The Hospitalist

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Southern Denmark, Odense, said that the European Medicines Agency has noted a few postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving this drug, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Graves disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.
 

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Southern Denmark, Odense, said that the European Medicines Agency has noted a few postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving this drug, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Graves disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.
 

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Southern Denmark, Odense, said that the European Medicines Agency has noted a few postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving this drug, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Graves disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.
 

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

“Do you vape?” may be one of the most important questions health care can providers can ask patients who present with respiratory symptoms this winter.

mauro grigollo/Thinkstock

Vaping-related lung injuries cause symptoms such as fever, cough, headache, and fatigue, making it challenging to differentiate them from influenza or respiratory infections, according to the Centers for Disease Control and Prevention.

Accordingly, providers need to ask patients with respiratory, gastrointestinal, or constitutional symptoms about their use of e-cigarette or vaping products, according to one several new CDC recommendations that appear in the Morbidity and Mortality Weekly Review.

“E-cigarette or vaping product use–associated lung injury (EVALI) remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment,” the CDC report reads.

As of Nov. 13, there have been 2,172 cases of EVALI reported to CDC, of which 42 (1.9%) have been fatal. Most of the patients with EVALI have been white (79%), male (68%), and under the age of 35 years (77%), according to CDC data.

Although vitamin E acetate was recently implicated as a potential cause of EVALI, the agency said evidence is “not sufficient” at this point in their investigation to rule out other chemicals of potential concern.

“Many different substances and product sources are still under investigation, and it might be that there is more than one cause of this outbreak,” CDC said.

Further recommendations

Beyond asking about vape use, providers should evaluate suspected EVALI with pulse oximetry and chest imaging, and should consider outpatient management for patients who are clinically stable, according to the recommendations.

The agency said influenza testing should be “strongly considered,” especially during influenza season, given that EVALI is a diagnosis of exclusion and that it may co-occur with other respiratory illnesses. Antimicrobials (including antivirals) should be given as warranted, they added.

Corticosteroids may be helpful in treating EVALI, but may worsen respiratory infections typically seen in outpatients, and so should be prescribed with caution in the outpatient setting, the CDC recommended.

Behavioral counseling, addiction treatment services, and Food and Drug Administration–approved cessation medications are recommended to help patients quit vaping or e-cigarette products, CDC said.

Health care providers should emphasize the importance of an annual flu shot for all patients 6 months of age or older, including those who use e-cigarette or vaping products, according to the agency.

“It is not known whether patients with EVALI are at higher risk for severe complications of influenza or other respiratory infections,” the report reads.

Blame it on vitamin E? THC? Other?

The report details how, as previously reported, vitamin E acetate was detected in bronchoalveolar lavage fluid samples from 29 patients with EVALI. Although other chemicals could contribute to EVALI, that finding provided “direct evidence” of vitamin E acetate at the primary site of injury, according to CDC.

Most patients with EVALI, 83%, have reported using a tetrahydrocannabinol (THC)-containing e-cigarette or vaping product, according to CDC, while 61% reported using a nicotine-containing product.

Based on that, CDC recommended that people avoid using THC-containing products. However, the agency cautioned that the specific cause or causes of EVALI remain to be elucidated.

“The only way for persons to assure that they are not at risk is to consider refraining from use of all e-cigarette, or vaping, products while this investigation continues,” CDC said in the report.

The need for this additional clinical guidance was assessed in anticipation of the seasonal uptick in influenza and other respiratory infections, according to the CDC, which said the recommendations were based in part on individual clinical perspectives from nine national experts who participated in a previously published clinical guidance on managing patients with EVALI.

SOURCES: Jatlaoui TC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e2; Chatham-Stephens K et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e1.

“Do you vape?” may be one of the most important questions health care can providers can ask patients who present with respiratory symptoms this winter.

mauro grigollo/Thinkstock

Vaping-related lung injuries cause symptoms such as fever, cough, headache, and fatigue, making it challenging to differentiate them from influenza or respiratory infections, according to the Centers for Disease Control and Prevention.

Accordingly, providers need to ask patients with respiratory, gastrointestinal, or constitutional symptoms about their use of e-cigarette or vaping products, according to one several new CDC recommendations that appear in the Morbidity and Mortality Weekly Review.

“E-cigarette or vaping product use–associated lung injury (EVALI) remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment,” the CDC report reads.

As of Nov. 13, there have been 2,172 cases of EVALI reported to CDC, of which 42 (1.9%) have been fatal. Most of the patients with EVALI have been white (79%), male (68%), and under the age of 35 years (77%), according to CDC data.

Although vitamin E acetate was recently implicated as a potential cause of EVALI, the agency said evidence is “not sufficient” at this point in their investigation to rule out other chemicals of potential concern.

“Many different substances and product sources are still under investigation, and it might be that there is more than one cause of this outbreak,” CDC said.

Further recommendations

Beyond asking about vape use, providers should evaluate suspected EVALI with pulse oximetry and chest imaging, and should consider outpatient management for patients who are clinically stable, according to the recommendations.

The agency said influenza testing should be “strongly considered,” especially during influenza season, given that EVALI is a diagnosis of exclusion and that it may co-occur with other respiratory illnesses. Antimicrobials (including antivirals) should be given as warranted, they added.

Corticosteroids may be helpful in treating EVALI, but may worsen respiratory infections typically seen in outpatients, and so should be prescribed with caution in the outpatient setting, the CDC recommended.

Behavioral counseling, addiction treatment services, and Food and Drug Administration–approved cessation medications are recommended to help patients quit vaping or e-cigarette products, CDC said.

Health care providers should emphasize the importance of an annual flu shot for all patients 6 months of age or older, including those who use e-cigarette or vaping products, according to the agency.

“It is not known whether patients with EVALI are at higher risk for severe complications of influenza or other respiratory infections,” the report reads.

Blame it on vitamin E? THC? Other?

The report details how, as previously reported, vitamin E acetate was detected in bronchoalveolar lavage fluid samples from 29 patients with EVALI. Although other chemicals could contribute to EVALI, that finding provided “direct evidence” of vitamin E acetate at the primary site of injury, according to CDC.

Most patients with EVALI, 83%, have reported using a tetrahydrocannabinol (THC)-containing e-cigarette or vaping product, according to CDC, while 61% reported using a nicotine-containing product.

Based on that, CDC recommended that people avoid using THC-containing products. However, the agency cautioned that the specific cause or causes of EVALI remain to be elucidated.

“The only way for persons to assure that they are not at risk is to consider refraining from use of all e-cigarette, or vaping, products while this investigation continues,” CDC said in the report.

The need for this additional clinical guidance was assessed in anticipation of the seasonal uptick in influenza and other respiratory infections, according to the CDC, which said the recommendations were based in part on individual clinical perspectives from nine national experts who participated in a previously published clinical guidance on managing patients with EVALI.

SOURCES: Jatlaoui TC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e2; Chatham-Stephens K et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e1.

“Do you vape?” may be one of the most important questions health care can providers can ask patients who present with respiratory symptoms this winter.

mauro grigollo/Thinkstock

Vaping-related lung injuries cause symptoms such as fever, cough, headache, and fatigue, making it challenging to differentiate them from influenza or respiratory infections, according to the Centers for Disease Control and Prevention.

Accordingly, providers need to ask patients with respiratory, gastrointestinal, or constitutional symptoms about their use of e-cigarette or vaping products, according to one several new CDC recommendations that appear in the Morbidity and Mortality Weekly Review.

“E-cigarette or vaping product use–associated lung injury (EVALI) remains a diagnosis of exclusion because, at present, no specific test or marker exists for its diagnosis, and evaluation should be guided by clinical judgment,” the CDC report reads.

As of Nov. 13, there have been 2,172 cases of EVALI reported to CDC, of which 42 (1.9%) have been fatal. Most of the patients with EVALI have been white (79%), male (68%), and under the age of 35 years (77%), according to CDC data.

Although vitamin E acetate was recently implicated as a potential cause of EVALI, the agency said evidence is “not sufficient” at this point in their investigation to rule out other chemicals of potential concern.

“Many different substances and product sources are still under investigation, and it might be that there is more than one cause of this outbreak,” CDC said.

Further recommendations

Beyond asking about vape use, providers should evaluate suspected EVALI with pulse oximetry and chest imaging, and should consider outpatient management for patients who are clinically stable, according to the recommendations.

The agency said influenza testing should be “strongly considered,” especially during influenza season, given that EVALI is a diagnosis of exclusion and that it may co-occur with other respiratory illnesses. Antimicrobials (including antivirals) should be given as warranted, they added.

Corticosteroids may be helpful in treating EVALI, but may worsen respiratory infections typically seen in outpatients, and so should be prescribed with caution in the outpatient setting, the CDC recommended.

Behavioral counseling, addiction treatment services, and Food and Drug Administration–approved cessation medications are recommended to help patients quit vaping or e-cigarette products, CDC said.

Health care providers should emphasize the importance of an annual flu shot for all patients 6 months of age or older, including those who use e-cigarette or vaping products, according to the agency.

“It is not known whether patients with EVALI are at higher risk for severe complications of influenza or other respiratory infections,” the report reads.

Blame it on vitamin E? THC? Other?

The report details how, as previously reported, vitamin E acetate was detected in bronchoalveolar lavage fluid samples from 29 patients with EVALI. Although other chemicals could contribute to EVALI, that finding provided “direct evidence” of vitamin E acetate at the primary site of injury, according to CDC.

