greater than 90% of the labeled amount were acetaminophen, codeine, hydrocodone, and barbiturates. Aspirin and amphetamine were the two drugs that did not have greater than 90% of the labeled amount. The aspirin amounts were very low, about 1% of the listed amount on the package.
The major myth surrounding expired medications is that taking an expired medication could be toxic.
There is one case report of toxicity from the use of expired tetracycline.4 This was a case series of three patients who developed reversible Fanconi syndrome linked to using an expired tetracycline preparation. That preparation of tetracycline is no longer available.
There are no other reports of toxicity due to use of expired medications.5,6 There appears to be no direct risk of toxicity to the patient by using medication past the expiration date.
The risk that isn’t answered is the risk of using medications that may not be effective if potency isn’t guaranteed beyond the expiration date. It appears that most drugs are effective for years past the expiration date.
This isn’t an issue for medications for treatment of chronic conditions, as patients take the medications every day, and the medications will be used up long before they expire. For medications that are used infrequently – analgesics, antihistamines, and medications for traveler’s diarrhea – they appear to be stable for years past expiration, and there is little risk to the patient if the medications are not fully effective.
I think aspirin should not be used past expiration, given the data showing that it breaks down more so than other medications. For the case at the start of this article, I think having the patient use the expired medications should be fine.
References
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
Checklist may prompt cuts in unneeded antibiotic prescriptions
Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.
The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).
The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).
Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).
“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.
These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.
Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).
Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.
“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).
Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.
There are few efficacious interventions for respiratory tract infection available to primary care clinicians beyond offering reassurance and self-management advice, so the modest benefit offered by antibiotics can persuade general practitioners to prescribe them.
To derive (and validate) a clinical prediction rule to improve targeted antibiotic prescribing in children with respiratory tract infections, Hay et al determined the seven characteristics independently associated (P less than .01 for all associations) with hospital admission for children presenting to primary care physicians with cough and respiratory tract infection (STARWAVe). Using this seven-item checklist to help structure point-of-care assessment for this patient population should predict the risk of hospital admission with remarkable accuracy (area under the received operating characteristic curve, 0.81; 95% CI, 0.76-0.85).
STARWAVe offers primary care clinicians an evidence-based practical tool to help guide antibiotic prescription decisions and, through shared decision-making, has the potential to reduce antibiotic prescription based on prognostic uncertainty or on nonmedical grounds.
If STARWAVe leads to an increase in antibiotic prescription (to 90%) in high-risk children and a parallel halving of prescription to those at low risk of hospital admission, it could achieve a 10% overall reduction in primary care antibiotic prescriptions for respiratory tract infections.
These comments are excerpted from a commentary by Dr. Christopher C. Winchester from Oxford PharmaGenesis and Durham University (England), Alison Chisholm, MSc, from the Respiratory Effectiveness Group in Cambridge (England), and Dr. David Price from the University of Aberdeen (Scotland) and the Observational and Pragmatic Research Institute in Singapore. Dr. Winchester and Dr. Price disclosed financial relationships with numerous industry sources; Ms. Chisholm indicated no financial relationships relevant to this article. Funded information was not provided. (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30272-7).
There are few efficacious interventions for respiratory tract infection available to primary care clinicians beyond offering reassurance and self-management advice, so the modest benefit offered by antibiotics can persuade general practitioners to prescribe them.
To derive (and validate) a clinical prediction rule to improve targeted antibiotic prescribing in children with respiratory tract infections, Hay et al determined the seven characteristics independently associated (P less than .01 for all associations) with hospital admission for children presenting to primary care physicians with cough and respiratory tract infection (STARWAVe). Using this seven-item checklist to help structure point-of-care assessment for this patient population should predict the risk of hospital admission with remarkable accuracy (area under the received operating characteristic curve, 0.81; 95% CI, 0.76-0.85).
STARWAVe offers primary care clinicians an evidence-based practical tool to help guide antibiotic prescription decisions and, through shared decision-making, has the potential to reduce antibiotic prescription based on prognostic uncertainty or on nonmedical grounds.
If STARWAVe leads to an increase in antibiotic prescription (to 90%) in high-risk children and a parallel halving of prescription to those at low risk of hospital admission, it could achieve a 10% overall reduction in primary care antibiotic prescriptions for respiratory tract infections.
These comments are excerpted from a commentary by Dr. Christopher C. Winchester from Oxford PharmaGenesis and Durham University (England), Alison Chisholm, MSc, from the Respiratory Effectiveness Group in Cambridge (England), and Dr. David Price from the University of Aberdeen (Scotland) and the Observational and Pragmatic Research Institute in Singapore. Dr. Winchester and Dr. Price disclosed financial relationships with numerous industry sources; Ms. Chisholm indicated no financial relationships relevant to this article. Funded information was not provided. (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30272-7).
There are few efficacious interventions for respiratory tract infection available to primary care clinicians beyond offering reassurance and self-management advice, so the modest benefit offered by antibiotics can persuade general practitioners to prescribe them.
To derive (and validate) a clinical prediction rule to improve targeted antibiotic prescribing in children with respiratory tract infections, Hay et al determined the seven characteristics independently associated (P less than .01 for all associations) with hospital admission for children presenting to primary care physicians with cough and respiratory tract infection (STARWAVe). Using this seven-item checklist to help structure point-of-care assessment for this patient population should predict the risk of hospital admission with remarkable accuracy (area under the received operating characteristic curve, 0.81; 95% CI, 0.76-0.85).
