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Cardiac biomarkers refine antihypertensive drug initiation decisions
PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.
That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.
Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.
Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.
“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.
He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
The results
Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.
Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.
Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.
The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.
Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.
In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.
“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.
One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.
“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.
Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141
PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.
That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.
Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.
Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.
“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.
He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
The results
Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.
Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.
Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.
The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.
Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.
In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.
“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.
One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.
“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.
Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141
PHILADELPHIA – Incorporation of cardiac biomarkers into current guideline-based decision-making regarding initiation of antihypertensive medication in patients with previously untreated mild or moderate high blood pressure leads to more appropriate and selective matching of intensive blood pressure control with true patient risk, Ambarish Pandey, MD, reported at the American Heart Association scientific sessions.
That’s because the 2017 American College of Cardiology/AHA blood pressure guidelines recommend incorporating the ACC/AHA 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk Calculator into decision making as to whether to start antihypertensive drug therapy in patients with stage 1 hypertension (130-139/80-89 mm Hg), but the risk calculator doesn’t account for the risk of heart failure.
Yet by far the greatest benefit of intensive BP lowering is in reducing the risk of developing heart failure, as demonstrated in the landmark SPRINT trial, which showed that intensive BP lowering achieved much greater risk reduction in new-onset heart failure than in atherosclerotic cardiovascular events.
Thus, there’s a need for better strategies to guide antihypertensive therapy. And therein lies the rationale for incorporating into the risk assessment an individual’s values for N-terminal pro–brain natriuretic peptide (NT-proBNP), which reflects chronic myocardial stress, and high-sensitivity cardiac troponin T (hs-cTnT), which when elevated signals myocardial injury.
“Cardiac biomarkers are intermediate phenotypes from hypertension to future cardiovascular events. They can identify individuals at increased risk for atherosclerotic events, and at even higher risk for heart failure events,” explained Dr. Pandey, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.
He presented a study of 12,987 participants in three major U.S. cohort studies: the Atherosclerosis Risk In Communities (ARIC) study, the Multi-Ethnic Study of Atherosclerosis (MESA), and the Dallas Heart Study. At baseline, none of the participants were on antihypertensive therapy or had known cardiovascular disease. During 10 years of prospective follow-up, 825 of them experienced a first cardiovascular disease event: 251 developed heart failure and 574 had an MI, stroke, or cardiovascular death. Dr. Pandey and his coworkers calculated the cardiovascular event incidence rate and number-needed-to-treat with intensive antihypertensive drug therapy to prevent a first cardiovascular disease event on the basis of whether patients in the various BP categories were positive or negative for one or more biomarkers.
The results
Fifty-four percent of subjects had normal BP, defined in the guidelines as less than 120/80 mm Hg. Another 3% had BP in excess of 160/100 mm Hg. No controversy exists regarding pharmacotherapy in either of these groups: It’s not warranted in the former, essential in the latter.
Another 3,000 individuals had what the ACC/AHA guidelines define as elevated BP, meaning 120-129/<80 mm Hg, or low-risk stage 1 hypertension of 130-139/80-89 mm Hg and a 10-year ASCVD risk score of less than 10%. Initiation of antihypertensive medication in these groups is not recommended in the guidelines. Yet 36% of these individuals had at least one positive cardiac biomarker. And here’s the eye-opening finding: Notably, the 10-year cardiovascular event incidence rate in this biomarker group not currently recommended for antihypertensive pharmacotherapy was 11%, more than double the 4.6% rate in the biomarker-negative group, which in turn was comparable to the 3.8% in the normal BP participants.
Antihypertensive therapy was recommended according to the guidelines in 20% of the total study population, comprising patients with stage 1 hypertension who had an ASCVD risk score of 10% or more as well as those with stage 2 hypertension, defined as BP greater than 140/90 mm Hg but less than 160/100 mm Hg. Forty-eight percent of these subjects were positive for at least one biomarker. Their cardiovascular incidence rate was 15.1%, compared to the 7.9% rate in biomarker-negative individuals.
The estimated number-needed-to-treat (NNT) with intensive blood pressure–lowering therapy to a target systolic BP of less than 120 mm Hg, as in SPRINT, to prevent one cardiovascular event in individuals not currently guideline-recommended for antihypertensive medications was 86 in those who were biomarker-negative. The NNT dropped to 36 in the biomarker-positive subgroup, a far more attractive figure that suggests a reasonable likelihood of benefit from intensive blood pressure control, in Dr. Pandey’s view.
Similarly, among individuals currently recommended for pharmacotherapy initiation, the NNTs were 49 if biomarker-negative, improving to 26 in those positive for one or both biomarkers, which was comparable to the NNT of 22 in the group with blood pressures greater than 160/100 mm Hg. The NNT of 49 in the biomarker-negative subgroup is in a borderline gray zone warranting individualized shared decision-making regarding pharmacotherapy, Dr. Pandey said.
In this study, an elevated hs-cTnT was defined as 6 ng/L or more, while an elevated NT-proBNP was considered to be at least 100 pg/mL.
“It’s noteworthy that the degree of elevation in hs-cTnT and NT-proBNP which were observed in our study were pretty subtle and much below the threshold used for diagnosis of ischemic events or heart failure. Thus, these elevations were largely representative of subtle chronic injury and not acute events,” according to the cardiologist.
One audience member asked if the elevated biomarkers could simply be a surrogate for longer duration of exposure of the heart to high BP. Sure, Dr. Pandey replied, pointing to the 6-year greater average age of the biomarker-positive participants.
“It is likely that biomarker-positive status is capturing the culmination of longstanding exposure. But the thing about hypertension is there are no symptoms that can signal to the patient or the doctor that they have this disease, so testing for the biomarkers can actually capture the high-risk group that may have had hypertension for a long duration but now needs to be treated in order to prevent the advance of downstream adverse events,” he said.
Dr. Pandey reported having no financial conflicts of interest regarding his study, conducted free of commercial support.
SOURCE: Pandey A. AHA 2019 Abstract EP.AOS.521.141
REPORTING FROM AHA 2019
FDA advisers set high bar for new opioids
During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?
On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.
The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.
Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.
A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.
In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.
“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.
Tramadol plus celecoxib gains some support
The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.
In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”
Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.
Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.
“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.
But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.
“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.
Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.
“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.
“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.
“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.
What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.
“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.
Two other opioids faced greater opposition
The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.
“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.
The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.
“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.
“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,
The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.
“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.
“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.
Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.
“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”
During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?
On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.
The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.
Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.
A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.
In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.
“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.
Tramadol plus celecoxib gains some support
The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.
In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”
Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.
Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.
“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.
But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.
“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.
Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.
“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.
“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.
“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.
What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.
“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.
Two other opioids faced greater opposition
The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.
“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.
The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.
“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.
“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,
The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.
“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.
“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.
Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.
“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”
During an opioid-addiction epidemic, can any new opioid pain drug meet prevailing safety demands to gain regulatory approval?
On Jan. 14 and 15, a Food and Drug Administration advisory committee voted virtually unanimously against two new opioid formulations and evenly split for and against a third; the 2 days of data and discussion showed how high a bar new opioids face these days for getting onto the U.S. market.
The bar’s height is very understandable given how many Americans have become addicted to opioids over the past decade, more often than not by accident while using pain medications as they believed they had been directed, said experts during the sessions held on the FDA’s campus in White Oak, Md.
Among the many upshots of the opioid crisis, the meetings held to discuss these three contender opioids highlighted the bitter irony confronting attempts to bring new, safer opioids to the U.S. market: While less abusable pain-relief medications that still harness the potent analgesic power of mu opioid receptor agonists are desperately desired, new agents in this space now receive withering scrutiny over their safeguards against misuse and abuse, and over whether they add anything meaningfully new to what’s already available. While these demands seem reasonable, perhaps even essential, it’s unclear whether any new opioid-based pain drugs will ever fully meet the safety that researchers, clinicians, and the public now seek.
A special FDA advisory committee that combined the Anesthetic and Analgesic Drug Products Advisory Committee with members of the Drug Safety and Risk Management Advisory Committee considered the application for three different opioid drugs from three separate companies. None received a clear endorsement. Oxycodegol, a new type of orally delivered opioid molecule engineered to slow brain entry and thereby delay an abuser’s high, got voted down without any votes in favor and 27 votes against agency approval. Aximris XR, an extended-release oxycodone formulation that successfully deterred intravenous abuse but had no deterrence efficacy for intranasal or oral abuse failed by a 2-24 vote against. The third agent, CTC, a novel formulation of the schedule IV opioid tramadol with the NSAID celecoxib designed to be analgesic but with limited opioid-abuse appeal, came the closest to meaningful support with a tied 13-13 vote from advisory committee members for and against agency approval. FDA staff takes advisory committee opinions and votes into account when making their final decisions about drug marketing approvals.
In each case, the committee members, mostly the same roster assembled for each of the three agents, identified specific concerns with the data purported to show each drug’s safety and efficacy. But the gathered experts and consumer representatives also consistently cited holistic challenges to approving new opioids and the stiffer criteria these agents face amid a continuing wave of opioid misuse and abuse.
“In the context of the public health issues, we don’t want to be perceived in any way of taking shortcuts,” said Linda S. Tyler, PharmD,, an advisory committee member and professor of pharmacy and chief pharmacy officer at the University of Utah in Salt Lake City. “There is no question that for a new product to come to market in this space it needs to add to what’s on the market, meet a high bar, and provide advantages compared with what’s already on the market,” she said.
Tramadol plus celecoxib gains some support
The proposed combined formulation of tramadol and celecoxib came closest to meeting that bar, as far as the advisory committee was concerned, coming away with 13 votes favoring approval to match 13 votes against. The premise behind this agent, know as CTC (cocrystal of tramadol and celecoxib), was that it combined a modest dose (44 mg) of the schedule IV opioid tramadol with a 56-mg dose of celecoxib in a twice-daily pill. Eugene R. Viscusi, MD, professor of anesthesiology and director of acute pain management at Thomas Jefferson University in Philadelphia and a speaker at the session on behalf of the applicant company, spelled out the rationale behind CTC: “We are caught in a dilemma. We need to reduce opioid use, but we also need to treat pain. We have an urgent need to have pain treatment options that are effective but have low potential for abuse and dependence. We are looking at multimodal analgesia, that uses combination of agents, recognizing that postoperative pain is a mixed pain syndrome. Multimodal pain treatments are now considered standard care. We want to minimize opioids to the lowest dose possible to produce safe analgesia. Tramadol is the least-preferred opioid for abuse,” and is rated as schedule IV, the U.S. designation for drugs considered to have a low level of potential for causing abuse or dependence. “Opioids used as stand-alone agents have contributed to the current opioid crisis,” Dr. Viscusi told the committee.