Most patients with EVALI, 83%, have reported using a tetrahydrocannabinol (THC)-containing e-cigarette or vaping product, according to CDC, while 61% reported using a nicotine-containing product.

Based on that, CDC recommended that people avoid using THC-containing products. However, the agency cautioned that the specific cause or causes of EVALI remain to be elucidated.

“The only way for persons to assure that they are not at risk is to consider refraining from use of all e-cigarette, or vaping, products while this investigation continues,” CDC said in the report.

The need for this additional clinical guidance was assessed in anticipation of the seasonal uptick in influenza and other respiratory infections, according to the CDC, which said the recommendations were based in part on individual clinical perspectives from nine national experts who participated in a previously published clinical guidance on managing patients with EVALI.

SOURCES: Jatlaoui TC et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e2; Chatham-Stephens K et al. MMWR Morb Mortal Wkly Rep. 2019 Nov 19. doi. 10.15585/mmwr.mm6846e1.

It’s always important for everyone to remember why we document things in the chart so that we are on the same page and ultimately do what is best for the patient. We document for insurance companies to prove the need for hospitalization, for legal purposes, and for other clinicians – to clearly communicate the acuity of each patient.

One of the diagnoses that we can often forget to use is acute respiratory failure. Documenting acute respiratory failure matters, regardless if it is, or is not, the primary diagnosis; it increases the estimated Length of Stay (LOS), Severity of Illness (SOI), and Risk of Mortality (ROM). This diagnosis adds an additional degree of specificity to patients with pneumonia, pleural effusions, chronic obstructive pulmonary disease (COPD) exacerbations, etc. While we may be hesitant to document this (perhaps feeling that this applies only to patients who are intubated in the ICU), the reader will hopefully have more confidence using it after reviewing the diagnostic criteria.

Acute respiratory failure can stem from impaired oxygenation or impaired ventilation. The following are some examples that follow these principles:

• Impaired oxygenation. Can be seen in pneumonia, pulmonary edema, and pulmonary embolism, and can present as a low O₂ saturation or a low pO₂ on an arterial blood gas (ABG) test.
• Impaired ventilation. Can be seen in COPD or asthma where there is increased effort to ventilate the lungs, which can lead to impaired CO₂ exchange and subsequent acidosis.

One needs to have two of the following three criteria to make a formal diagnosis of acute respiratory failure:

• pO₂ less than 60 mm Hg (hypoxemia).
• pCO₂ greater than 50 mm Hg (hypercapnia) with pH less than 7.35.
• Signs and symptoms of acute respiratory distress.

One may think that it would be difficult to meet criteria without an ABG. Although an ABG is the standard, a patient meets criteria 1 without a blood gas if an oxygen saturation less than or equal to 90% is documented. Therefore, in most cases, if you have a documented oxygen saturation less than or equal to 90% on room air with a physical exam showing signs of respiratory distress, your patient will qualify for the diagnosis of acute respiratory failure. This negates the need to always have an ABG.

It is important to document the symptoms and physical exam findings that go along with the diagnosis. Patients should have tachypnea with a respiratory rate (RR) greater than 20 or a decreased rate less than 10. They may have wheezing, difficulty moving air, nasal flaring, and accessory muscle use. All of these findings are extremely helpful to validate the diagnosis and would make it extremely difficult for it to be rejected by a biller or insurance company.

These patients are often given supplemental oxygen (nasal cannula, Venturi mask, non-rebreather) and other treatments including steroids, inhaled bronchodilators, mucolytics, and respiratory therapy. Documenting these interventions in your plans can assist reviewers trying to understand your thought process in the treatment of the patient. If your patient has to be initiated on bilevel positive airway pressure (i.e. – the patient was not on BIPAP at home, but needed to be started because of his/her respiratory status), this almost always means they have acute respiratory failure.

In the two tables accompanying this article, we see some examples of how documenting acute respiratory failure can improve LOS, ROM, SOI, and reimbursement. The number at the top is based off of a specific DRG (Diagnosis Related Group) that is used by coders.

Let’s say we have a 58-year-old male presenting with chest pain, shortness of breath, and concern for unstable angina. Given his symptoms, he is being taken to the cardiac catheterization lab. If we note only that he was hypoxic and required 3L for an O₂ saturation of 94%, one can see the ROM, SOI, estimated LOS, and reimbursement in the first column. However, if we write that his oxygen saturation on room air is 87%, he is using intercostal muscles to breathe, and he has marked dyspnea with conversation, we can say that he has acute respiratory failure. Making this distinction increases his expected LOS by almost 4 days and nearly doubles reimbursement.



For the second example, we have an 81-year-old female with diabetes type 2, hypertension, and chronic systolic congestive heart failure who presents with an acute systolic CHF exacerbation. The patient is saturating 85% on room air, has tachypnea (RR 34), and was given large doses of intravenous furosemide in the emergency department. She is stabilized with improvement in her respiratory rate and can go to the floor, but by documenting that this was acute respiratory failure, one can again see the significant improvements in the projected LOS, ROM, and reimbursement as opposed to documenting hypoxia. This has huge implications for our hospitals, and we should continue to strive to document this as clearly as possible.

 

Key take-home points for hospitalists

• Document accurately, including any comorbid conditions and major comorbid conditions that are applicable.
• Acute respiratory failure comes from impaired oxygenation, impaired ventilation, or both.
• One needs to document two of the three criteria to formally diagnose acute respiratory failure: pO₂ less than 60 mm Hg (or room air oxygen saturation less than or equal to 90%), pCO₂ greater than 50 mm Hg with pH less than 7.35, and signs/symptoms of respiratory distress.
• Document physical exam findings that correlate with acute respiratory failure (RR greater than 20 or less than 10, wheezing, nasal flaring, accessory muscle use, etc).
• If your patient has to be initiated on BIPAP (i.e. – the patient was not on BIPAP at home, but needed to be started because of his/her respiratory status), they likely have acute respiratory failure.

Dr. DeCaro is a hospitalist and medical director for care coordination at Emory University in Atlanta.

It’s always important for everyone to remember why we document things in the chart so that we are on the same page and ultimately do what is best for the patient. We document for insurance companies to prove the need for hospitalization, for legal purposes, and for other clinicians – to clearly communicate the acuity of each patient.

One of the diagnoses that we can often forget to use is acute respiratory failure. Documenting acute respiratory failure matters, regardless if it is, or is not, the primary diagnosis; it increases the estimated Length of Stay (LOS), Severity of Illness (SOI), and Risk of Mortality (ROM). This diagnosis adds an additional degree of specificity to patients with pneumonia, pleural effusions, chronic obstructive pulmonary disease (COPD) exacerbations, etc. While we may be hesitant to document this (perhaps feeling that this applies only to patients who are intubated in the ICU), the reader will hopefully have more confidence using it after reviewing the diagnostic criteria.

Acute respiratory failure can stem from impaired oxygenation or impaired ventilation. The following are some examples that follow these principles:

• Impaired oxygenation. Can be seen in pneumonia, pulmonary edema, and pulmonary embolism, and can present as a low O₂ saturation or a low pO₂ on an arterial blood gas (ABG) test.
• Impaired ventilation. Can be seen in COPD or asthma where there is increased effort to ventilate the lungs, which can lead to impaired CO₂ exchange and subsequent acidosis.

One needs to have two of the following three criteria to make a formal diagnosis of acute respiratory failure:

• pO₂ less than 60 mm Hg (hypoxemia).
• pCO₂ greater than 50 mm Hg (hypercapnia) with pH less than 7.35.
• Signs and symptoms of acute respiratory distress.

One may think that it would be difficult to meet criteria without an ABG. Although an ABG is the standard, a patient meets criteria 1 without a blood gas if an oxygen saturation less than or equal to 90% is documented. Therefore, in most cases, if you have a documented oxygen saturation less than or equal to 90% on room air with a physical exam showing signs of respiratory distress, your patient will qualify for the diagnosis of acute respiratory failure. This negates the need to always have an ABG.

It is important to document the symptoms and physical exam findings that go along with the diagnosis. Patients should have tachypnea with a respiratory rate (RR) greater than 20 or a decreased rate less than 10. They may have wheezing, difficulty moving air, nasal flaring, and accessory muscle use. All of these findings are extremely helpful to validate the diagnosis and would make it extremely difficult for it to be rejected by a biller or insurance company.

These patients are often given supplemental oxygen (nasal cannula, Venturi mask, non-rebreather) and other treatments including steroids, inhaled bronchodilators, mucolytics, and respiratory therapy. Documenting these interventions in your plans can assist reviewers trying to understand your thought process in the treatment of the patient. If your patient has to be initiated on bilevel positive airway pressure (i.e. – the patient was not on BIPAP at home, but needed to be started because of his/her respiratory status), this almost always means they have acute respiratory failure.

In the two tables accompanying this article, we see some examples of how documenting acute respiratory failure can improve LOS, ROM, SOI, and reimbursement. The number at the top is based off of a specific DRG (Diagnosis Related Group) that is used by coders.

Let’s say we have a 58-year-old male presenting with chest pain, shortness of breath, and concern for unstable angina. Given his symptoms, he is being taken to the cardiac catheterization lab. If we note only that he was hypoxic and required 3L for an O₂ saturation of 94%, one can see the ROM, SOI, estimated LOS, and reimbursement in the first column. However, if we write that his oxygen saturation on room air is 87%, he is using intercostal muscles to breathe, and he has marked dyspnea with conversation, we can say that he has acute respiratory failure. Making this distinction increases his expected LOS by almost 4 days and nearly doubles reimbursement.