STARWAVe offers primary care clinicians an evidence-based practical tool to help guide antibiotic prescription decisions and, through shared decision-making, has the potential to reduce antibiotic prescription based on prognostic uncertainty or on nonmedical grounds.
If STARWAVe leads to an increase in antibiotic prescription (to 90%) in high-risk children and a parallel halving of prescription to those at low risk of hospital admission, it could achieve a 10% overall reduction in primary care antibiotic prescriptions for respiratory tract infections.
These comments are excerpted from a commentary by Dr. Christopher C. Winchester from Oxford PharmaGenesis and Durham University (England), Alison Chisholm, MSc, from the Respiratory Effectiveness Group in Cambridge (England), and Dr. David Price from the University of Aberdeen (Scotland) and the Observational and Pragmatic Research Institute in Singapore. Dr. Winchester and Dr. Price disclosed financial relationships with numerous industry sources; Ms. Chisholm indicated no financial relationships relevant to this article. Funded information was not provided. (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30272-7).
Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.
The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).
The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).
Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).
“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.
These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.
Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).
Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.
“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).
Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.
Primary care practitioners’ use of a seven-item checklist may reduce the number of pediatric patients with respiratory tract infections who are prescribed unnecessary antibiotics, a prognostic cohort study suggests.
The study revealed short illness (a duration of illness of 3 days or less), temperature (a body temperature of 37.8°C or greater at presentation), age (being under 2 years), intercostal or subcostal recession, wheeze on auscultation, asthma, and vomiting (moderate or severe in the previous 24 hours) were each independently associated with hospital admission (P less than .01 for all associations).
The checklist includes these seven characteristics or risk variables (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]). To use the checklist, a primary care practitioner would assign one point for the presence of each item in a patient then add up all of the points to determine that patient’s risk level for future hospital admission for respiratory tract infection. A score of 1 point or less, observed in 5,593 (67%) cases would be considered indicative of a very low rate of risk for hospitalization (0.3%, 0.2%-0.4%). A score of 2 or 3 points, found for 2,520 (30%) children, would be considered as a normal level of risk (1.5%, 1.0%-1.9%), and a score of 4 or more points, seen in 204 (3%) children, would signify a high risk level (11.8%, 7.3%-16.2%).
Of the 8,394 children assessed, 78 (0.9%; 95% confidence interval, 0.7%-1.2%) were admitted to a hospital. Most were admitted on days 2-7 (33, 42%) and on days 8-30 (30, 39%) following recruitment. Only 15 (19%) were admitted on the day of recruitment (day 1).
“Many clinicians report that they prescribe antibiotics just in case, to mitigate perceived risk of future hospital admission and complications, and that failing to provide a prescription for a child who subsequently becomes seriously unwell is professionally unacceptable. If primary care clinicians could identify children at low (or very low) risk of such future complications, the reduced clinical uncertainty could lead to a reduced use of antibiotics in these groups of patients,” wrote first author Alastair Hay, MD, from the Centre for Academic Primary Care in the School of Social and Community Medicine at the University of Bristol (England), and his colleagues.
These researchers conducted the study based on a structured, blinded review of the medical records from children aged between 3 months and 16 years presenting with acute cough (less than or equal to 28 days) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013. The primary study outcome was hospital admission for respiratory tract infection within 30 days.
Additionally, a multivariable model was employed to detect factors associated with increased risk of hospital admission. As measured by receiver operating characteristic curve analysis, the accuracy of the STARWAVe score checklist in predicting risk groups and associated risk of hospitalization was found to be high (0.81; 95% CI, 0.77-0.86). The suggested probability of hospital admission for children who did not have any of the seven characteristics included in the checklist was found to be exceptionally low (0.14%).
Significantly associated parent-reported variables included both moderate or severe vomiting and severe fever, each in the previous 24 hours. Significant clinician-reported variables included intercostal or subcostal recession and wheeze on auscultation.
“The main value of our results is to reduce clinical uncertainty and antibiotic use in children least likely to benefit from them, namely those at very low risk of future hospital admission,” Dr. Hay and his associates noted in The Lancet Respiratory Medicine (Lancet Respir Med. 2016 Sep 1. doi: 10.1016/S2213-2600(16)30223-5).
Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only one of the study’s authors, Dr. Peter Muir, reported ties to industry sources.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: Use of a checklist of seven characteristics independently associated with hospital admission for children presenting to primary care physicians with cough and respiratory tract infection may lead to more appropriate prescribing of antibiotics in this patient population.
Major finding: Only 0.9% of 8,394 pediatric patients presenting to primary care with acute cough and respiratory tract infections were admitted to hospitals. A checklist based on seven characteristics observed in study participants (short illness, temperature, age, recession, wheeze, asthma, and vomiting [mnemonic STARWAVe]) that were independently associated with hospital admission (P less than .01 for all associations) was developed to define three risk categories for future hospital admission for respiratory tract infection.
Data sources: A prognostic cohort study of children aged between 3 months and 16 years presenting with acute cough (28 days or fewer) and respiratory tract infection treated by 519 general practitioners in 247 practices in England between July 2011 and June 2013.
Disclosures: Funding for this study was provided by the National Institute for Health Research and sponsored by the University of Bristol. Only Dr. Peter Muir reported ties to industry sources.