In contrast to tramadol’s schedule IV status, the mainstays of recent opioid pain therapy have been hydrocodone and oxycodone, schedule II opioids rated as having a “high potential for abuse.”
Several advisory committee members agreed that CTC minimized patient exposure to an opioid. “This drug isn’t even tramadol; it’s tramadol light. It has about as low a dose [of an opioid] as you can have and still have a drug,” said member Lee A. Hoffer, PhD, a medical anthropologist at Case Western Reserve University, Cleveland, who studies substance use disorders. “All opioids are dangerous, even at a low dose, but there is a linear relationship based on potency, so if we want to have an opioid for acute pain, I’d like it to have the lowest morphine milligram equivalent possible. The ideal is no opioids, but that is not what happens,” he said. The CTC formulation delivers 17.6 morphine milligram equivalents (MME) per pill, the manufacturer’s representatives said. The Centers for Disease Control and Prevention defines a “relatively low” daily opioid dose as 20-50 MME.
Some committee members hailed the CTC formulation as a meaningful step toward cutting opioid consumption.
“We may be very nervous about abuse of scheduled opioids, but a schedule IV opioid in an opioid-sparing formulation is as good as it gets in 2020,” said committee member Kevin L. Zacharoff, MD, a pain medicine specialist at the State University of New York at Stony Brook. “Any opioid has potential for abuse, but this is a safer alternative to the schedule II drugs. There is less public health risk with this,” said committee member Sherif Zaafran, MD, a Houston anesthesiologist. “This represents an incremental but important approach to addressing the opioid crisis, especially if used to replace schedule II opioids,” said Brandon D.L. Marshall, PhD, an epidemiologist and substance abuse researcher at Brown University in Providence, R.I.
But despite agreement that CTC represented a new low in the MME of an opioid given to patients, several committee members still saw the formulation as problematic by introducing any opioid, no matter how small the dose.
“The landscape of tramadol use and prescribing is evolving. There’s been an exponential upturn in tramadol prescribing. It’s perceived [as] safer, but it’s not completely safe. Will this change tramadol abuse and open the door to abuse of other opioids? This is what got us into trouble with opioids in the first place. Patients start with a prescription opioid that they perceive is safe. Patients don’t start with oxycodone or heroin. They start with drugs that are believed to be safe. I feel this combination has less risk for abuse, but I’m worried that it would produce a false sense of security for tolerability and safety,” said committee member Maryann E. Amirshahi, MD, a medical toxicologist at Georgetown University and MedStar Health in Washington.
Several other committee members returned to this point throughout the 2 days of discussions: The majority of Americans who have become hooked on opioids reached that point by taking an opioid pain medication for a legitimate medical reason and using the drug the way they had understood they should.
“I’m most concerned about unintentional misuse leading to addiction and abuse. Most people with an opioid addiction got it inadvertently, misusing it by mistake,” said committee member Suzanne B. Robotti, a consumer representative and executive director of DES Action USA. “I’m concerned about approving an opioid, even an opioid with a low abuse history, without a clearer picture of the human abuse potential data and what would happen if this drug were abused,” she added, referring to the proposed CTC formulation.
“All the patients I work with started [their opioid addiction] as pain patients,” Dr. Hoffer said.
“The most common use and abuse of opioids is orally. We need to avoid having patients who use the drug as prescribed and still end up addicted,” said committee member Friedhelm Sandbrink, MD, a neurologist and director of pain management at the Veterans Affairs (VA) Medical Center in Washington.
What this means, said several panelists, is functionally clamping down a class-wide lid on new opioids. “The way to reduce deaths from abuse is to reduce addiction, and to have an impact you need to reduce opioid exposure.” said committee member Sonia Hernandez-Diaz, MD, professor of epidemiology at the Harvard School of Public Health in Boston.
“In this opioid crisis, we ask for data that we wouldn’t ordinarily ask for. I feel there are unanswered questions about the abuse potential [of CTC]. We have seen a recent reduction in oxycodone use, which is great, but also an increase in tramadol use. We should not be fooled. Tramadol is an opioid, even if it’s schedule IV,” Dr. Tyler said.
Two other opioids faced greater opposition
The other two agents that the committee considered received much less support and sharper skepticism. The application for Aximris XR, an extended release form of oxycodone with a purported abuse-deterrent formulation (ADF) that relies on being difficult to extract for intravenous use as well as possibly having effective deterrence mechanisms for other forms of abuse. But FDA staffers reported that the only effective deterrence they could document was against manipulation for intravenous use, making Aximris XR the first opioid seeking ADF labeling based on deterrence to a single delivery route. This led several committee members, as well as the FDA, to comment on the clinical meaningfulness of ADF for one route. So far, the FDA approved ADF labeling for seven opioids, most notably OxyContin, an extended-release oxycodone with the biggest share of the U.S. market for opioids with ADF labeling.
“For ADF, we label based on what we expect from the premarket data. We don’t really know how that translates into what happens once the drug is on the market. Every company with an ADF in their label is required to do postmarketing studies on the abuse routes that are supposed to be deterred. We see shifts to other routes. Assessment of ADF is incredibly challenging, both scientifically and logistically, because there has not been a lot of uptake of these products, for a variety of reasons,” said Judy Staffa, PhD, associate director for Public Health Initiatives in the Office of Surveillance & Epidemiology in the FDA’s Center for Drug Evaluation and Research. The company that markets OxyContin has been the first to submit to the FDA all of its required postmarketing data on ADF efficacy, and the agency is now reviewing this filing, Dr. Staffa said.
The data presented for Aximris XR appeared to generally fail to convince committee members that it provided a meaningful addition to the range of opioids with ADF designations already available, which meant that their decision mostly came down to whether they felt it made sense to bring a me-too opioid to the U.S. market. Their answer was mostly no.
“In the end, it’s another opioid, and I’m not sure we need another opioid,” said committee member Lonnie K. Zeltzer, MD, professor of pediatrics, anesthesiology, psychiatry, and biobehavioral sciences and director of pediatric pain at the University of California, Los Angeles “There are so many options for patients and for people who abuse these drug. I don’t see this formulation as having a profound impact, but I’m very concerned about adding more prescription opioids,” said Martin Garcia-Bunuel, MD, deputy chief of staff for the VA Maryland Health Care System in Baltimore. Another concern of some committee members was that ADF remains a designation with an uncertain meaning, pending the FDA’s analysis of the OxyContin data.
“At the end of the day, we don’t know whether any of the [ADF] stuff makes a difference,” noted Steve B. Meisel, PharmD, system director of medication safety for M Health Fairview in Minneapolis and a committee member,
The third agent, oxycodegol, a molecule designed to pass more slowly across the blood-brain barrier because of an attached polyethylene glycol chain that’s supposed to prevent a rapid high after ingestion and hence cut abuse potential. It received unanimous committee rejection, primarily because its safety and efficacy evidence had so many holes, but the shadow of opioid abuse permeated the committee’s discussion.
“One dogma in the abuse world is that slowing entry into the brain reduces abuse potential, but the opioid crisis showed that this is not the only factor. Some people have become addicted to slow-acting drugs. The abuse potential of this drug, oxycodegol, needs to be considered given where we’ve been with the opioid crisis,” said Jane B. Acri, PhD, chief of the Medications Discovery and Toxicology Branch of the National Institute on Drug Abuse.
“During the opioid epidemic, do we want to approve more opioids? If the [pain] efficacy is about the same as oxycodone, is better safety or abuse potential a reason to approve it? We need guidance [from the FDA] about what is ‘better enough.’ No opioid will ever be perfect; there will always be abuse and misuse. But what is good enough to justify bringing another opioid onto the market? What is a good enough improvement? I don’t have an answer,” Dr. Hernandez-Diaz said.
Adviser comments showed that the continued threat of widespread opioid addiction has cooled prospects for new opioid approvals by making FDA advisers skittish over how to properly score the incremental value of a new opioid.
“Do we need to go back to the drawing board on how we make decisions on exposing the American public to these kinds of agents?” Dr. Garcia-Bunuel asked. “I don’t think we have the tools to make these decisions.”
Nontuberculous mycobacterial lung disease cases on the rise across U.S.
To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.
A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.
From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).
The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.
“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.
“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”
The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”
The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.
SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.
To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.
A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.
From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).
The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.
“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.
“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”
The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”
The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.
SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.
To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.
A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.
From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).
The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.
“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.
“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”
The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”
The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.
SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.
FROM ANNALS OF THE AMERICAN THORACIC SOCIETY
Reducing alarm fatigue in the hospital
Noise increases patient anxiety
Researchers are exploring ways to make alarms and monitors less irritating and more informative.
“Hospitals today can be sonic hellscapes, which studies have shown regularly exceed levels set by the World Health Organization: droning IV pumps, ding-donging nurse call buttons, voices crackling on loudspeakers, ringing telephones, beeping elevators, buzzing ID scanners, clattering carts, coughing, screaming, vomiting,” according to a recent article in the New York Times.
And that’s not to mention all the alarms that blare regularly, day and night. “A single patient might trigger hundreds each day, challenging caregivers to figure out which machine is beeping, and what is wrong with the patient, if anything,” according to the article.
All this noise contributes to patient anxiety and delirium and to staff burnout too. Alarm fatigue is a serious problem, related to the high rate of false alarms, the lack of alarm standardization, and the number of medical devices that emit an alarm. Its effect is to make caregivers less responsive.
A group of researchers is developing new sounds that could replace current alarms. These new signals might mimic electronic dance music or the sounds of a heartbeat; they may combine audible alarms with visual cues such as interactive screens; they will certainly be quieter. Testing remains to be done around how quickly clinicians will be able to learn the sounds and how loud they need to be. The researchers say a new standard is likely to go into effect in 2020.
Reference
1. Rueb ES. To Reduce Hospital Noise, Researchers Create Alarms That Whistle and Sing. New York Times. July 9, 2019.
Noise increases patient anxiety
Noise increases patient anxiety
Researchers are exploring ways to make alarms and monitors less irritating and more informative.
“Hospitals today can be sonic hellscapes, which studies have shown regularly exceed levels set by the World Health Organization: droning IV pumps, ding-donging nurse call buttons, voices crackling on loudspeakers, ringing telephones, beeping elevators, buzzing ID scanners, clattering carts, coughing, screaming, vomiting,” according to a recent article in the New York Times.
And that’s not to mention all the alarms that blare regularly, day and night. “A single patient might trigger hundreds each day, challenging caregivers to figure out which machine is beeping, and what is wrong with the patient, if anything,” according to the article.