For the second example, we have an 81-year-old female with diabetes type 2, hypertension, and chronic systolic congestive heart failure who presents with an acute systolic CHF exacerbation. The patient is saturating 85% on room air, has tachypnea (RR 34), and was given large doses of intravenous furosemide in the emergency department. She is stabilized with improvement in her respiratory rate and can go to the floor, but by documenting that this was acute respiratory failure, one can again see the significant improvements in the projected LOS, ROM, and reimbursement as opposed to documenting hypoxia. This has huge implications for our hospitals, and we should continue to strive to document this as clearly as possible.

 

Key take-home points for hospitalists

• Document accurately, including any comorbid conditions and major comorbid conditions that are applicable.
• Acute respiratory failure comes from impaired oxygenation, impaired ventilation, or both.
• One needs to document two of the three criteria to formally diagnose acute respiratory failure: pO₂ less than 60 mm Hg (or room air oxygen saturation less than or equal to 90%), pCO₂ greater than 50 mm Hg with pH less than 7.35, and signs/symptoms of respiratory distress.
• Document physical exam findings that correlate with acute respiratory failure (RR greater than 20 or less than 10, wheezing, nasal flaring, accessory muscle use, etc).
• If your patient has to be initiated on BIPAP (i.e. – the patient was not on BIPAP at home, but needed to be started because of his/her respiratory status), they likely have acute respiratory failure.

Dr. DeCaro is a hospitalist and medical director for care coordination at Emory University in Atlanta.

It’s always important for everyone to remember why we document things in the chart so that we are on the same page and ultimately do what is best for the patient. We document for insurance companies to prove the need for hospitalization, for legal purposes, and for other clinicians – to clearly communicate the acuity of each patient.

One of the diagnoses that we can often forget to use is acute respiratory failure. Documenting acute respiratory failure matters, regardless if it is, or is not, the primary diagnosis; it increases the estimated Length of Stay (LOS), Severity of Illness (SOI), and Risk of Mortality (ROM). This diagnosis adds an additional degree of specificity to patients with pneumonia, pleural effusions, chronic obstructive pulmonary disease (COPD) exacerbations, etc. While we may be hesitant to document this (perhaps feeling that this applies only to patients who are intubated in the ICU), the reader will hopefully have more confidence using it after reviewing the diagnostic criteria.

Acute respiratory failure can stem from impaired oxygenation or impaired ventilation. The following are some examples that follow these principles:

• Impaired oxygenation. Can be seen in pneumonia, pulmonary edema, and pulmonary embolism, and can present as a low O₂ saturation or a low pO₂ on an arterial blood gas (ABG) test.
• Impaired ventilation. Can be seen in COPD or asthma where there is increased effort to ventilate the lungs, which can lead to impaired CO₂ exchange and subsequent acidosis.

One needs to have two of the following three criteria to make a formal diagnosis of acute respiratory failure:

• pO₂ less than 60 mm Hg (hypoxemia).
• pCO₂ greater than 50 mm Hg (hypercapnia) with pH less than 7.35.
• Signs and symptoms of acute respiratory distress.

One may think that it would be difficult to meet criteria without an ABG. Although an ABG is the standard, a patient meets criteria 1 without a blood gas if an oxygen saturation less than or equal to 90% is documented. Therefore, in most cases, if you have a documented oxygen saturation less than or equal to 90% on room air with a physical exam showing signs of respiratory distress, your patient will qualify for the diagnosis of acute respiratory failure. This negates the need to always have an ABG.

It is important to document the symptoms and physical exam findings that go along with the diagnosis. Patients should have tachypnea with a respiratory rate (RR) greater than 20 or a decreased rate less than 10. They may have wheezing, difficulty moving air, nasal flaring, and accessory muscle use. All of these findings are extremely helpful to validate the diagnosis and would make it extremely difficult for it to be rejected by a biller or insurance company.

These patients are often given supplemental oxygen (nasal cannula, Venturi mask, non-rebreather) and other treatments including steroids, inhaled bronchodilators, mucolytics, and respiratory therapy. Documenting these interventions in your plans can assist reviewers trying to understand your thought process in the treatment of the patient. If your patient has to be initiated on bilevel positive airway pressure (i.e. – the patient was not on BIPAP at home, but needed to be started because of his/her respiratory status), this almost always means they have acute respiratory failure.

In the two tables accompanying this article, we see some examples of how documenting acute respiratory failure can improve LOS, ROM, SOI, and reimbursement. The number at the top is based off of a specific DRG (Diagnosis Related Group) that is used by coders.

Let’s say we have a 58-year-old male presenting with chest pain, shortness of breath, and concern for unstable angina. Given his symptoms, he is being taken to the cardiac catheterization lab. If we note only that he was hypoxic and required 3L for an O₂ saturation of 94%, one can see the ROM, SOI, estimated LOS, and reimbursement in the first column. However, if we write that his oxygen saturation on room air is 87%, he is using intercostal muscles to breathe, and he has marked dyspnea with conversation, we can say that he has acute respiratory failure. Making this distinction increases his expected LOS by almost 4 days and nearly doubles reimbursement.



For the second example, we have an 81-year-old female with diabetes type 2, hypertension, and chronic systolic congestive heart failure who presents with an acute systolic CHF exacerbation. The patient is saturating 85% on room air, has tachypnea (RR 34), and was given large doses of intravenous furosemide in the emergency department. She is stabilized with improvement in her respiratory rate and can go to the floor, but by documenting that this was acute respiratory failure, one can again see the significant improvements in the projected LOS, ROM, and reimbursement as opposed to documenting hypoxia. This has huge implications for our hospitals, and we should continue to strive to document this as clearly as possible.

 

Key take-home points for hospitalists

• Document accurately, including any comorbid conditions and major comorbid conditions that are applicable.
• Acute respiratory failure comes from impaired oxygenation, impaired ventilation, or both.
• One needs to document two of the three criteria to formally diagnose acute respiratory failure: pO₂ less than 60 mm Hg (or room air oxygen saturation less than or equal to 90%), pCO₂ greater than 50 mm Hg with pH less than 7.35, and signs/symptoms of respiratory distress.
• Document physical exam findings that correlate with acute respiratory failure (RR greater than 20 or less than 10, wheezing, nasal flaring, accessory muscle use, etc).
• If your patient has to be initiated on BIPAP (i.e. – the patient was not on BIPAP at home, but needed to be started because of his/her respiratory status), they likely have acute respiratory failure.

Dr. DeCaro is a hospitalist and medical director for care coordination at Emory University in Atlanta.

NEW YORK – Seven years after the formation of the first pulmonary embolism response team (PERT), more than 100 institutions have joined the PERT Consortium, which was created to guide care and research for this thrombotic complication, according to a status report at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

“Why are PERTs needed? Pulmonary embolism patients are like snowflakes. No two are the same,” explained Richard Channick, MD, director of the pulmonary vascular disease program, University of California, Los Angeles.

Patient variability is an issue because algorithms for pulmonary embolism (PE) often differ at the point of diagnosis, such as the emergency department or intensive are unit, according to Dr. Channick, who was present when the first PERT was created in 2012 at Massachusetts General Hospital (MGH) in Boston. In addition, treatment algorithms can seem complex at a time when patients are deteriorating quickly.

“The treatment algorithms always say consider this or consider that, and then you get a recommendation with a 2B grade of evidence. So what do you do?” Dr. Channick asked, “This has really been crying for an organized approach.”

PERTs were created to fill this need. In most centers, PERTs are organized to respond to a diagnosis of PE wherever it occurs in the hospital. The goal is rapid activation of a team of experts who can reach a single consensus recommendation.

At MGH and UCLA, a similar relatively simple scheme has been created to guide physicians on how to activate the PERT and which situations make this appropriate.

“A big part of the PERT value has been our ability to conduct a real-time virtual consultation where we leverage online technology to look at images together in order to agree on a strategy,” Dr. Channick explained.

Although frequently asked what specialists are needed for an effective PERT, Dr. Channick said it depends on institutional structures, the types of specialists available, and, in some cases, the specific characteristics of the patient. In many situations, a pulmonary vascular specialist and an interventional radiologist might be sufficient. In others, team members might include some combination of an interventional cardiologist, a cardiac surgeon, and a hematologist.

It is also appropriate to include clinicians likely to participate in care following acute treatment of the PE. “One of the most critical values to PERT is the ability to systematically follow patients” after the PE is treated, Dr. Channick said.

So far, there are no data to confirm patients managed with PERT achieve better outcomes than those who are not. Reductions in mortality, length of stay, and costs are reasonably anticipated and might eventually be demonstrated, but Dr. Channick said that PERTs already have value.

“I think the efficiency of care is important,”he said. He called PERT a “one-stop shopping” approach to ensuring that multiple strategies are considered systematically.

There are many anecdotal examples of the benefits of shared decision-making for PE treatment. In one, a pulmonary specialist in a PERT team narrowly averted a planned thrombolysis in a patient diagnosed with PE who was actually found to have severe pulmonary fibrosis, according to Dr. Channick.

Not least important, the shared decision-making of a PERT could relieve the burden of difficult choices in complex situations. Bad outcomes in PE can be unavoidable even with optimal therapy.

“To me personally, a very important benefit of being part of a PERT is the feeling that we are all in it together,” Dr. Channick said. “Patients can go from being pretty stable to being dead very quickly.”

The PERT Consortium has sponsored an annual meeting on PE since 2015. It also maintains an ongoing registry for PE data from member institutions. These data are expected to have increasing value for comparing the impact of patient characteristics, treatment strategies, and other variables on outcomes.