All this noise contributes to patient anxiety and delirium and to staff burnout too. Alarm fatigue is a serious problem, related to the high rate of false alarms, the lack of alarm standardization, and the number of medical devices that emit an alarm. Its effect is to make caregivers less responsive.
A group of researchers is developing new sounds that could replace current alarms. These new signals might mimic electronic dance music or the sounds of a heartbeat; they may combine audible alarms with visual cues such as interactive screens; they will certainly be quieter. Testing remains to be done around how quickly clinicians will be able to learn the sounds and how loud they need to be. The researchers say a new standard is likely to go into effect in 2020.
Reference
1. Rueb ES. To Reduce Hospital Noise, Researchers Create Alarms That Whistle and Sing. New York Times. July 9, 2019.
Researchers are exploring ways to make alarms and monitors less irritating and more informative.
“Hospitals today can be sonic hellscapes, which studies have shown regularly exceed levels set by the World Health Organization: droning IV pumps, ding-donging nurse call buttons, voices crackling on loudspeakers, ringing telephones, beeping elevators, buzzing ID scanners, clattering carts, coughing, screaming, vomiting,” according to a recent article in the New York Times.
And that’s not to mention all the alarms that blare regularly, day and night. “A single patient might trigger hundreds each day, challenging caregivers to figure out which machine is beeping, and what is wrong with the patient, if anything,” according to the article.
All this noise contributes to patient anxiety and delirium and to staff burnout too. Alarm fatigue is a serious problem, related to the high rate of false alarms, the lack of alarm standardization, and the number of medical devices that emit an alarm. Its effect is to make caregivers less responsive.
A group of researchers is developing new sounds that could replace current alarms. These new signals might mimic electronic dance music or the sounds of a heartbeat; they may combine audible alarms with visual cues such as interactive screens; they will certainly be quieter. Testing remains to be done around how quickly clinicians will be able to learn the sounds and how loud they need to be. The researchers say a new standard is likely to go into effect in 2020.
Reference
1. Rueb ES. To Reduce Hospital Noise, Researchers Create Alarms That Whistle and Sing. New York Times. July 9, 2019.
Children with resistant UTIs unexpectedly may respond to discordant antibiotics
Children with urinary tract infections (UTIs) may improve clinically, and pyuria may resolve, during empiric treatment with an antibiotic that turns out to be discordant, according a retrospective study in Pediatrics.
“The low rate of care escalation and high rate of clinical improvement while on discordant antibiotics suggests that, for most patients, it would be reasonable to continue current empiric antibiotic practices until urine culture sensitivities return,” said first author Marie E. Wang, MD, a pediatric hospitalist at Stanford (Calif.) University, and colleagues.
The researchers examined the initial clinical response and escalation of care for 316 children with UTIs who received therapy to which the infecting isolate was not susceptible. The study included patients who had infections that were resistant to third-generation cephalosporins – that is, urinalysis found that the infections were not susceptible to ceftriaxone or cefotaxime in vitro. Before the resistant organisms were identified, however, the patients were started on discordant antibiotics.
Escalation of care was uncommon
The patients had a median age of 2.4 years, and 78% were girls. Approximately 90% were started on a cephalosporin, and about 65% received a first-generation cephalosporin. Patients presented during 2012-2017 to one of five children’s hospitals or to a large managed care organization with 10 hospitals in the United States. The investigators defined care escalation as a visit to the emergency department, hospitalization, or transfer to the ICU.
In all, seven patients (2%) had escalation of care on discordant antibiotics. Four children visited an emergency department without hospitalization, and three children were hospitalized because of persistent symptoms.
Among 230 cases for which the researchers had data about clinical response at a median follow-up of 3 days, 84% “had overall clinical improvement while on discordant antibiotics,” the authors said.
For 22 children who had repeat urine testing while on discordant antibiotics, 53% had resolution of pyuria, and 32% had improvement of pyuria, whereas 16% did not have improvement. Of the three patients without improvement, one had no change, and two had worsening.
Of 17 patients who had a repeat urine culture on discordant therapy, 65% had a negative repeat culture, and 18% grew the same pathogen with a decreased colony count. Two patients had a colony count that remained unchanged, and one patient had an increased colony count.
Small studies outside the United States have reported similar results, the researchers noted. Spontaneous resolution of UTIs or antibiotics reaching a sufficient concentration in the urine and renal parenchyma to achieve a clinical response are possible explanations for the findings, they wrote.
“Few children required escalation of care and most experienced initial clinical improvement,” noted Dr. Wang and colleagues. “Furthermore, in the small group of children that underwent repeat urine testing while on discordant therapy, most had resolution or improvement in pyuria and sterilization of their urine cultures. Our findings suggest that Additionally, given that these patients initially received what would generally be considered inadequate treatment, our findings may provide some insight into the natural history of UTIs and/or trigger further investigation into the relationship between in vitro urine culture susceptibilities and in vivo clinical response to treatment.”
‘Caution is needed’
The study “highlights an intriguing observation about children with UTIs unexpectedly responding to discordant antibiotic therapy,” Tej K. Mattoo, MD, and Basim I. Asmar, MD, wrote in an accompanying commentary.(doi: 10.1542/peds.2019-3512). Dr. Mattoo and Dr. Asmar, a pediatric nephrologist and a specialist in pediatric infectious diseases, respectively, at Wayne State University and affiliated with Children’s Hospital of Michigan, both in Detroit.
In an inpatient setting, it may be easy for physicians to reassess patients “once urine culture results reveal resistance to the treating antibiotic,” they noted. In an ambulatory setting, however, “it is likely that some patients will receive a full course of an antibiotic that does not have in vitro activity against the urinary pathogen.”
Physicians have a responsibility to use antibiotics judiciously, they said. Widely accepted principles include avoiding repeated courses of antibiotics, diagnosing UTIs appropriately, and not treating asymptomatic bacteriuria.
The study had no external funding. The authors had no relevant financial disclosures.
SOURCE: Wang ME et al. Pediatrics. 2020 Jan 17. doi: 10.1542/peds.2019-1608.
This article was updated 2/4/2020.
Children with urinary tract infections (UTIs) may improve clinically, and pyuria may resolve, during empiric treatment with an antibiotic that turns out to be discordant, according a retrospective study in Pediatrics.
“The low rate of care escalation and high rate of clinical improvement while on discordant antibiotics suggests that, for most patients, it would be reasonable to continue current empiric antibiotic practices until urine culture sensitivities return,” said first author Marie E. Wang, MD, a pediatric hospitalist at Stanford (Calif.) University, and colleagues.
The researchers examined the initial clinical response and escalation of care for 316 children with UTIs who received therapy to which the infecting isolate was not susceptible. The study included patients who had infections that were resistant to third-generation cephalosporins – that is, urinalysis found that the infections were not susceptible to ceftriaxone or cefotaxime in vitro. Before the resistant organisms were identified, however, the patients were started on discordant antibiotics.
Escalation of care was uncommon
The patients had a median age of 2.4 years, and 78% were girls. Approximately 90% were started on a cephalosporin, and about 65% received a first-generation cephalosporin. Patients presented during 2012-2017 to one of five children’s hospitals or to a large managed care organization with 10 hospitals in the United States. The investigators defined care escalation as a visit to the emergency department, hospitalization, or transfer to the ICU.
In all, seven patients (2%) had escalation of care on discordant antibiotics. Four children visited an emergency department without hospitalization, and three children were hospitalized because of persistent symptoms.
Among 230 cases for which the researchers had data about clinical response at a median follow-up of 3 days, 84% “had overall clinical improvement while on discordant antibiotics,” the authors said.
For 22 children who had repeat urine testing while on discordant antibiotics, 53% had resolution of pyuria, and 32% had improvement of pyuria, whereas 16% did not have improvement. Of the three patients without improvement, one had no change, and two had worsening.
Of 17 patients who had a repeat urine culture on discordant therapy, 65% had a negative repeat culture, and 18% grew the same pathogen with a decreased colony count. Two patients had a colony count that remained unchanged, and one patient had an increased colony count.
Small studies outside the United States have reported similar results, the researchers noted. Spontaneous resolution of UTIs or antibiotics reaching a sufficient concentration in the urine and renal parenchyma to achieve a clinical response are possible explanations for the findings, they wrote.
“Few children required escalation of care and most experienced initial clinical improvement,” noted Dr. Wang and colleagues. “Furthermore, in the small group of children that underwent repeat urine testing while on discordant therapy, most had resolution or improvement in pyuria and sterilization of their urine cultures. Our findings suggest that Additionally, given that these patients initially received what would generally be considered inadequate treatment, our findings may provide some insight into the natural history of UTIs and/or trigger further investigation into the relationship between in vitro urine culture susceptibilities and in vivo clinical response to treatment.”
‘Caution is needed’
The study “highlights an intriguing observation about children with UTIs unexpectedly responding to discordant antibiotic therapy,” Tej K. Mattoo, MD, and Basim I. Asmar, MD, wrote in an accompanying commentary.(doi: 10.1542/peds.2019-3512). Dr. Mattoo and Dr. Asmar, a pediatric nephrologist and a specialist in pediatric infectious diseases, respectively, at Wayne State University and affiliated with Children’s Hospital of Michigan, both in Detroit.
In an inpatient setting, it may be easy for physicians to reassess patients “once urine culture results reveal resistance to the treating antibiotic,” they noted. In an ambulatory setting, however, “it is likely that some patients will receive a full course of an antibiotic that does not have in vitro activity against the urinary pathogen.”
Physicians have a responsibility to use antibiotics judiciously, they said. Widely accepted principles include avoiding repeated courses of antibiotics, diagnosing UTIs appropriately, and not treating asymptomatic bacteriuria.
The study had no external funding. The authors had no relevant financial disclosures.
SOURCE: Wang ME et al. Pediatrics. 2020 Jan 17. doi: 10.1542/peds.2019-1608.
This article was updated 2/4/2020.
Children with urinary tract infections (UTIs) may improve clinically, and pyuria may resolve, during empiric treatment with an antibiotic that turns out to be discordant, according a retrospective study in Pediatrics.
“The low rate of care escalation and high rate of clinical improvement while on discordant antibiotics suggests that, for most patients, it would be reasonable to continue current empiric antibiotic practices until urine culture sensitivities return,” said first author Marie E. Wang, MD, a pediatric hospitalist at Stanford (Calif.) University, and colleagues.
The researchers examined the initial clinical response and escalation of care for 316 children with UTIs who received therapy to which the infecting isolate was not susceptible. The study included patients who had infections that were resistant to third-generation cephalosporins – that is, urinalysis found that the infections were not susceptible to ceftriaxone or cefotaxime in vitro. Before the resistant organisms were identified, however, the patients were started on discordant antibiotics.
Escalation of care was uncommon
The patients had a median age of 2.4 years, and 78% were girls. Approximately 90% were started on a cephalosporin, and about 65% received a first-generation cephalosporin. Patients presented during 2012-2017 to one of five children’s hospitals or to a large managed care organization with 10 hospitals in the United States. The investigators defined care escalation as a visit to the emergency department, hospitalization, or transfer to the ICU.
In all, seven patients (2%) had escalation of care on discordant antibiotics. Four children visited an emergency department without hospitalization, and three children were hospitalized because of persistent symptoms.
Among 230 cases for which the researchers had data about clinical response at a median follow-up of 3 days, 84% “had overall clinical improvement while on discordant antibiotics,” the authors said.
For 22 children who had repeat urine testing while on discordant antibiotics, 53% had resolution of pyuria, and 32% had improvement of pyuria, whereas 16% did not have improvement. Of the three patients without improvement, one had no change, and two had worsening.
Of 17 patients who had a repeat urine culture on discordant therapy, 65% had a negative repeat culture, and 18% grew the same pathogen with a decreased colony count. Two patients had a colony count that remained unchanged, and one patient had an increased colony count.
Small studies outside the United States have reported similar results, the researchers noted. Spontaneous resolution of UTIs or antibiotics reaching a sufficient concentration in the urine and renal parenchyma to achieve a clinical response are possible explanations for the findings, they wrote.
“Few children required escalation of care and most experienced initial clinical improvement,” noted Dr. Wang and colleagues. “Furthermore, in the small group of children that underwent repeat urine testing while on discordant therapy, most had resolution or improvement in pyuria and sterilization of their urine cultures. Our findings suggest that Additionally, given that these patients initially received what would generally be considered inadequate treatment, our findings may provide some insight into the natural history of UTIs and/or trigger further investigation into the relationship between in vitro urine culture susceptibilities and in vivo clinical response to treatment.”
‘Caution is needed’
The study “highlights an intriguing observation about children with UTIs unexpectedly responding to discordant antibiotic therapy,” Tej K. Mattoo, MD, and Basim I. Asmar, MD, wrote in an accompanying commentary.(doi: 10.1542/peds.2019-3512). Dr. Mattoo and Dr. Asmar, a pediatric nephrologist and a specialist in pediatric infectious diseases, respectively, at Wayne State University and affiliated with Children’s Hospital of Michigan, both in Detroit.
In an inpatient setting, it may be easy for physicians to reassess patients “once urine culture results reveal resistance to the treating antibiotic,” they noted. In an ambulatory setting, however, “it is likely that some patients will receive a full course of an antibiotic that does not have in vitro activity against the urinary pathogen.”
Physicians have a responsibility to use antibiotics judiciously, they said. Widely accepted principles include avoiding repeated courses of antibiotics, diagnosing UTIs appropriately, and not treating asymptomatic bacteriuria.
The study had no external funding. The authors had no relevant financial disclosures.
SOURCE: Wang ME et al. Pediatrics. 2020 Jan 17. doi: 10.1542/peds.2019-1608.
This article was updated 2/4/2020.
FROM PEDIATRICS
SHM Pediatric Core Competencies get fresh update
New core competencies reflect a decade of change
Over the past 10 years, much has changed in the world of pediatric hospital medicine. The annual national PHM conference sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics (AAP), and the Academic Pediatric Association (APA) is robust; textbooks and journal articles in the field abound; and networks and training in research, quality improvement, and education are successful and ongoing.
Much of this did not exist or was in its infancy back in 2010. Since then, it has grown and greatly evolved. In parallel, medicine and society have changed. These influences on health care, along with the growth of the field over time, prompted a review and revision of the 2010 PHM Core Competencies published by SHM. With support from the society, the Pediatric Hospital Medicine Special Interest Group launched the plan for revision of the PHM Core Competencies.
The selected editors included Sandra Gage, MD, PhD, SFHM, of Phoenix Children’s Hospital; Erin Stucky Fisher, MD, MHM, of UCSD/Rady Children’s Hospital in San Diego; Jennifer Maniscalco, MD, MPH, of Johns Hopkins All Children’s Hospital in St. Petersburg, Fla.; and Sofia Teferi, MD, SFHM, a pediatric hospitalist based at Bon Secours St. Mary’s Hospital in Richmond, Va. They began their work in 2017 along with six associate editors, meeting every 2 weeks via conference call, dividing the work accordingly.
Dr. Teferi served in a new and critical role as contributing editor. She described her role as a “sweeper” of sorts, bringing her unique perspective to the process. “The other three members are from academic settings, and I’m from a community setting, which is very different,” Dr. Teferi said. “I went through all the chapters to ensure they were inclusive of the community setting.”
According to Dr. Gage, “the purpose of the original PHM Core Competencies was to define the roles and responsibilities of a PHM practitioner. In the intervening 10 years, the field has changed and matured, and we have solidified our role since then.”
Today’s pediatric hospitalists, for instance, may coordinate care in EDs, provide inpatient consultations, engage or lead quality improvement programs, and teach. The demands for pediatric hospital care today go beyond the training provided in a standard pediatric residency. The core competencies need to provide the information necessary, therefore, to ensure pediatric hospital medicine is practiced at its most informed level.
A profession transformed
At the time of the first set of core competencies, there were over 2,500 members in three core societies in which pediatric hospitalists were members: the AAP, the APA, and SHM. As of 2017, those numbers have swelled as the care for children in the hospital setting has shifted away from these patients’ primary care providers.
The original core competencies included 54 chapters, designed to be used independent of the others. They provided a foundation for the creation of pediatric hospital medicine and served to standardize and improve inpatient training practices.
For the new core competencies, every single chapter was reviewed line by line, Dr. Gage said. Many chapters had content modified, and new chapters were added to reflect the evolution of the field and of medicine. “We added about 14 new chapters, adjusted the titles of others, and significantly changed the content of over half,” Dr. Gage explained. “They are fairly broad changes, related to the breadth of the practice today.”
Dr. Teferi noted that practitioners can use the updated competencies with additions to the service lines that have arisen since the last version. “These include areas like step down and newborn nursery, things that weren’t part of our portfolio 10 years ago,” she said. “This reflects the fact that often you’ll see a hospital leader who might want to add to a hospitalist’s portfolio of services because there is no one else to do it. Or maybe community pediatrics no longer want to treat babies, so we add that. The settings vary widely today and we need the competencies to address that.”
Practices within these settings can also vary widely. Teaching, palliative care, airway management, critical care, and anesthesia may all come into play, among other factors. Research opportunities throughout the field also continue to expand.
Dr. Fisher said that the editors and associate editors kept in mind the fact that not every hospital would have all the resources necessary at its fingertips. “The competencies must reflect the realities of the variety of community settings,” she said. “Also, on a national level, the majority of pediatric patients are not seen in a children’s hospital. Community sites are where pediatric hospitalists are not only advocates for care, but can be working with limited resources – the ‘lone soldiers.’ We wanted to make sure the competencies reflect that reality and environment community site or not; academic site or not; tertiary care site or not; rural or not – these are overlapping but independent considerations for all who practice pediatric hospital medicine – a Venn diagram, and the PHM core competencies try to attend to all of those.”
This made Dr. Teferi’s perspective all the more important. “While many, including other editors and associate editors, work in community sites, Dr. Teferi has this as her unique and sole focus. She brought a unique viewpoint to the table,” Dr. Fisher said.
A goal of the core competencies is to make it possible for a pediatric hospitalist to move to a different practice environment and still provide the same level of high-quality care. “It’s difficult but important to grasp the concepts and competencies of various settings,” Dr. Fisher said. “In this way, our competencies are a parallel model to the adult hospitalist competencies.”
The editors surveyed practitioners across the country to gather their input on content, and brought on topic experts to write the new chapters. “If we didn’t have an author for a specific chapter or area from the last set of competencies, we came to a consensus on who the new one should be,” Dr. Gage explained. “We looked for known and accepted experts in the field by reviewing the literature and conference lecturers at all major PHM meetings.”
Once the editors and associate editors worked with authors to refine their chapter(s), the chapters were sent to multiple external reviewers including subgroups of SHM, AAP, and APA, as well as a variety of other associations. They provided input that the editors and associate editors collated, reviewed, and incorporated according to consensus and discussion with the authors.
A preview
As far as the actual changes go, some of new chapters include four common clinical, two core skills, three specialized services, and five health care systems, with many others undergoing content changes, according to Dr. Gage.
Major considerations in developing the new competencies include the national trend of rising mental health issues among young patients. According to the AAP, over the last decade the number of young people aged 6-17 years requiring mental health care has risen from 9% to more than 14%. In outpatient settings, many pediatricians report that half or more of their visits are dedicated to these issues, a number that may spill out into the hospital setting as well.
According to Dr. Fisher, pediatric hospitalists today see increasing numbers of chronic and acute diseases accompanied by mental and behavioral health issues. “We wanted to underscore this complexity in the competencies,” she explained. “We needed to focus new attention on how to identify and treat children with behavioral or psychiatric diagnoses or needs.”
Other new areas of focus include infection care and antimicrobial stewardship. “We see kids on antibiotics in hospital settings and we need to focus on narrowing choices, decreasing use, and shortening duration,” Dr. Gage said.
Dr. Maniscalco said that, overall, the changes represent the evolution of the field. “Pediatric hospitalists are taking on far more patients with acute and complex issues,” she explained. “Our skill set is coming into focus.”
Dr. Gage added that there is an increased need for pediatric hospitalists to be adept at “managing acute psychiatric care and navigating the mental health care arena.”
There’s also the growing need for an understanding of neonatal abstinence and opioid withdrawal syndrome. “This is definitely a hot topic and one that most hospitalists must address today,” Dr. Gage said. “That wasn’t the case a decade ago.”
Hospital care for pediatrics today often means a team effort, including pediatric hospitalists, surgeons, mental health professionals, and others. Often missing from the picture today are primary care physicians, who instead refer a growing percentage of their patients to hospitalists. The pediatric hospitalist’s role has evolved and grown from what it was 10 years ago, as reflected in the competencies.
“We are very much coordinating care and collaborating today in ways we weren’t 10 years ago,” said Dr. Gage. “There’s a lot more attention on creating partnerships. While we may not always be the ones performing procedures, we will most likely take part in patient care, especially as surgeons step farther away from care outside of the OR.”
The field has also become more family centered, said Dr. Gage. “All of health care today is more astute about the participation of families in care,” she said. “We kept that in mind in developing the competencies.”