For clinicians who are uncertain whether the PE incidence at their institution justifies a PERT, Dr. Channick had some advice. “If you build it, they will clot,” he said, meaning that due to the frequency of PE, a PERT will generally have plenty of work once created.

SOURCE: VEITHSYMPOSIUM

NEW YORK – Seven years after the formation of the first pulmonary embolism response team (PERT), more than 100 institutions have joined the PERT Consortium, which was created to guide care and research for this thrombotic complication, according to a status report at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

“Why are PERTs needed? Pulmonary embolism patients are like snowflakes. No two are the same,” explained Richard Channick, MD, director of the pulmonary vascular disease program, University of California, Los Angeles.

Patient variability is an issue because algorithms for pulmonary embolism (PE) often differ at the point of diagnosis, such as the emergency department or intensive are unit, according to Dr. Channick, who was present when the first PERT was created in 2012 at Massachusetts General Hospital (MGH) in Boston. In addition, treatment algorithms can seem complex at a time when patients are deteriorating quickly.

“The treatment algorithms always say consider this or consider that, and then you get a recommendation with a 2B grade of evidence. So what do you do?” Dr. Channick asked, “This has really been crying for an organized approach.”

PERTs were created to fill this need. In most centers, PERTs are organized to respond to a diagnosis of PE wherever it occurs in the hospital. The goal is rapid activation of a team of experts who can reach a single consensus recommendation.

At MGH and UCLA, a similar relatively simple scheme has been created to guide physicians on how to activate the PERT and which situations make this appropriate.

“A big part of the PERT value has been our ability to conduct a real-time virtual consultation where we leverage online technology to look at images together in order to agree on a strategy,” Dr. Channick explained.

Although frequently asked what specialists are needed for an effective PERT, Dr. Channick said it depends on institutional structures, the types of specialists available, and, in some cases, the specific characteristics of the patient. In many situations, a pulmonary vascular specialist and an interventional radiologist might be sufficient. In others, team members might include some combination of an interventional cardiologist, a cardiac surgeon, and a hematologist.

It is also appropriate to include clinicians likely to participate in care following acute treatment of the PE. “One of the most critical values to PERT is the ability to systematically follow patients” after the PE is treated, Dr. Channick said.

So far, there are no data to confirm patients managed with PERT achieve better outcomes than those who are not. Reductions in mortality, length of stay, and costs are reasonably anticipated and might eventually be demonstrated, but Dr. Channick said that PERTs already have value.

“I think the efficiency of care is important,”he said. He called PERT a “one-stop shopping” approach to ensuring that multiple strategies are considered systematically.

There are many anecdotal examples of the benefits of shared decision-making for PE treatment. In one, a pulmonary specialist in a PERT team narrowly averted a planned thrombolysis in a patient diagnosed with PE who was actually found to have severe pulmonary fibrosis, according to Dr. Channick.

Not least important, the shared decision-making of a PERT could relieve the burden of difficult choices in complex situations. Bad outcomes in PE can be unavoidable even with optimal therapy.

“To me personally, a very important benefit of being part of a PERT is the feeling that we are all in it together,” Dr. Channick said. “Patients can go from being pretty stable to being dead very quickly.”

The PERT Consortium has sponsored an annual meeting on PE since 2015. It also maintains an ongoing registry for PE data from member institutions. These data are expected to have increasing value for comparing the impact of patient characteristics, treatment strategies, and other variables on outcomes.

For clinicians who are uncertain whether the PE incidence at their institution justifies a PERT, Dr. Channick had some advice. “If you build it, they will clot,” he said, meaning that due to the frequency of PE, a PERT will generally have plenty of work once created.

SOURCE: VEITHSYMPOSIUM

NEW YORK – Seven years after the formation of the first pulmonary embolism response team (PERT), more than 100 institutions have joined the PERT Consortium, which was created to guide care and research for this thrombotic complication, according to a status report at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

“Why are PERTs needed? Pulmonary embolism patients are like snowflakes. No two are the same,” explained Richard Channick, MD, director of the pulmonary vascular disease program, University of California, Los Angeles.

Patient variability is an issue because algorithms for pulmonary embolism (PE) often differ at the point of diagnosis, such as the emergency department or intensive are unit, according to Dr. Channick, who was present when the first PERT was created in 2012 at Massachusetts General Hospital (MGH) in Boston. In addition, treatment algorithms can seem complex at a time when patients are deteriorating quickly.

“The treatment algorithms always say consider this or consider that, and then you get a recommendation with a 2B grade of evidence. So what do you do?” Dr. Channick asked, “This has really been crying for an organized approach.”

PERTs were created to fill this need. In most centers, PERTs are organized to respond to a diagnosis of PE wherever it occurs in the hospital. The goal is rapid activation of a team of experts who can reach a single consensus recommendation.

At MGH and UCLA, a similar relatively simple scheme has been created to guide physicians on how to activate the PERT and which situations make this appropriate.

“A big part of the PERT value has been our ability to conduct a real-time virtual consultation where we leverage online technology to look at images together in order to agree on a strategy,” Dr. Channick explained.

Although frequently asked what specialists are needed for an effective PERT, Dr. Channick said it depends on institutional structures, the types of specialists available, and, in some cases, the specific characteristics of the patient. In many situations, a pulmonary vascular specialist and an interventional radiologist might be sufficient. In others, team members might include some combination of an interventional cardiologist, a cardiac surgeon, and a hematologist.

It is also appropriate to include clinicians likely to participate in care following acute treatment of the PE. “One of the most critical values to PERT is the ability to systematically follow patients” after the PE is treated, Dr. Channick said.

So far, there are no data to confirm patients managed with PERT achieve better outcomes than those who are not. Reductions in mortality, length of stay, and costs are reasonably anticipated and might eventually be demonstrated, but Dr. Channick said that PERTs already have value.

“I think the efficiency of care is important,”he said. He called PERT a “one-stop shopping” approach to ensuring that multiple strategies are considered systematically.

There are many anecdotal examples of the benefits of shared decision-making for PE treatment. In one, a pulmonary specialist in a PERT team narrowly averted a planned thrombolysis in a patient diagnosed with PE who was actually found to have severe pulmonary fibrosis, according to Dr. Channick.

Not least important, the shared decision-making of a PERT could relieve the burden of difficult choices in complex situations. Bad outcomes in PE can be unavoidable even with optimal therapy.

“To me personally, a very important benefit of being part of a PERT is the feeling that we are all in it together,” Dr. Channick said. “Patients can go from being pretty stable to being dead very quickly.”

The PERT Consortium has sponsored an annual meeting on PE since 2015. It also maintains an ongoing registry for PE data from member institutions. These data are expected to have increasing value for comparing the impact of patient characteristics, treatment strategies, and other variables on outcomes.

For clinicians who are uncertain whether the PE incidence at their institution justifies a PERT, Dr. Channick had some advice. “If you build it, they will clot,” he said, meaning that due to the frequency of PE, a PERT will generally have plenty of work once created.

SOURCE: VEITHSYMPOSIUM

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

The case

CDC/Jennifer Hulsey

A 67-year-old woman with a past medical history significant for diabetes mellitus type 2 and chronic kidney disease stage 3 was recently hospitalized for a community acquired pneumonia and treated for 5 days with moxifloxacin. In the week following this hospitalization, she began to have watery diarrhea and was found to have Clostridioides difficile diarrhea. She was treated with 10 days of oral vancomycin for her C. difficile infection (CDI). Approximately 3 weeks later, she again developed watery diarrhea with some abdominal cramping and has a leukocyte count of 22.4.

Key clinical questions

When is C. difficile considered recurrent?

C. difficile is considered recurrent when a patient experiences symptom onset and has a positive test in the 2-8 week period following the resolution of symptoms from the previous episode that had been confirmed with a positive test.¹

What is the recurrence rate for C. difficile?

Of patients who are initially diagnosed with C. difficile, about 20%-35% develop recurrence of their infection, and of those who experience recurrence, roughly 40%-60% will experience a second recurrence.²

What are the risk factors for recurrent C. difficile?

Risk factors for recurrence of C. difficile include older age (older than 65 years), female sex, Caucasian ethnicity, ongoing antibiotic use, concurrent proton pump inhibitor use, and more severe initial disease.

Also, receiving antineoplastic chemotherapy, being an organ transplant recipient, chronic kidney disease, inflammatory bowel disease, hypogammaglobulinemia, or other immunodeficiency, as well as having exposure to infected adult or infant carrier of C. difficile have all been risk factors for recurrent disease. There is still some degree of ongoing controversy over the role of proton pump inhibitors as a risk factor.²

What are the treatment options for initial C. difficile infection?

The recent Infectious Diseases Society of America (IDSA) guidelines recommend treating for an initial CDI with a 10-day course of oral vancomycin or fidaxomicin instead of metronidazole. This change is based on a combined analysis of two large randomized controlled trials that demonstrated better clinical response rates with vancomycin, compared with metronidazole (81.1% vs. 72.7%; P = .002).^1,3

What are the treatment options for first recurrence?

The data is overall limited in treatment of first recurrence of CDI. The IDSA guidelines recommend that a first recurrence of CDI may be treated with oral vancomycin followed by a tapered and pulsed regimen or with a 10-day course of fidaxomicin. If metronidazole was used for the first episode, a 10-day course of vancomycin can be used.¹

What are the treatment options for second and subsequent recurrences?

Second or subsequent CDI recurrences may be treated with oral vancomycin as a tapered and pulsed-dose regimen or with fidaxomicin as described above, but this is based on low quality of evidence.

The IDSA guidelines strongly recommend fecal microbiota transplantation (FMT) for patients who have two or more C. difficile recurrences and in whom standard antibiotic treatment has not been successful. FMT has demonstrated high efficacy rates of 80%-90% for clinical remission of recurrent CDI.

FMT can be administered through various routes. The choice of delivery depends in part on local expertise, patient preference, cost, and risk of the procedure.^1,4,5,6

What new therapies exist for reducing recurrence?

Bezlotoxumab is a humanized monoclonal antibody directed against C. difficile toxin B that was approved by the Food and Drug Administration in 2016 for prevention of recurrent CDI. Randomized placebo-controlled trials demonstrated that a single infusion of bezlotoxumab, given in combination with usual antibiotics for CDI in adults, was effective in reducing CDI recurrence within 12 weeks (rate of recurrent infection in both trials was 16.5% in the bezlotoxumab groups and 26.6% in the placebo groups).

In a post hoc analysis, the highest benefit was in patients with three or more risk factors: older than 65 years, history of CDI, immunocompromised status, or severe CDI. Although the best strategy for prevention of CDI recurrence remains to be determined, bezlotoxumab remains an option.^7,8

Back to the case

The patient had a C. difficile polymerase chain reaction test sent that came back positive for C. difficile. Because she had previously been treated with a 10-day course of oral vancomycin, she was started on a tapered and pulsed-dose regimen of oral vancomycin. Five days later her diarrhea resolved, and her leukocyte count returned to normal.

Dr. Bell is associate clinical professor in the division of hospital medicine at the University of California, San Diego, Medical Center. Dr. Farkhondehpour is a hospitalist and assistant clinical professor at UC San Diego Health.

References

1. McDonald L et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994.

2. Hopkins R and Wilson R. Treatment of recurrent Clostridium difficile colitis: A narrative review. Gastroenterol Rep (Oxf). 2018 Feb;6(1):21-8.

3. Johnson S et al. (2014). Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54.

4. van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.

5. Cammarota G et al. Randomised clinical trial: Faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43.

6. Kelly C et al. Effect of fecal microbiota transplantation on recurrence in multiple recurrent Clostridium difficile infection. Ann Intern Med. 2016 Nov 1;165(9):609-16.

7. Gerding DN et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-56.

8. Wilcox M et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017 Jan 26;376(4):305-17.

PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.

Mitchel L. Zoler/MDedge News

“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.

While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.

In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A^1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A_1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.

“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A_1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.

If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.

“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.

The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.

The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.

DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.

[email protected]

SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.

PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.

Mitchel L. Zoler/MDedge News

“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.

While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.

In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A^1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A_1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.

“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A_1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.

If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.

“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.

The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.

The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.

DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.

[email protected]

SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.

PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.

Mitchel L. Zoler/MDedge News

“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.

While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.

In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A^1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A_1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.

“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A_1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.

If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.

“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.

The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.

The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.

DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.

[email protected]

SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.

The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.

The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.

The approval is for patients who have limited or no alternative treatment options and includes a label warning regarding cefiderocol’s higher all-cause mortality observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).

The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.

Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.

“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.

Fetroja is a product of Shionogi.

[email protected]

The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.

The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.

The approval is for patients who have limited or no alternative treatment options and includes a label warning regarding cefiderocol’s higher all-cause mortality observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).

The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.

Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.

“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.

Fetroja is a product of Shionogi.

[email protected]

The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.

The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.

The approval is for patients who have limited or no alternative treatment options and includes a label warning regarding cefiderocol’s higher all-cause mortality observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).

The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.

Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.

“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.

Fetroja is a product of Shionogi.

[email protected]

PHM19 session

Mitigating the harm we cause learners in medical education

Presenters

Benjamin Kinnear, MD, MEd

Andrew Olson, MD

Matthew Kelleher, MD, MEd

Session summary

Dr. Kinnear, Dr. Olson, and Dr. Kelleher expertly led this TED-Talk style session at Pediatric Hospital Medicine 2019, convincing the audience that medical educators persistently harm the learners under their supervision.

Dr. Kinnear, of Cincinnati Children’s Hospital, opened the session noting that the path through medical school presently has a perverse focus on grades as a necessary achievement. As an expert in competency-based assessment, he asserted that the current learner assessment strategy is neither valid nor robust enough to indicate actual competence. Summary assessments presented throughout medical school are lacking continuous constructive feedback, leaving early residents in a state of shock when receiving corrective or negative assessments. He also noted that structurally many rotations create both team and patient discontinuity, leaving the learner with a feeling of detachment and limited ownership of the human patient under his/her/their care.

Dr. Olson of the University of Minnesota next described the need for the USMLE STEP 1 exam to be transitioned to a pass/fail endeavor. He cited the error of measurement of 24 points (i.e., the same test taker could have a 220 one day and a 244 the next) and the potential loss of valuable rotation experiences during the several-month period of intense study. He challenged audience members to complete an esoteric exam question to prove his point and asserted that many learners are lacking in humility, communication skills, and professionalism, and seek only the honors designation on rotations. He likened the experience of medical students on rotation and residents on service weeks to a series of first dates and affirmed the value of longitudinal learner-educator relationships.

Further, he outlined the detachment of learners from patient outcomes, demonstrated by frequent hand-offs and rotation transitions. Dr Olson also cited medical pedagogy as failing to meet the known needs of adult learners to engage in deliberate progressive practice, reflective practice, or to use concepts such as spacing or interleaving to reinforce knowledge.

Dr. Kelleher, also of Cincinnati Children’s Hospital, ended the session by taking those in attendance on an imagined “what-if” journey where each of the wrongs currently done to early learners in medical education were corrected. This included engagement in daily reflection (5 minutes at a time), reporting system issues on rounds that had failed the patient, presenting learners with a CV of attending failures to reinforce the imperfection that is a reality in medicine, praising learners when they admit “they don’t know the answer” to a question posed on rounds, completing assessments in real time in the learner’s presence, rounding until specific feedback can be identified for each learner on the team, having a kiosk on each floor where ANY team member could provide feedback to learners, using cognitive science on rounds for teaching (i.e., Socratic) rather than pimping, modeling interprofessional teamwork daily using a culture of vulnerability rather than infallibility (i.e., airline culture), and by encouraging the attending to care for patients or complete tasks independently, showing the value of education over service and model ideal family-centered communication with the team.

One might wonder, if all of the above were accomplished at the request of our talented presenters, would a pass/fail USMLE world where medical education was learner centered and filled with longitudinal relationships with teams and patients, and outcomes were connected to education produce more engaged, knowledgeable, and holistic physicians? According to this team of presenters, yes.
 

Key takeaways

• Current processes in medical education are harming today’s adult learner.

• Harms include reliance on numerical rather than competency-based assessment, fragmented learning environments, focus on perfection rather than improvement, ignorance of updates in cognitive science for instructional methodology, and individualist rather than team-based learning.

• Reforms are needed to remedy harms in health professional education, including making USMLE pass/fail, creating a learning-centered rather than service-centered residency environment, encouraging longitudinal relationships between teacher and learner, and connecting education to clinical outcomes.

Dr. King is associate program director, University of Minnesota Pediatric Residency Program, Minneapolis.

PHM19 session

Mitigating the harm we cause learners in medical education

Presenters

Benjamin Kinnear, MD, MEd

Andrew Olson, MD

Matthew Kelleher, MD, MEd

Session summary

Dr. Kinnear, Dr. Olson, and Dr. Kelleher expertly led this TED-Talk style session at Pediatric Hospital Medicine 2019, convincing the audience that medical educators persistently harm the learners under their supervision.

Dr. Kinnear, of Cincinnati Children’s Hospital, opened the session noting that the path through medical school presently has a perverse focus on grades as a necessary achievement. As an expert in competency-based assessment, he asserted that the current learner assessment strategy is neither valid nor robust enough to indicate actual competence. Summary assessments presented throughout medical school are lacking continuous constructive feedback, leaving early residents in a state of shock when receiving corrective or negative assessments. He also noted that structurally many rotations create both team and patient discontinuity, leaving the learner with a feeling of detachment and limited ownership of the human patient under his/her/their care.

Dr. Olson of the University of Minnesota next described the need for the USMLE STEP 1 exam to be transitioned to a pass/fail endeavor. He cited the error of measurement of 24 points (i.e., the same test taker could have a 220 one day and a 244 the next) and the potential loss of valuable rotation experiences during the several-month period of intense study. He challenged audience members to complete an esoteric exam question to prove his point and asserted that many learners are lacking in humility, communication skills, and professionalism, and seek only the honors designation on rotations. He likened the experience of medical students on rotation and residents on service weeks to a series of first dates and affirmed the value of longitudinal learner-educator relationships.

Further, he outlined the detachment of learners from patient outcomes, demonstrated by frequent hand-offs and rotation transitions. Dr Olson also cited medical pedagogy as failing to meet the known needs of adult learners to engage in deliberate progressive practice, reflective practice, or to use concepts such as spacing or interleaving to reinforce knowledge.

Dr. Kelleher, also of Cincinnati Children’s Hospital, ended the session by taking those in attendance on an imagined “what-if” journey where each of the wrongs currently done to early learners in medical education were corrected. This included engagement in daily reflection (5 minutes at a time), reporting system issues on rounds that had failed the patient, presenting learners with a CV of attending failures to reinforce the imperfection that is a reality in medicine, praising learners when they admit “they don’t know the answer” to a question posed on rounds, completing assessments in real time in the learner’s presence, rounding until specific feedback can be identified for each learner on the team, having a kiosk on each floor where ANY team member could provide feedback to learners, using cognitive science on rounds for teaching (i.e., Socratic) rather than pimping, modeling interprofessional teamwork daily using a culture of vulnerability rather than infallibility (i.e., airline culture), and by encouraging the attending to care for patients or complete tasks independently, showing the value of education over service and model ideal family-centered communication with the team.