Also important in this set of competencies was the concept of high-value care using evidence-based medicine.
Into the field
How exactly the core competencies will be utilized from one hospital or setting to the next will vary, said Dr. Fisher. “For some sites, they can aid existing teaching programs, and they will most likely adapt their curriculum to address the new competencies, informing how they teach.”
Even in centers where there isn’t a formal academic role, teaching still occurs. “Pediatric hospitalists have roles on committees and projects, and giving a talk to respiratory therapists, having group meetings – these all involve teaching in some form,” Dr. Fisher said. “Most physicians will determine how they wish to insert the competencies into their own education, as well as use them to educate others.”
Regardless of how they may be used locally, Dr. Fisher anticipates that the entire pediatric hospitalist community will appreciate the updates. “The competencies address our rapidly changing health care environment,” she said. “We believe the field will benefit from the additions and changes.”
Indeed, the core competencies will help standardize and improve consistency of care across the board. Improved efficiencies, economics, and practices are all desired and expected outcomes from the release of the revised competencies.
To ensure that the changes to the competencies are highlighted in settings nationwide, the editors and associate editors hope to present about them at upcoming conferences, including at the SHM 2020 Annual Conference, the Pediatric Hospital Medicine conference, the Pediatric Academic Societies conference, and the American Pediatric Association.
“We want to present to as many venues as possible to bring people up to speed and ensure they are aware of the changes,” Dr. Teferi said. “We’ll be including workshops with visual aids, along with our presentations.”
While this update represents a 10-year evolution, the editors and the SHM Pediatric Special Interest Group do not have an exact time frame for when the core competencies will need another revision. As quickly as the profession is developing, it may be as few as 5 years, but may also be another full decade.
“Like most fields, we will continue to evolve as our roles become better defined and we gain more knowledge,” Dr. Maniscalco said. “The core competencies represent the field whether a senior pediatric hospitalist, a fellow, or an educator. They bring the field together and provide education for everyone. That’s their role.”
New core competencies reflect a decade of change
New core competencies reflect a decade of change
Over the past 10 years, much has changed in the world of pediatric hospital medicine. The annual national PHM conference sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics (AAP), and the Academic Pediatric Association (APA) is robust; textbooks and journal articles in the field abound; and networks and training in research, quality improvement, and education are successful and ongoing.
Much of this did not exist or was in its infancy back in 2010. Since then, it has grown and greatly evolved. In parallel, medicine and society have changed. These influences on health care, along with the growth of the field over time, prompted a review and revision of the 2010 PHM Core Competencies published by SHM. With support from the society, the Pediatric Hospital Medicine Special Interest Group launched the plan for revision of the PHM Core Competencies.
The selected editors included Sandra Gage, MD, PhD, SFHM, of Phoenix Children’s Hospital; Erin Stucky Fisher, MD, MHM, of UCSD/Rady Children’s Hospital in San Diego; Jennifer Maniscalco, MD, MPH, of Johns Hopkins All Children’s Hospital in St. Petersburg, Fla.; and Sofia Teferi, MD, SFHM, a pediatric hospitalist based at Bon Secours St. Mary’s Hospital in Richmond, Va. They began their work in 2017 along with six associate editors, meeting every 2 weeks via conference call, dividing the work accordingly.
Dr. Teferi served in a new and critical role as contributing editor. She described her role as a “sweeper” of sorts, bringing her unique perspective to the process. “The other three members are from academic settings, and I’m from a community setting, which is very different,” Dr. Teferi said. “I went through all the chapters to ensure they were inclusive of the community setting.”
According to Dr. Gage, “the purpose of the original PHM Core Competencies was to define the roles and responsibilities of a PHM practitioner. In the intervening 10 years, the field has changed and matured, and we have solidified our role since then.”
Today’s pediatric hospitalists, for instance, may coordinate care in EDs, provide inpatient consultations, engage or lead quality improvement programs, and teach. The demands for pediatric hospital care today go beyond the training provided in a standard pediatric residency. The core competencies need to provide the information necessary, therefore, to ensure pediatric hospital medicine is practiced at its most informed level.
A profession transformed
At the time of the first set of core competencies, there were over 2,500 members in three core societies in which pediatric hospitalists were members: the AAP, the APA, and SHM. As of 2017, those numbers have swelled as the care for children in the hospital setting has shifted away from these patients’ primary care providers.
The original core competencies included 54 chapters, designed to be used independent of the others. They provided a foundation for the creation of pediatric hospital medicine and served to standardize and improve inpatient training practices.
For the new core competencies, every single chapter was reviewed line by line, Dr. Gage said. Many chapters had content modified, and new chapters were added to reflect the evolution of the field and of medicine. “We added about 14 new chapters, adjusted the titles of others, and significantly changed the content of over half,” Dr. Gage explained. “They are fairly broad changes, related to the breadth of the practice today.”
Dr. Teferi noted that practitioners can use the updated competencies with additions to the service lines that have arisen since the last version. “These include areas like step down and newborn nursery, things that weren’t part of our portfolio 10 years ago,” she said. “This reflects the fact that often you’ll see a hospital leader who might want to add to a hospitalist’s portfolio of services because there is no one else to do it. Or maybe community pediatrics no longer want to treat babies, so we add that. The settings vary widely today and we need the competencies to address that.”
Practices within these settings can also vary widely. Teaching, palliative care, airway management, critical care, and anesthesia may all come into play, among other factors. Research opportunities throughout the field also continue to expand.
Dr. Fisher said that the editors and associate editors kept in mind the fact that not every hospital would have all the resources necessary at its fingertips. “The competencies must reflect the realities of the variety of community settings,” she said. “Also, on a national level, the majority of pediatric patients are not seen in a children’s hospital. Community sites are where pediatric hospitalists are not only advocates for care, but can be working with limited resources – the ‘lone soldiers.’ We wanted to make sure the competencies reflect that reality and environment community site or not; academic site or not; tertiary care site or not; rural or not – these are overlapping but independent considerations for all who practice pediatric hospital medicine – a Venn diagram, and the PHM core competencies try to attend to all of those.”
This made Dr. Teferi’s perspective all the more important. “While many, including other editors and associate editors, work in community sites, Dr. Teferi has this as her unique and sole focus. She brought a unique viewpoint to the table,” Dr. Fisher said.
A goal of the core competencies is to make it possible for a pediatric hospitalist to move to a different practice environment and still provide the same level of high-quality care. “It’s difficult but important to grasp the concepts and competencies of various settings,” Dr. Fisher said. “In this way, our competencies are a parallel model to the adult hospitalist competencies.”
The editors surveyed practitioners across the country to gather their input on content, and brought on topic experts to write the new chapters. “If we didn’t have an author for a specific chapter or area from the last set of competencies, we came to a consensus on who the new one should be,” Dr. Gage explained. “We looked for known and accepted experts in the field by reviewing the literature and conference lecturers at all major PHM meetings.”
Once the editors and associate editors worked with authors to refine their chapter(s), the chapters were sent to multiple external reviewers including subgroups of SHM, AAP, and APA, as well as a variety of other associations. They provided input that the editors and associate editors collated, reviewed, and incorporated according to consensus and discussion with the authors.
A preview
As far as the actual changes go, some of new chapters include four common clinical, two core skills, three specialized services, and five health care systems, with many others undergoing content changes, according to Dr. Gage.
Major considerations in developing the new competencies include the national trend of rising mental health issues among young patients. According to the AAP, over the last decade the number of young people aged 6-17 years requiring mental health care has risen from 9% to more than 14%. In outpatient settings, many pediatricians report that half or more of their visits are dedicated to these issues, a number that may spill out into the hospital setting as well.
According to Dr. Fisher, pediatric hospitalists today see increasing numbers of chronic and acute diseases accompanied by mental and behavioral health issues. “We wanted to underscore this complexity in the competencies,” she explained. “We needed to focus new attention on how to identify and treat children with behavioral or psychiatric diagnoses or needs.”
Other new areas of focus include infection care and antimicrobial stewardship. “We see kids on antibiotics in hospital settings and we need to focus on narrowing choices, decreasing use, and shortening duration,” Dr. Gage said.
Dr. Maniscalco said that, overall, the changes represent the evolution of the field. “Pediatric hospitalists are taking on far more patients with acute and complex issues,” she explained. “Our skill set is coming into focus.”
Dr. Gage added that there is an increased need for pediatric hospitalists to be adept at “managing acute psychiatric care and navigating the mental health care arena.”
There’s also the growing need for an understanding of neonatal abstinence and opioid withdrawal syndrome. “This is definitely a hot topic and one that most hospitalists must address today,” Dr. Gage said. “That wasn’t the case a decade ago.”
Hospital care for pediatrics today often means a team effort, including pediatric hospitalists, surgeons, mental health professionals, and others. Often missing from the picture today are primary care physicians, who instead refer a growing percentage of their patients to hospitalists. The pediatric hospitalist’s role has evolved and grown from what it was 10 years ago, as reflected in the competencies.
“We are very much coordinating care and collaborating today in ways we weren’t 10 years ago,” said Dr. Gage. “There’s a lot more attention on creating partnerships. While we may not always be the ones performing procedures, we will most likely take part in patient care, especially as surgeons step farther away from care outside of the OR.”
The field has also become more family centered, said Dr. Gage. “All of health care today is more astute about the participation of families in care,” she said. “We kept that in mind in developing the competencies.”
Also important in this set of competencies was the concept of high-value care using evidence-based medicine.
Into the field
How exactly the core competencies will be utilized from one hospital or setting to the next will vary, said Dr. Fisher. “For some sites, they can aid existing teaching programs, and they will most likely adapt their curriculum to address the new competencies, informing how they teach.”
Even in centers where there isn’t a formal academic role, teaching still occurs. “Pediatric hospitalists have roles on committees and projects, and giving a talk to respiratory therapists, having group meetings – these all involve teaching in some form,” Dr. Fisher said. “Most physicians will determine how they wish to insert the competencies into their own education, as well as use them to educate others.”
Regardless of how they may be used locally, Dr. Fisher anticipates that the entire pediatric hospitalist community will appreciate the updates. “The competencies address our rapidly changing health care environment,” she said. “We believe the field will benefit from the additions and changes.”
Indeed, the core competencies will help standardize and improve consistency of care across the board. Improved efficiencies, economics, and practices are all desired and expected outcomes from the release of the revised competencies.
To ensure that the changes to the competencies are highlighted in settings nationwide, the editors and associate editors hope to present about them at upcoming conferences, including at the SHM 2020 Annual Conference, the Pediatric Hospital Medicine conference, the Pediatric Academic Societies conference, and the American Pediatric Association.
“We want to present to as many venues as possible to bring people up to speed and ensure they are aware of the changes,” Dr. Teferi said. “We’ll be including workshops with visual aids, along with our presentations.”
While this update represents a 10-year evolution, the editors and the SHM Pediatric Special Interest Group do not have an exact time frame for when the core competencies will need another revision. As quickly as the profession is developing, it may be as few as 5 years, but may also be another full decade.
“Like most fields, we will continue to evolve as our roles become better defined and we gain more knowledge,” Dr. Maniscalco said. “The core competencies represent the field whether a senior pediatric hospitalist, a fellow, or an educator. They bring the field together and provide education for everyone. That’s their role.”
Over the past 10 years, much has changed in the world of pediatric hospital medicine. The annual national PHM conference sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics (AAP), and the Academic Pediatric Association (APA) is robust; textbooks and journal articles in the field abound; and networks and training in research, quality improvement, and education are successful and ongoing.
Much of this did not exist or was in its infancy back in 2010. Since then, it has grown and greatly evolved. In parallel, medicine and society have changed. These influences on health care, along with the growth of the field over time, prompted a review and revision of the 2010 PHM Core Competencies published by SHM. With support from the society, the Pediatric Hospital Medicine Special Interest Group launched the plan for revision of the PHM Core Competencies.
The selected editors included Sandra Gage, MD, PhD, SFHM, of Phoenix Children’s Hospital; Erin Stucky Fisher, MD, MHM, of UCSD/Rady Children’s Hospital in San Diego; Jennifer Maniscalco, MD, MPH, of Johns Hopkins All Children’s Hospital in St. Petersburg, Fla.; and Sofia Teferi, MD, SFHM, a pediatric hospitalist based at Bon Secours St. Mary’s Hospital in Richmond, Va. They began their work in 2017 along with six associate editors, meeting every 2 weeks via conference call, dividing the work accordingly.
Dr. Teferi served in a new and critical role as contributing editor. She described her role as a “sweeper” of sorts, bringing her unique perspective to the process. “The other three members are from academic settings, and I’m from a community setting, which is very different,” Dr. Teferi said. “I went through all the chapters to ensure they were inclusive of the community setting.”
According to Dr. Gage, “the purpose of the original PHM Core Competencies was to define the roles and responsibilities of a PHM practitioner. In the intervening 10 years, the field has changed and matured, and we have solidified our role since then.”
Today’s pediatric hospitalists, for instance, may coordinate care in EDs, provide inpatient consultations, engage or lead quality improvement programs, and teach. The demands for pediatric hospital care today go beyond the training provided in a standard pediatric residency. The core competencies need to provide the information necessary, therefore, to ensure pediatric hospital medicine is practiced at its most informed level.
A profession transformed
At the time of the first set of core competencies, there were over 2,500 members in three core societies in which pediatric hospitalists were members: the AAP, the APA, and SHM. As of 2017, those numbers have swelled as the care for children in the hospital setting has shifted away from these patients’ primary care providers.
The original core competencies included 54 chapters, designed to be used independent of the others. They provided a foundation for the creation of pediatric hospital medicine and served to standardize and improve inpatient training practices.
For the new core competencies, every single chapter was reviewed line by line, Dr. Gage said. Many chapters had content modified, and new chapters were added to reflect the evolution of the field and of medicine. “We added about 14 new chapters, adjusted the titles of others, and significantly changed the content of over half,” Dr. Gage explained. “They are fairly broad changes, related to the breadth of the practice today.”
Dr. Teferi noted that practitioners can use the updated competencies with additions to the service lines that have arisen since the last version. “These include areas like step down and newborn nursery, things that weren’t part of our portfolio 10 years ago,” she said. “This reflects the fact that often you’ll see a hospital leader who might want to add to a hospitalist’s portfolio of services because there is no one else to do it. Or maybe community pediatrics no longer want to treat babies, so we add that. The settings vary widely today and we need the competencies to address that.”
Practices within these settings can also vary widely. Teaching, palliative care, airway management, critical care, and anesthesia may all come into play, among other factors. Research opportunities throughout the field also continue to expand.
Dr. Fisher said that the editors and associate editors kept in mind the fact that not every hospital would have all the resources necessary at its fingertips. “The competencies must reflect the realities of the variety of community settings,” she said. “Also, on a national level, the majority of pediatric patients are not seen in a children’s hospital. Community sites are where pediatric hospitalists are not only advocates for care, but can be working with limited resources – the ‘lone soldiers.’ We wanted to make sure the competencies reflect that reality and environment community site or not; academic site or not; tertiary care site or not; rural or not – these are overlapping but independent considerations for all who practice pediatric hospital medicine – a Venn diagram, and the PHM core competencies try to attend to all of those.”
This made Dr. Teferi’s perspective all the more important. “While many, including other editors and associate editors, work in community sites, Dr. Teferi has this as her unique and sole focus. She brought a unique viewpoint to the table,” Dr. Fisher said.
A goal of the core competencies is to make it possible for a pediatric hospitalist to move to a different practice environment and still provide the same level of high-quality care. “It’s difficult but important to grasp the concepts and competencies of various settings,” Dr. Fisher said. “In this way, our competencies are a parallel model to the adult hospitalist competencies.”
The editors surveyed practitioners across the country to gather their input on content, and brought on topic experts to write the new chapters. “If we didn’t have an author for a specific chapter or area from the last set of competencies, we came to a consensus on who the new one should be,” Dr. Gage explained. “We looked for known and accepted experts in the field by reviewing the literature and conference lecturers at all major PHM meetings.”
Once the editors and associate editors worked with authors to refine their chapter(s), the chapters were sent to multiple external reviewers including subgroups of SHM, AAP, and APA, as well as a variety of other associations. They provided input that the editors and associate editors collated, reviewed, and incorporated according to consensus and discussion with the authors.
A preview
As far as the actual changes go, some of new chapters include four common clinical, two core skills, three specialized services, and five health care systems, with many others undergoing content changes, according to Dr. Gage.
Major considerations in developing the new competencies include the national trend of rising mental health issues among young patients. According to the AAP, over the last decade the number of young people aged 6-17 years requiring mental health care has risen from 9% to more than 14%. In outpatient settings, many pediatricians report that half or more of their visits are dedicated to these issues, a number that may spill out into the hospital setting as well.
According to Dr. Fisher, pediatric hospitalists today see increasing numbers of chronic and acute diseases accompanied by mental and behavioral health issues. “We wanted to underscore this complexity in the competencies,” she explained. “We needed to focus new attention on how to identify and treat children with behavioral or psychiatric diagnoses or needs.”
Other new areas of focus include infection care and antimicrobial stewardship. “We see kids on antibiotics in hospital settings and we need to focus on narrowing choices, decreasing use, and shortening duration,” Dr. Gage said.
Dr. Maniscalco said that, overall, the changes represent the evolution of the field. “Pediatric hospitalists are taking on far more patients with acute and complex issues,” she explained. “Our skill set is coming into focus.”
Dr. Gage added that there is an increased need for pediatric hospitalists to be adept at “managing acute psychiatric care and navigating the mental health care arena.”
There’s also the growing need for an understanding of neonatal abstinence and opioid withdrawal syndrome. “This is definitely a hot topic and one that most hospitalists must address today,” Dr. Gage said. “That wasn’t the case a decade ago.”
Hospital care for pediatrics today often means a team effort, including pediatric hospitalists, surgeons, mental health professionals, and others. Often missing from the picture today are primary care physicians, who instead refer a growing percentage of their patients to hospitalists. The pediatric hospitalist’s role has evolved and grown from what it was 10 years ago, as reflected in the competencies.
“We are very much coordinating care and collaborating today in ways we weren’t 10 years ago,” said Dr. Gage. “There’s a lot more attention on creating partnerships. While we may not always be the ones performing procedures, we will most likely take part in patient care, especially as surgeons step farther away from care outside of the OR.”
The field has also become more family centered, said Dr. Gage. “All of health care today is more astute about the participation of families in care,” she said. “We kept that in mind in developing the competencies.”
Also important in this set of competencies was the concept of high-value care using evidence-based medicine.
Into the field
How exactly the core competencies will be utilized from one hospital or setting to the next will vary, said Dr. Fisher. “For some sites, they can aid existing teaching programs, and they will most likely adapt their curriculum to address the new competencies, informing how they teach.”
Even in centers where there isn’t a formal academic role, teaching still occurs. “Pediatric hospitalists have roles on committees and projects, and giving a talk to respiratory therapists, having group meetings – these all involve teaching in some form,” Dr. Fisher said. “Most physicians will determine how they wish to insert the competencies into their own education, as well as use them to educate others.”
Regardless of how they may be used locally, Dr. Fisher anticipates that the entire pediatric hospitalist community will appreciate the updates. “The competencies address our rapidly changing health care environment,” she said. “We believe the field will benefit from the additions and changes.”
Indeed, the core competencies will help standardize and improve consistency of care across the board. Improved efficiencies, economics, and practices are all desired and expected outcomes from the release of the revised competencies.
To ensure that the changes to the competencies are highlighted in settings nationwide, the editors and associate editors hope to present about them at upcoming conferences, including at the SHM 2020 Annual Conference, the Pediatric Hospital Medicine conference, the Pediatric Academic Societies conference, and the American Pediatric Association.
“We want to present to as many venues as possible to bring people up to speed and ensure they are aware of the changes,” Dr. Teferi said. “We’ll be including workshops with visual aids, along with our presentations.”
While this update represents a 10-year evolution, the editors and the SHM Pediatric Special Interest Group do not have an exact time frame for when the core competencies will need another revision. As quickly as the profession is developing, it may be as few as 5 years, but may also be another full decade.
“Like most fields, we will continue to evolve as our roles become better defined and we gain more knowledge,” Dr. Maniscalco said. “The core competencies represent the field whether a senior pediatric hospitalist, a fellow, or an educator. They bring the field together and provide education for everyone. That’s their role.”
SPRINT-type BP control provides up to 3 years of additional life
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
PHILADELPHIA – in age-dependent fashion, compared with the older target standard BP, according to a novel analysis of data from the landmark SPRINT trial.
SPRINT randomized 9,361 hypertensive patients aged 50 years or older with at least one additional cardiovascular risk factor to intensive control with a target systolic BP of less than 120 mm Hg or to the then-standard target of less than 140 mm Hg. The trial was stopped early for ethical reasons when an interim analysis showed intensive control was associated with a 27% reduction in mortality. But that 27% reduction in mortality risk is a tough concept for many patients to interpret in practical terms, Muthiah Vaduganathan, MD, observed at the American Heart Association scientific sessions.