One might wonder, if all of the above were accomplished at the request of our talented presenters, would a pass/fail USMLE world where medical education was learner centered and filled with longitudinal relationships with teams and patients, and outcomes were connected to education produce more engaged, knowledgeable, and holistic physicians? According to this team of presenters, yes.
 

Key takeaways

• Current processes in medical education are harming today’s adult learner.

• Harms include reliance on numerical rather than competency-based assessment, fragmented learning environments, focus on perfection rather than improvement, ignorance of updates in cognitive science for instructional methodology, and individualist rather than team-based learning.

• Reforms are needed to remedy harms in health professional education, including making USMLE pass/fail, creating a learning-centered rather than service-centered residency environment, encouraging longitudinal relationships between teacher and learner, and connecting education to clinical outcomes.

Dr. King is associate program director, University of Minnesota Pediatric Residency Program, Minneapolis.

PHM19 session

Mitigating the harm we cause learners in medical education

Presenters

Benjamin Kinnear, MD, MEd

Andrew Olson, MD

Matthew Kelleher, MD, MEd

Session summary

Dr. Kinnear, Dr. Olson, and Dr. Kelleher expertly led this TED-Talk style session at Pediatric Hospital Medicine 2019, convincing the audience that medical educators persistently harm the learners under their supervision.

Dr. Kinnear, of Cincinnati Children’s Hospital, opened the session noting that the path through medical school presently has a perverse focus on grades as a necessary achievement. As an expert in competency-based assessment, he asserted that the current learner assessment strategy is neither valid nor robust enough to indicate actual competence. Summary assessments presented throughout medical school are lacking continuous constructive feedback, leaving early residents in a state of shock when receiving corrective or negative assessments. He also noted that structurally many rotations create both team and patient discontinuity, leaving the learner with a feeling of detachment and limited ownership of the human patient under his/her/their care.

Dr. Olson of the University of Minnesota next described the need for the USMLE STEP 1 exam to be transitioned to a pass/fail endeavor. He cited the error of measurement of 24 points (i.e., the same test taker could have a 220 one day and a 244 the next) and the potential loss of valuable rotation experiences during the several-month period of intense study. He challenged audience members to complete an esoteric exam question to prove his point and asserted that many learners are lacking in humility, communication skills, and professionalism, and seek only the honors designation on rotations. He likened the experience of medical students on rotation and residents on service weeks to a series of first dates and affirmed the value of longitudinal learner-educator relationships.

Further, he outlined the detachment of learners from patient outcomes, demonstrated by frequent hand-offs and rotation transitions. Dr Olson also cited medical pedagogy as failing to meet the known needs of adult learners to engage in deliberate progressive practice, reflective practice, or to use concepts such as spacing or interleaving to reinforce knowledge.

Dr. Kelleher, also of Cincinnati Children’s Hospital, ended the session by taking those in attendance on an imagined “what-if” journey where each of the wrongs currently done to early learners in medical education were corrected. This included engagement in daily reflection (5 minutes at a time), reporting system issues on rounds that had failed the patient, presenting learners with a CV of attending failures to reinforce the imperfection that is a reality in medicine, praising learners when they admit “they don’t know the answer” to a question posed on rounds, completing assessments in real time in the learner’s presence, rounding until specific feedback can be identified for each learner on the team, having a kiosk on each floor where ANY team member could provide feedback to learners, using cognitive science on rounds for teaching (i.e., Socratic) rather than pimping, modeling interprofessional teamwork daily using a culture of vulnerability rather than infallibility (i.e., airline culture), and by encouraging the attending to care for patients or complete tasks independently, showing the value of education over service and model ideal family-centered communication with the team.

One might wonder, if all of the above were accomplished at the request of our talented presenters, would a pass/fail USMLE world where medical education was learner centered and filled with longitudinal relationships with teams and patients, and outcomes were connected to education produce more engaged, knowledgeable, and holistic physicians? According to this team of presenters, yes.
 

Key takeaways

• Current processes in medical education are harming today’s adult learner.

• Harms include reliance on numerical rather than competency-based assessment, fragmented learning environments, focus on perfection rather than improvement, ignorance of updates in cognitive science for instructional methodology, and individualist rather than team-based learning.

• Reforms are needed to remedy harms in health professional education, including making USMLE pass/fail, creating a learning-centered rather than service-centered residency environment, encouraging longitudinal relationships between teacher and learner, and connecting education to clinical outcomes.

Dr. King is associate program director, University of Minnesota Pediatric Residency Program, Minneapolis.

The Centers for Disease Control and Prevention has updated information about cases of e-cigarette, or vaping, product use–associated lung injury (EVALI): As of Nov. 12, there have been 2,172 cases reported from 49 states (all except Alaska), the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands). Forty-two deaths have been confirmed in 24 states and the District of Columbia, the CDC reported.

ArminStautBerlin/Thinkstock

Laboratory test results of bronchoalveolar lavage fluid samples from 29 patients submitted to CDC from 10 states found vitamin E acetate in all of the samples. This is the first time a chemical of concern has been found in biologic samples from patients with EVALI. These findings provide direct evidence of vitamin E acetate at the primary site of injury within the lungs.

Tetrahydrocannabinol (THC) was identified in 82% of the samples and nicotine was identified in 62% of the samples. Testing continues for other chemicals including plant oils, petroleum distillates like mineral oil, medium-chain triglycerides oil, and terpenes, which are compounds commonly found in or added to THC products. None of these chemicals has been detected in the bronchoalveolar lavage fluid samples tested.

For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.

[email protected]

The Centers for Disease Control and Prevention has updated information about cases of e-cigarette, or vaping, product use–associated lung injury (EVALI): As of Nov. 12, there have been 2,172 cases reported from 49 states (all except Alaska), the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands). Forty-two deaths have been confirmed in 24 states and the District of Columbia, the CDC reported.

ArminStautBerlin/Thinkstock

Laboratory test results of bronchoalveolar lavage fluid samples from 29 patients submitted to CDC from 10 states found vitamin E acetate in all of the samples. This is the first time a chemical of concern has been found in biologic samples from patients with EVALI. These findings provide direct evidence of vitamin E acetate at the primary site of injury within the lungs.

Tetrahydrocannabinol (THC) was identified in 82% of the samples and nicotine was identified in 62% of the samples. Testing continues for other chemicals including plant oils, petroleum distillates like mineral oil, medium-chain triglycerides oil, and terpenes, which are compounds commonly found in or added to THC products. None of these chemicals has been detected in the bronchoalveolar lavage fluid samples tested.

For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.

[email protected]

The Centers for Disease Control and Prevention has updated information about cases of e-cigarette, or vaping, product use–associated lung injury (EVALI): As of Nov. 12, there have been 2,172 cases reported from 49 states (all except Alaska), the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands). Forty-two deaths have been confirmed in 24 states and the District of Columbia, the CDC reported.

ArminStautBerlin/Thinkstock

Laboratory test results of bronchoalveolar lavage fluid samples from 29 patients submitted to CDC from 10 states found vitamin E acetate in all of the samples. This is the first time a chemical of concern has been found in biologic samples from patients with EVALI. These findings provide direct evidence of vitamin E acetate at the primary site of injury within the lungs.

Tetrahydrocannabinol (THC) was identified in 82% of the samples and nicotine was identified in 62% of the samples. Testing continues for other chemicals including plant oils, petroleum distillates like mineral oil, medium-chain triglycerides oil, and terpenes, which are compounds commonly found in or added to THC products. None of these chemicals has been detected in the bronchoalveolar lavage fluid samples tested.

For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.

[email protected]

SAN ANTONIO – Although there has been a general decline in transfusion-related anaphylaxis and acute infections over time among hospitalized older adults in the United States, incidence rates for both transfusion-related acute lung injury and transfusion-associated circulatory overload have risen over the last decade, according to researchers from the Food and Drug Administration.

Mikhail Menis, PharmD, an epidemiologist at the FDA Center for Biologics Evaluation and Research (CBER) and colleagues queried large Medicare databases to assess trends in transfusion-related adverse events among adults aged 65 years and older.

The investigators saw “substantially higher risk of all outcomes among immunocompromised beneficiaries, which could be related to higher blood use of all blood components, especially platelets, underlying conditions such as malignancies, and treatments such as chemotherapy or radiation, which need further investigation,” Dr. Menis said at the annual meeting of AABB, the group formerly known as the American Association of Blood Banks.

He reported data from a series of studies on four categories of transfusion-related events that may be life-threatening or fatal: transfusion-related anaphylaxis (TRA), transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and acute infection following transfusion (AIFT).

For each type of event, the researchers looked at overall incidence and the incidence by immune status, calendar year, blood components transfused, number of units transfused, age, sex, and race.
 

Anaphylaxis (TRA)

TRA may be caused by preformed immunoglobin E (IgE) antibodies to proteins in the plasma in transfused blood products or by preformed IgA antibodies in patients who are likely IgA deficient, Dr. Menis said.

The overall incidence of TRA among 8,833,817 inpatient transfusions stays for elderly beneficiaries from 2012 through 2018 was 7.1 per 100,000 stays. The rate was higher for immunocompromised patients, at 9.6, than it was among nonimmunocompromised patients, at 6.5.

The rates varied by every subgroup measured except immune status. Annual rates showed a downward trend, from 8.7 per 100,000 in 2012, to 5.1 in 2017 and 6.4 in 2018. The decline in occurrence may be caused by a decline in inpatient blood utilization during the study period, particularly among immunocompromised patients.

TRA rates increased with five or more units transfused. The risk was significantly reduced in the oldest group of patients versus the youngest (P less than .001), which supports the immune-based mechanism of action of anaphylaxis, Dr. Menis said.

They also found that TRA rates were substantially higher among patients who had received platelet and/or plasma transfusions, compared with patients who received only red blood cells (RBCs).

Additionally, risk for TRA was significantly higher among men than it was among women (9.3 vs. 5.4) and among white versus nonwhite patients (7.8 vs. 3.8).

The evidence suggested TRA cases are likely to be severe in this population, with inpatient mortality of 7.1%, and hospital stays of 7 days or longer in about 58% of cases, indicating the importance of TRA prevention, Dr. Menis said.

The investigators plan to perform multivariate regression analyses to assess potential risk factors, including underlying comorbidities and health histories for TRA occurrence for both the overall population and by immune status.
 

Acute lung injury (TRALI)

TRALI is a rare but serious adverse event, a clinical syndrome with onset within 6 hours of transfusion that presents as acute hypoxemia, respiratory distress, and noncardiogenic pulmonary edema.

Among 17,771,193 total inpatient transfusion stays, the overall incidence of TRALI was 33.2 per 100,000. The rate was 55.9 for immunocompromised patients versus 28.4 for nonimmunocompromised patients. The rate ratio was 2.0 (P less than .001).

The difference by immune status may be caused by higher blood utilizations with more units transfused per stay among immunocompromised patients, a higher incidence of prior transfusions among these patients, higher use of irradiated blood components that may lead to accumulation of proinflammatory mediators in blood products during storage, or underlying comorbidities.

The overall rate increased from 14.3 in 2007 to 56.4 in 2018. The rates increased proportionally among both immunocompromised and nonimmunocompromised patients.

As with TRA, the incidence of TRALI was higher in patients with five or more units transfused, while the incidence declined with age, likely caused by declining blood use and age-related changes in neutrophil function, Dr. Menis said.

TRALI rates were slightly higher among men than among women, as well as higher among white patients than among nonwhite patients.

Overall, TRALI rates were higher for patients who received platelets either alone or in combination with RBCs and/or plasma. The highest rates were among patients who received RBCs, plasma and platelets.

Dr. Menis called for studies to determine what effects the processing and storage of blood components may have on TRALI occurrence; he and his colleagues also are planning regression analyses to assess potential risk factors for this complication.
 

Circulatory overload (TACO)

TACO is one of the leading reported causes of transfusion-related fatalities in the U.S., with onset usually occurring within 6 hours of transfusion, presenting as acute respiratory distress with dyspnea, orthopnea, increased blood pressure, and cardiogenic pulmonary edema.

The overall incidence of TACO among hospitalized patients aged 65 years and older from 2011 through 2018 was 86.3 per 100,000 stays. The incidences were 128.3 in immunocompromised and 76.0 in nonimmunocompromised patients. The rate ratio for TACO in immunocompromised versus nonimmunocompromised patients was 1.70 (P less than .001).

Overall incidence rates of TACO rose from 62 per 100,000 stays in 2011 to 119.8 in 2018. As with other adverse events, incident rates rose with the number of units transfused.

Rates of TACO were significantly higher among women than they were among men (94.6 vs. 75.9 per 100,000; P less than .001), which could be caused by the higher mean age of women and/or a lower tolerance for increased blood volume from transfusion.

The study results also suggested that TACO and TRALI may coexist, based on evidence that 3.5% of all TACO stays also had diagnostic codes for TRALI. The frequency of co-occurrence of these two adverse events also increased over time, which may be caused by improved awareness, Dr. Menis said.
 

Infections (AIFT)

Acute infections following transfusion can lead to prolonged hospitalizations, sepsis, septic shock, and death. Those most at risk include elderly and immunocompromised patients because of high utilization of blood products, comorbidities, and decreased immune function.

Among 8,833,817 stays, the overall rate per 100,000 stays was 2.1. The rate for immunocompromised patients was 5.4, compared with 1.2 for nonimmunocompromised patients, for a rate ratio of 4.4 (P less than .001).

The incidence rate declined significantly (P = .03) over the study period, with the 3 latest years having the lowest rates.

Rates increased substantially among immunocompromised patients by the number of units transfused, but remained relatively stable among nonimmunocompromised patients.

Infection rates declined with age, from 2.7 per 100,000 stays for patients aged 65-68 years to 1.2 per 100,000 for those aged 85 years and older.

As with other adverse events, AIFT rates were likely related to the blood components transfused, with substantially higher rates for stays during which platelets were transfused either alone or with RBCs, compared with RBCs alone. This could be caused by the room-temperature storage of platelets and higher number of platelets units transfused, compared with RBCs alone, especially among immunocompromised patients.

In all, 51.9% of AIFT cases also had sepsis noted in the medical record, indicating high severity and emphasizing the importance of AIFT prevention, Dr. Menis said.

The studies were funded by the FDA, and Dr. Menis is an FDA employee. He reported having no conflicts of interest.

SAN ANTONIO – Although there has been a general decline in transfusion-related anaphylaxis and acute infections over time among hospitalized older adults in the United States, incidence rates for both transfusion-related acute lung injury and transfusion-associated circulatory overload have risen over the last decade, according to researchers from the Food and Drug Administration.

Mikhail Menis, PharmD, an epidemiologist at the FDA Center for Biologics Evaluation and Research (CBER) and colleagues queried large Medicare databases to assess trends in transfusion-related adverse events among adults aged 65 years and older.

The investigators saw “substantially higher risk of all outcomes among immunocompromised beneficiaries, which could be related to higher blood use of all blood components, especially platelets, underlying conditions such as malignancies, and treatments such as chemotherapy or radiation, which need further investigation,” Dr. Menis said at the annual meeting of AABB, the group formerly known as the American Association of Blood Banks.

He reported data from a series of studies on four categories of transfusion-related events that may be life-threatening or fatal: transfusion-related anaphylaxis (TRA), transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and acute infection following transfusion (AIFT).

For each type of event, the researchers looked at overall incidence and the incidence by immune status, calendar year, blood components transfused, number of units transfused, age, sex, and race.
 

Anaphylaxis (TRA)

TRA may be caused by preformed immunoglobin E (IgE) antibodies to proteins in the plasma in transfused blood products or by preformed IgA antibodies in patients who are likely IgA deficient, Dr. Menis said.

The overall incidence of TRA among 8,833,817 inpatient transfusions stays for elderly beneficiaries from 2012 through 2018 was 7.1 per 100,000 stays. The rate was higher for immunocompromised patients, at 9.6, than it was among nonimmunocompromised patients, at 6.5.

The rates varied by every subgroup measured except immune status. Annual rates showed a downward trend, from 8.7 per 100,000 in 2012, to 5.1 in 2017 and 6.4 in 2018. The decline in occurrence may be caused by a decline in inpatient blood utilization during the study period, particularly among immunocompromised patients.

TRA rates increased with five or more units transfused. The risk was significantly reduced in the oldest group of patients versus the youngest (P less than .001), which supports the immune-based mechanism of action of anaphylaxis, Dr. Menis said.

They also found that TRA rates were substantially higher among patients who had received platelet and/or plasma transfusions, compared with patients who received only red blood cells (RBCs).

Additionally, risk for TRA was significantly higher among men than it was among women (9.3 vs. 5.4) and among white versus nonwhite patients (7.8 vs. 3.8).

The evidence suggested TRA cases are likely to be severe in this population, with inpatient mortality of 7.1%, and hospital stays of 7 days or longer in about 58% of cases, indicating the importance of TRA prevention, Dr. Menis said.

The investigators plan to perform multivariate regression analyses to assess potential risk factors, including underlying comorbidities and health histories for TRA occurrence for both the overall population and by immune status.
 

Acute lung injury (TRALI)

TRALI is a rare but serious adverse event, a clinical syndrome with onset within 6 hours of transfusion that presents as acute hypoxemia, respiratory distress, and noncardiogenic pulmonary edema.

Among 17,771,193 total inpatient transfusion stays, the overall incidence of TRALI was 33.2 per 100,000. The rate was 55.9 for immunocompromised patients versus 28.4 for nonimmunocompromised patients. The rate ratio was 2.0 (P less than .001).

The difference by immune status may be caused by higher blood utilizations with more units transfused per stay among immunocompromised patients, a higher incidence of prior transfusions among these patients, higher use of irradiated blood components that may lead to accumulation of proinflammatory mediators in blood products during storage, or underlying comorbidities.

The overall rate increased from 14.3 in 2007 to 56.4 in 2018. The rates increased proportionally among both immunocompromised and nonimmunocompromised patients.

As with TRA, the incidence of TRALI was higher in patients with five or more units transfused, while the incidence declined with age, likely caused by declining blood use and age-related changes in neutrophil function, Dr. Menis said.

TRALI rates were slightly higher among men than among women, as well as higher among white patients than among nonwhite patients.

Overall, TRALI rates were higher for patients who received platelets either alone or in combination with RBCs and/or plasma. The highest rates were among patients who received RBCs, plasma and platelets.

Dr. Menis called for studies to determine what effects the processing and storage of blood components may have on TRALI occurrence; he and his colleagues also are planning regression analyses to assess potential risk factors for this complication.
 