So he and his coinvestigators sliced and diced the mountainous SPRINT data in a novel way, using an actuarial statistical analysis.
“These actuarial data from SPRINT support the survival benefits of intensive blood pressure control, especially when initiated in middle-aged, high-risk adults. Our analysis really reaffirms the original SPRINT trial results [N Engl J Med. 2015 Nov 26;373(22):2103-16] and helps present them in an alternative format that can potentially be more easily communicated to clinicians, patients, and the public at large,” explained Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, both in Boston.
The impact of intensive BP control on residual survival was magnified in patients who were younger, since they intrinsically have a longer expected survival and will apply the antihypertensive regimen over a longer period. For example, the actuarial analysis concluded that the mean survival benefit of starting intensive BP lowering, rather than settling for a target systolic BP of less than 140 mm Hg starting at age 50 years, was 3 additional years of life, as compared with 1.1 additional years in 65-year-olds and 0.5 years in patients aged 85 years or older. The same approach can be applied to patients at any individual age from 50 to 95 years at the time of enrollment.
“This is very helpful in conveying messages to individual patients. Often if you tell a patient: ‘Your risk is going to go down by 27%,’ it’s tough for them to recognize what the baseline is and if that actually applied to them. So this may personalize that decision-making conversation,” according to the cardiologist.
One audience member commented that this SPRINT analysis might actually underestimate the true survival advantage of intensive BP lowering. He noted that SPRINT, which was halted after an average of 3.3 years, didn’t show a significant benefit for intensive BP lowering in terms of stroke reduction, whereas the ACCORD trial did, but that benefit didn’t occur until after 3 years into the study (Hypertension. 2018 Aug;72[2]:323-30).
Dr. Vaduganathan conceded that’s a limitation of his analysis.
“The assumption we’ve used is that long-term cardiovascular benefits are going to be as seen in the trial, but since SPRINT was stopped early, some benefits may be exaggerated and some may not have been observed yet,” he agreed.
Another audience member observed, “I think a lot of patients will think: ‘Okay, you’re tacking on a year at the end, when I’m going to be 89 and demented.’ The National Institute on Aging is focusing a lot more now on nondisabled life expectancy or healthy life expectancy.’”
Dr. Vaduganathan offered a degree of reassurance on this score. Because of time limitations, he said, he only presented the life expectancy results. But he and his coworkers have performed the same actuarial analysis of the SPRINT data for other endpoints related to freedom from various forms of disease or disability and found a consistent effect: Intensive BP control was associated with a longer time to onset of morbidity.
SPRINT was sponsored primarily by the National Heart, Lung, and Blood Institute. Dr. Vaduganathan reported that he receives research support from/and or serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer, Boehringer Ingelheim, and Relypsa.
SOURCE: Vaduganathan M et al. AHA 2019, Abstract MDP233.
REPORTING FROM AHA 2019
Drop in flu activity may not signal seasonal peak
A key indicator of flu activity dropped but remains high, but measures of severity have not yet shown any unusual increases, according to the Centers for Disease Control and Prevention.
Patients with influenza-like illness (ILI) made up an estimated 5.8% of the visits to outpatient providers during the week ending Jan. 4, and that’s a decline from 7.0% for the last full week of 2019, the CDC’s influenza division reported.
That 7.0% outpatient ILI visit rate was the highest seen in December since 2003, but “hospitalization rates and percent of deaths due to pneumonia and influenza remain low,” the influenza division said in its weekly report.
Influenza B/Victoria and influenza A(H1N1)pdm09 viruses have been the predominant strains so far this season, and they “are more likely to affect children and younger adults than the elderly. Because the majority of hospitalizations and deaths occur among people age 65 and older, with fewer illnesses among that group, we expect, on a population level, to see less impact in flu-related hospitalizations and deaths,” the CDC said.
Last year, there was a similar drop in the outpatient ILI rate in early January after visits rose through December. The rate then increased for another 5 weeks before peaking at 5.0% in February. A similar pattern also occurred during the 2016-2017 and 2015-2016 seasons, CDC data show.
The nationwide ILI hospitalization rate, which is cumulative through the season, was up to 14.6 per 100,000 population for the week ending Jan. 4, the CDC said. Here are the corresponding rates for each of the last five seasons:
- 11.6 (2018-2019).
- 30.5 (2017-2018).
- 12.2 (2016-2017).
- 1.8 (2015-2016).
- 38.3 (2014-2015).
There were five new ILI-related pediatric deaths reported for the week ending Jan. 4, two of which occurred the week before. The total is now up to 32 for the 2019-2020 season, the CDC said in the weekly report. Last season, there were 21 pediatric deaths through the first January report, compared with 42 during the 2017-2018 season and 13 in 2016-2017.
A key indicator of flu activity dropped but remains high, but measures of severity have not yet shown any unusual increases, according to the Centers for Disease Control and Prevention.
Patients with influenza-like illness (ILI) made up an estimated 5.8% of the visits to outpatient providers during the week ending Jan. 4, and that’s a decline from 7.0% for the last full week of 2019, the CDC’s influenza division reported.
That 7.0% outpatient ILI visit rate was the highest seen in December since 2003, but “hospitalization rates and percent of deaths due to pneumonia and influenza remain low,” the influenza division said in its weekly report.
Influenza B/Victoria and influenza A(H1N1)pdm09 viruses have been the predominant strains so far this season, and they “are more likely to affect children and younger adults than the elderly. Because the majority of hospitalizations and deaths occur among people age 65 and older, with fewer illnesses among that group, we expect, on a population level, to see less impact in flu-related hospitalizations and deaths,” the CDC said.
Last year, there was a similar drop in the outpatient ILI rate in early January after visits rose through December. The rate then increased for another 5 weeks before peaking at 5.0% in February. A similar pattern also occurred during the 2016-2017 and 2015-2016 seasons, CDC data show.
The nationwide ILI hospitalization rate, which is cumulative through the season, was up to 14.6 per 100,000 population for the week ending Jan. 4, the CDC said. Here are the corresponding rates for each of the last five seasons:
- 11.6 (2018-2019).
- 30.5 (2017-2018).
- 12.2 (2016-2017).
- 1.8 (2015-2016).
- 38.3 (2014-2015).
There were five new ILI-related pediatric deaths reported for the week ending Jan. 4, two of which occurred the week before. The total is now up to 32 for the 2019-2020 season, the CDC said in the weekly report. Last season, there were 21 pediatric deaths through the first January report, compared with 42 during the 2017-2018 season and 13 in 2016-2017.
A key indicator of flu activity dropped but remains high, but measures of severity have not yet shown any unusual increases, according to the Centers for Disease Control and Prevention.
Patients with influenza-like illness (ILI) made up an estimated 5.8% of the visits to outpatient providers during the week ending Jan. 4, and that’s a decline from 7.0% for the last full week of 2019, the CDC’s influenza division reported.
That 7.0% outpatient ILI visit rate was the highest seen in December since 2003, but “hospitalization rates and percent of deaths due to pneumonia and influenza remain low,” the influenza division said in its weekly report.
Influenza B/Victoria and influenza A(H1N1)pdm09 viruses have been the predominant strains so far this season, and they “are more likely to affect children and younger adults than the elderly. Because the majority of hospitalizations and deaths occur among people age 65 and older, with fewer illnesses among that group, we expect, on a population level, to see less impact in flu-related hospitalizations and deaths,” the CDC said.
Last year, there was a similar drop in the outpatient ILI rate in early January after visits rose through December. The rate then increased for another 5 weeks before peaking at 5.0% in February. A similar pattern also occurred during the 2016-2017 and 2015-2016 seasons, CDC data show.
The nationwide ILI hospitalization rate, which is cumulative through the season, was up to 14.6 per 100,000 population for the week ending Jan. 4, the CDC said. Here are the corresponding rates for each of the last five seasons:
- 11.6 (2018-2019).
- 30.5 (2017-2018).
- 12.2 (2016-2017).
- 1.8 (2015-2016).
- 38.3 (2014-2015).
There were five new ILI-related pediatric deaths reported for the week ending Jan. 4, two of which occurred the week before. The total is now up to 32 for the 2019-2020 season, the CDC said in the weekly report. Last season, there were 21 pediatric deaths through the first January report, compared with 42 during the 2017-2018 season and 13 in 2016-2017.
Treatment of heart failure with preserved ejection fraction is a work in progress
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
LOS ANGELES – When it comes to the optimal treatment of patients with heart failure with preserved ejection fraction and diabetes, cardiologists like Mark T. Kearney, MB ChB, MD, remain stumped.
“Over the years, the diagnosis of heart failure with preserved ejection fraction has been notoriously difficult [to treat], controversial, and ultimately involves aggressive catheterization of the heart to assess diastolic dysfunction, complex echocardiography, and invasive tests,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “These patients have an ejection fraction of over 50% and classic signs and symptoms of heart failure. Studies of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers have been unsuccessful in this group of patients. We’re at the beginning of a journey in understanding this disorder, and it’s important, because more and more patients present to us with signs and symptoms of heart failure with an ejection fraction greater than 50%.”
In a recent analysis of 1,797 patients with chronic heart failure, Dr. Kearney, British Heart Foundation Professor of Cardiovascular and Diabetes Research at the Leeds (England) Institute of Cardiovascular and Metabolic Medicine, and colleagues examined whether beta-blockers and ACE inhibitors were associated with differential effects on mortality in patients with and without diabetes (Diabetes Care. 2018;41:136-42). Mean follow-up was 4 years.
For the ACE inhibitor component of the trial, the researchers correlated the dose of ramipril to outcomes and found that each milligram increase of ramipril reduced the risk of death by about 3%. “In the nondiabetic patients who did not receive an ACE inhibitor, mortality was about 60% – worse than most cancers,” Dr. Kearney said. “In patients with diabetes, there was a similar pattern. If you didn’t get an ACE inhibitor, mortality was 70%. So, if you get patients on an optimal dose of an ACE inhibitor, you improve their mortality substantially, whether they have diabetes or not.”
The beta-blocker component of the trial yielded similar results. “Among patients who did not receive a beta-blocker, the mortality was about 70% at 5 years – really terrible,” he said. “Every milligram of bisoprolol was associated with a reduction in mortality of about 9%. So, if a patient gets on an optimal dose of a beta-blocker and they have diabetes, it’s associated with prolongation of life over a year.”