Circulatory overload (TACO)

TACO is one of the leading reported causes of transfusion-related fatalities in the U.S., with onset usually occurring within 6 hours of transfusion, presenting as acute respiratory distress with dyspnea, orthopnea, increased blood pressure, and cardiogenic pulmonary edema.

The overall incidence of TACO among hospitalized patients aged 65 years and older from 2011 through 2018 was 86.3 per 100,000 stays. The incidences were 128.3 in immunocompromised and 76.0 in nonimmunocompromised patients. The rate ratio for TACO in immunocompromised versus nonimmunocompromised patients was 1.70 (P less than .001).

Overall incidence rates of TACO rose from 62 per 100,000 stays in 2011 to 119.8 in 2018. As with other adverse events, incident rates rose with the number of units transfused.

Rates of TACO were significantly higher among women than they were among men (94.6 vs. 75.9 per 100,000; P less than .001), which could be caused by the higher mean age of women and/or a lower tolerance for increased blood volume from transfusion.

The study results also suggested that TACO and TRALI may coexist, based on evidence that 3.5% of all TACO stays also had diagnostic codes for TRALI. The frequency of co-occurrence of these two adverse events also increased over time, which may be caused by improved awareness, Dr. Menis said.
 

Infections (AIFT)

Acute infections following transfusion can lead to prolonged hospitalizations, sepsis, septic shock, and death. Those most at risk include elderly and immunocompromised patients because of high utilization of blood products, comorbidities, and decreased immune function.

Among 8,833,817 stays, the overall rate per 100,000 stays was 2.1. The rate for immunocompromised patients was 5.4, compared with 1.2 for nonimmunocompromised patients, for a rate ratio of 4.4 (P less than .001).

The incidence rate declined significantly (P = .03) over the study period, with the 3 latest years having the lowest rates.

Rates increased substantially among immunocompromised patients by the number of units transfused, but remained relatively stable among nonimmunocompromised patients.

Infection rates declined with age, from 2.7 per 100,000 stays for patients aged 65-68 years to 1.2 per 100,000 for those aged 85 years and older.

As with other adverse events, AIFT rates were likely related to the blood components transfused, with substantially higher rates for stays during which platelets were transfused either alone or with RBCs, compared with RBCs alone. This could be caused by the room-temperature storage of platelets and higher number of platelets units transfused, compared with RBCs alone, especially among immunocompromised patients.

In all, 51.9% of AIFT cases also had sepsis noted in the medical record, indicating high severity and emphasizing the importance of AIFT prevention, Dr. Menis said.

The studies were funded by the FDA, and Dr. Menis is an FDA employee. He reported having no conflicts of interest.

SAN ANTONIO – Although there has been a general decline in transfusion-related anaphylaxis and acute infections over time among hospitalized older adults in the United States, incidence rates for both transfusion-related acute lung injury and transfusion-associated circulatory overload have risen over the last decade, according to researchers from the Food and Drug Administration.

Mikhail Menis, PharmD, an epidemiologist at the FDA Center for Biologics Evaluation and Research (CBER) and colleagues queried large Medicare databases to assess trends in transfusion-related adverse events among adults aged 65 years and older.

The investigators saw “substantially higher risk of all outcomes among immunocompromised beneficiaries, which could be related to higher blood use of all blood components, especially platelets, underlying conditions such as malignancies, and treatments such as chemotherapy or radiation, which need further investigation,” Dr. Menis said at the annual meeting of AABB, the group formerly known as the American Association of Blood Banks.

He reported data from a series of studies on four categories of transfusion-related events that may be life-threatening or fatal: transfusion-related anaphylaxis (TRA), transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and acute infection following transfusion (AIFT).

For each type of event, the researchers looked at overall incidence and the incidence by immune status, calendar year, blood components transfused, number of units transfused, age, sex, and race.
 

Anaphylaxis (TRA)

TRA may be caused by preformed immunoglobin E (IgE) antibodies to proteins in the plasma in transfused blood products or by preformed IgA antibodies in patients who are likely IgA deficient, Dr. Menis said.

The overall incidence of TRA among 8,833,817 inpatient transfusions stays for elderly beneficiaries from 2012 through 2018 was 7.1 per 100,000 stays. The rate was higher for immunocompromised patients, at 9.6, than it was among nonimmunocompromised patients, at 6.5.

The rates varied by every subgroup measured except immune status. Annual rates showed a downward trend, from 8.7 per 100,000 in 2012, to 5.1 in 2017 and 6.4 in 2018. The decline in occurrence may be caused by a decline in inpatient blood utilization during the study period, particularly among immunocompromised patients.

TRA rates increased with five or more units transfused. The risk was significantly reduced in the oldest group of patients versus the youngest (P less than .001), which supports the immune-based mechanism of action of anaphylaxis, Dr. Menis said.

They also found that TRA rates were substantially higher among patients who had received platelet and/or plasma transfusions, compared with patients who received only red blood cells (RBCs).

Additionally, risk for TRA was significantly higher among men than it was among women (9.3 vs. 5.4) and among white versus nonwhite patients (7.8 vs. 3.8).

The evidence suggested TRA cases are likely to be severe in this population, with inpatient mortality of 7.1%, and hospital stays of 7 days or longer in about 58% of cases, indicating the importance of TRA prevention, Dr. Menis said.

The investigators plan to perform multivariate regression analyses to assess potential risk factors, including underlying comorbidities and health histories for TRA occurrence for both the overall population and by immune status.
 

Acute lung injury (TRALI)

TRALI is a rare but serious adverse event, a clinical syndrome with onset within 6 hours of transfusion that presents as acute hypoxemia, respiratory distress, and noncardiogenic pulmonary edema.

Among 17,771,193 total inpatient transfusion stays, the overall incidence of TRALI was 33.2 per 100,000. The rate was 55.9 for immunocompromised patients versus 28.4 for nonimmunocompromised patients. The rate ratio was 2.0 (P less than .001).

The difference by immune status may be caused by higher blood utilizations with more units transfused per stay among immunocompromised patients, a higher incidence of prior transfusions among these patients, higher use of irradiated blood components that may lead to accumulation of proinflammatory mediators in blood products during storage, or underlying comorbidities.

The overall rate increased from 14.3 in 2007 to 56.4 in 2018. The rates increased proportionally among both immunocompromised and nonimmunocompromised patients.

As with TRA, the incidence of TRALI was higher in patients with five or more units transfused, while the incidence declined with age, likely caused by declining blood use and age-related changes in neutrophil function, Dr. Menis said.

TRALI rates were slightly higher among men than among women, as well as higher among white patients than among nonwhite patients.

Overall, TRALI rates were higher for patients who received platelets either alone or in combination with RBCs and/or plasma. The highest rates were among patients who received RBCs, plasma and platelets.

Dr. Menis called for studies to determine what effects the processing and storage of blood components may have on TRALI occurrence; he and his colleagues also are planning regression analyses to assess potential risk factors for this complication.
 

Circulatory overload (TACO)

TACO is one of the leading reported causes of transfusion-related fatalities in the U.S., with onset usually occurring within 6 hours of transfusion, presenting as acute respiratory distress with dyspnea, orthopnea, increased blood pressure, and cardiogenic pulmonary edema.

The overall incidence of TACO among hospitalized patients aged 65 years and older from 2011 through 2018 was 86.3 per 100,000 stays. The incidences were 128.3 in immunocompromised and 76.0 in nonimmunocompromised patients. The rate ratio for TACO in immunocompromised versus nonimmunocompromised patients was 1.70 (P less than .001).

Overall incidence rates of TACO rose from 62 per 100,000 stays in 2011 to 119.8 in 2018. As with other adverse events, incident rates rose with the number of units transfused.

Rates of TACO were significantly higher among women than they were among men (94.6 vs. 75.9 per 100,000; P less than .001), which could be caused by the higher mean age of women and/or a lower tolerance for increased blood volume from transfusion.

The study results also suggested that TACO and TRALI may coexist, based on evidence that 3.5% of all TACO stays also had diagnostic codes for TRALI. The frequency of co-occurrence of these two adverse events also increased over time, which may be caused by improved awareness, Dr. Menis said.
 

Infections (AIFT)

Acute infections following transfusion can lead to prolonged hospitalizations, sepsis, septic shock, and death. Those most at risk include elderly and immunocompromised patients because of high utilization of blood products, comorbidities, and decreased immune function.

Among 8,833,817 stays, the overall rate per 100,000 stays was 2.1. The rate for immunocompromised patients was 5.4, compared with 1.2 for nonimmunocompromised patients, for a rate ratio of 4.4 (P less than .001).

The incidence rate declined significantly (P = .03) over the study period, with the 3 latest years having the lowest rates.

Rates increased substantially among immunocompromised patients by the number of units transfused, but remained relatively stable among nonimmunocompromised patients.

Infection rates declined with age, from 2.7 per 100,000 stays for patients aged 65-68 years to 1.2 per 100,000 for those aged 85 years and older.

As with other adverse events, AIFT rates were likely related to the blood components transfused, with substantially higher rates for stays during which platelets were transfused either alone or with RBCs, compared with RBCs alone. This could be caused by the room-temperature storage of platelets and higher number of platelets units transfused, compared with RBCs alone, especially among immunocompromised patients.

In all, 51.9% of AIFT cases also had sepsis noted in the medical record, indicating high severity and emphasizing the importance of AIFT prevention, Dr. Menis said.

The studies were funded by the FDA, and Dr. Menis is an FDA employee. He reported having no conflicts of interest.