Dr. Kearney said that patients often do not want to take an increased dose of a beta-blocker because of concerns about side effects, such as tiredness. “They ask me what the side effects of an increased dose would be. My answer is: ‘It will make you live longer.’ Usually, they’ll respond by agreeing to have a little bit more of the beta-blocker. The message here is, if you have a patient with ejection fraction heart failure and diabetes, get them on the optimal dose of a beta-blocker, even at the expense of an ACE inhibitor.”
In 2016, the European Society of Cardiology introduced guidelines for physicians to make a diagnosis of heart failure with preserved ejection fraction. The guidelines mandate that a diagnosis requires signs and symptoms of heart failure, elevated levels of natriuretic peptide, and echocardiographic abnormalities of cardiac structure and/or function in the presence of a left ventricular ejection fraction of 50% or more (Eur J Heart Fail. 2016;18[8]:891-975).
“Signs and symptoms of heart failure, elevated BNP [brain natriuretic peptide], and echocardiography allow us to make a diagnosis of heart failure with preserved ejection fraction,” Dr. Kearney, who is also dean of the Leeds University School of Medicine. “But we don’t know the outcome of these patients, we don’t know how to treat them, and we don’t know the impact on hospitalizations.”
In a large, unpublished cohort study conducted at Leeds, Dr. Kearney and colleagues evaluated how many patients met criteria for heart failure with reduced ejection fraction or heart failure with preserved ejection fraction after undergoing a BNP measurement. Ultimately, 959 patients met criteria. After assessment, 23% had no heart failure, 44% had heart failure with preserved ejection fraction, and 33% had heart failure with reduced ejection fraction. They found that patients with preserved ejection fraction were older (mean age, 84 years); were more likely to be female; and had less ischemia, less diabetes, and more hypertension. In addition, patients with preserved ejection fraction had significantly better survival than patients with reduced ejection fraction over 5 years follow-up.
“What was really interesting were the findings related to hospitalization,” he said. “All 959 patients accounted for 20,517 days in the hospital over 5 years, which is the equivalent of 1 patient occupying a hospital bed for 56 years. This disorder [heart failure with preserved ejection fraction], despite having a lower mortality than heart failure with reduced ejection fraction, leads to a significant burden on health care systems.”
Among patients with preserved ejection fraction, 82% were hospitalized for a noncardiovascular cause, 6.9% because of heart failure, and 11% were caused by other cardiovascular causes. Most of the hospital admissions were because of chest infections, falls, and other frailty-linked causes. “This link between systemic frailty and heart failure with preserved ejection fraction warrants further investigation,” Dr. Kearney said. “This is a major burden on patient hospital care.”
When the researchers examined outcomes in patients with and without diabetes, those with diabetes were younger, more likely to be male, and have a higher body mass index. They found that, in the presence of diabetes, mortality was increased in heart failure with preserved and reduced ejection fraction. “So, even at the age of 81 or 82, diabetes changes the pathophysiology of mortality in what was previously believed to be a benign disease,” he said.
In a subset analysis of patients with and without diabetes who were not taking a beta-blocker, there did not seem to be increased sympathetic activation in the patients with diabetes and heart failure with preserved ejection fraction, nor a difference in heart rate between the nondiabetic patients and patients with diabetes. However, among patients with heart failure with reduced ejection fraction, those with diabetes had an increased heart rate.
“Is heart failure with preserved ejection fraction in diabetes benign? I think the answer is no,” Dr. Kearney said. “It increases hospitalization and is a major burden on health care systems. What should we do? We deal with comorbidity and fall risk. It’s good old-fashioned doctoring, really. We address frailty and respiratory tract infections, but the key thing here is that we need more research.”
Dr. Kearney reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM WCIRDC 2019
ID consult for Candida bloodstream infections can reduce mortality risk
findings from a large retrospective study suggest.
Mortality attributable to Candida bloodstream infection ranges between 15% and 47%, and delay in initiation of appropriate treatment has been associated with increased mortality. Previous small studies showed that ID consultation has conferred benefits to patients with Candida bloodstream infections. Carlos Mejia-Chew, MD, and colleagues from Washington University, St. Louis, sought to explore this further by performing a retrospective, single-center cohort study of 1,691 patients aged 18 years or older with Candida bloodstream infection from 2002 to 2015. They analyzed demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation in order to compare 90-day all-cause mortality between individuals with and without an ID consultation.
They found that those patients who received an ID consult for a Candida bloodstream infection had a significantly lower 90-day mortality rate than did those who did not (29% vs. 51%).
With a model using inverse weighting by the propensity score, they found that ID consultation was associated with a hazard ratio of 0.81 for mortality (95% confidence interval, 0.73-0.91; P less than .0001). In the ID consultation group, the median duration of antifungal therapy was significantly longer (18 vs. 14 days; P less than .0001); central-line removal was significantly more common (76% vs. 59%; P less than .0001); echocardiography use was more frequent (57% vs. 33%; P less than .0001); and ophthalmological examinations were performed more often (53% vs. 17%; P less than .0001). Importantly, fewer patients in the ID consultation group were untreated (2% vs. 14%; P less than .0001).
In an accompanying commentary, Katrien Lagrou, MD, and Eric Van Wijngaerden, MD, of the department of microbiology, immunology and transplantation, University Hospitals Leuven (Belgium) stated: “We think that the high proportion of patients (14%) with a Candida bloodstream infection who did not receive any antifungal treatment and did not have an infectious disease consultation is a particularly alarming finding. ... Ninety-day mortality in these untreated patients was high (67%).”
“We believe every hospital should have an expert management strategy addressing all individual cases of candidaemia. The need for such expert management should be incorporated in all future candidaemia management guidelines,” they concluded.
The study was funded by the Astellas Global Development Pharma, the Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality. Several of the authors had financial connections to Astellas Global Development or other pharmaceutical companies. Dr. Lagrou and Dr. Van Wijngaerden both reported receiving personal fees and nonfinancial support from a number of pharmaceutical companies, but all outside the scope of the study.
SOURCE: Mejia-Chew C et al. Lancet Infect Dis. 2019;19:1336-44.
findings from a large retrospective study suggest.
Mortality attributable to Candida bloodstream infection ranges between 15% and 47%, and delay in initiation of appropriate treatment has been associated with increased mortality. Previous small studies showed that ID consultation has conferred benefits to patients with Candida bloodstream infections. Carlos Mejia-Chew, MD, and colleagues from Washington University, St. Louis, sought to explore this further by performing a retrospective, single-center cohort study of 1,691 patients aged 18 years or older with Candida bloodstream infection from 2002 to 2015. They analyzed demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation in order to compare 90-day all-cause mortality between individuals with and without an ID consultation.
They found that those patients who received an ID consult for a Candida bloodstream infection had a significantly lower 90-day mortality rate than did those who did not (29% vs. 51%).
With a model using inverse weighting by the propensity score, they found that ID consultation was associated with a hazard ratio of 0.81 for mortality (95% confidence interval, 0.73-0.91; P less than .0001). In the ID consultation group, the median duration of antifungal therapy was significantly longer (18 vs. 14 days; P less than .0001); central-line removal was significantly more common (76% vs. 59%; P less than .0001); echocardiography use was more frequent (57% vs. 33%; P less than .0001); and ophthalmological examinations were performed more often (53% vs. 17%; P less than .0001). Importantly, fewer patients in the ID consultation group were untreated (2% vs. 14%; P less than .0001).
In an accompanying commentary, Katrien Lagrou, MD, and Eric Van Wijngaerden, MD, of the department of microbiology, immunology and transplantation, University Hospitals Leuven (Belgium) stated: “We think that the high proportion of patients (14%) with a Candida bloodstream infection who did not receive any antifungal treatment and did not have an infectious disease consultation is a particularly alarming finding. ... Ninety-day mortality in these untreated patients was high (67%).”
“We believe every hospital should have an expert management strategy addressing all individual cases of candidaemia. The need for such expert management should be incorporated in all future candidaemia management guidelines,” they concluded.
The study was funded by the Astellas Global Development Pharma, the Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality. Several of the authors had financial connections to Astellas Global Development or other pharmaceutical companies. Dr. Lagrou and Dr. Van Wijngaerden both reported receiving personal fees and nonfinancial support from a number of pharmaceutical companies, but all outside the scope of the study.
SOURCE: Mejia-Chew C et al. Lancet Infect Dis. 2019;19:1336-44.
findings from a large retrospective study suggest.
Mortality attributable to Candida bloodstream infection ranges between 15% and 47%, and delay in initiation of appropriate treatment has been associated with increased mortality. Previous small studies showed that ID consultation has conferred benefits to patients with Candida bloodstream infections. Carlos Mejia-Chew, MD, and colleagues from Washington University, St. Louis, sought to explore this further by performing a retrospective, single-center cohort study of 1,691 patients aged 18 years or older with Candida bloodstream infection from 2002 to 2015. They analyzed demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation in order to compare 90-day all-cause mortality between individuals with and without an ID consultation.
They found that those patients who received an ID consult for a Candida bloodstream infection had a significantly lower 90-day mortality rate than did those who did not (29% vs. 51%).
With a model using inverse weighting by the propensity score, they found that ID consultation was associated with a hazard ratio of 0.81 for mortality (95% confidence interval, 0.73-0.91; P less than .0001). In the ID consultation group, the median duration of antifungal therapy was significantly longer (18 vs. 14 days; P less than .0001); central-line removal was significantly more common (76% vs. 59%; P less than .0001); echocardiography use was more frequent (57% vs. 33%; P less than .0001); and ophthalmological examinations were performed more often (53% vs. 17%; P less than .0001). Importantly, fewer patients in the ID consultation group were untreated (2% vs. 14%; P less than .0001).
In an accompanying commentary, Katrien Lagrou, MD, and Eric Van Wijngaerden, MD, of the department of microbiology, immunology and transplantation, University Hospitals Leuven (Belgium) stated: “We think that the high proportion of patients (14%) with a Candida bloodstream infection who did not receive any antifungal treatment and did not have an infectious disease consultation is a particularly alarming finding. ... Ninety-day mortality in these untreated patients was high (67%).”
“We believe every hospital should have an expert management strategy addressing all individual cases of candidaemia. The need for such expert management should be incorporated in all future candidaemia management guidelines,” they concluded.
The study was funded by the Astellas Global Development Pharma, the Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality. Several of the authors had financial connections to Astellas Global Development or other pharmaceutical companies. Dr. Lagrou and Dr. Van Wijngaerden both reported receiving personal fees and nonfinancial support from a number of pharmaceutical companies, but all outside the scope of the study.
SOURCE: Mejia-Chew C et al. Lancet Infect Dis. 2019;19:1336-44.
FROM LANCET: INFECTIOUS DISEASES