Pulmonology

LJUBLJANA, SLOVENIA – Prevention or early effective treatment of respiratory syncytial virus (RSV) infection in infants and small children holds the promise of sharply reduced burdens of both acute otitis media (AOM) and pneumonia, Terho Heikkinen, MD, PhD, predicted in the Bill Marshall Award Lecture presented at the annual meeting of the European Society for Paediatric Infectious Diseases (ESPID).

RSV is by far the hottest virus in the world,” declared Dr. Heikkinen, professor of pediatrics at the University of Turku (Finland).

“A lot of progress is being made with respect to RSV. This increased understanding holds great promise for new interventions,” he explained. “Lots of different types of vaccines are being developed, monoclonal antibodies, antivirals. So there is a hope that within a number of years we will have interventions against RSV.”

Today influenza is the only respiratory viral infection that’s preventable via vaccine or effectively treatable using antiviral drugs. That situation has to change, as Dr. Heikkinen demonstrated early in his career; RSV is the respiratory virus that’s most likely to invade the middle ear during AOM. It’s much more ototropic than influenza, parainfluenza, enteroviruses, or adenoviruses (N Engl J Med. 1999 Jan 28;340[4]:260-4), he noted.

The Bill Marshall Award and Lecture, ESPID’s most prestigious award, is given annually to an individual recognized as having significantly advanced the field of pediatric infectious diseases. Dr. Heikkinen was singled out for his decades of work establishing that viruses, including RSV, play a key role in AOM, which had traditionally been regarded as a bacterial infection. He and his coinvestigators demonstrated that in about two-thirds of cases, AOM is actually caused by a combination of bacteria and viruses, which explains why patients’ clinical response to antibiotic therapy for AOM often is poor. They also described the chain of events whereby viral infection of the upper airway epithelium triggers an inflammatory response in the nasopharynx, with resultant Eustachian tube dysfunction and negative middle ear pressure, which in turn encourages microbial invasion of the middle ear. Moreover, they showed that the peak incidence of AOM isn’t on day 1 after onset of upper respiratory infection symptoms, but on day 3 or 4.

“What this tells us is that, once a child has a viral respiratory infection, there is a certain window of opportunity to try to prevent the development of the complication if we have the right tools in place,” Dr. Heikkinen said.

He and his colleagues put this lesson to good use nearly a decade ago in a randomized, double-blind trial in which they showed that giving oseltamivir (Tamiflu) within 12 hours after onset of influenza symptoms in children aged 1-3 years reduced the subsequent incidence of AOM by 85%, compared with placebo (Clin Infect Dis. 2010 Oct 15;51[8]:887-94).

These observations paved the way for the ongoing intensive research effort exploring ways of preventing AOM through interventions at two different levels: by developing viral vaccines to prevent a healthy child from contracting the viral upper respiratory infection that precedes AOM and by coming up with antiviral drugs or bacterial vaccines to prevent a upper respiratory infection from evolving into AOM.

The same applies to pneumonia. Other investigators showed years ago that both respiratory viruses and bacteria were present in two-thirds of sputum samples obtained from children with community-acquired pneumonia (Clin Microbiol Infect. 2012 Mar;18[3]:300-7).

RSV is the top cause of hospitalization for acute respiratory infection – pneumonia and bronchiolitis – in infants. Worldwide, it’s estimated that RSV accounts for more than 33 million episodes of pneumonia annually, with 3.2 million hospitalizations and 118,200 deaths.

Beyond the hospital, however, Dr. Heikkinen and colleagues conducted a prospective cohort study in Turku over the course of two consecutive respiratory infection seasons in which they captured the huge burden of RSV as an outpatient illness. It hit hardest in children younger than 3 years, in whom the average annual incidence of RSV infection was 275 cases per 1,000 children. In that youngest age population, RSV upper respiratory infection was followed by AOM 58% of the time, with antibiotics prescribed in 66% of the cases of this complication of RSV illness. The mean duration of RSV illness was greatest in this young age group, at 13 days, and it was associated with parental absenteeism from work at a rate of 136 days per 100 children with RSV illness.

Moreover, while AOM occurred less frequently in children aged 3-6 years, 46% of the cases were attributed to a preceding RSV infection, which led to antibiotic treatment nearly half of the time (J Infect Dis. 2017 Jan 1;215[1]:17-23). This documentation has spurred further efforts to develop RSV vaccines and antivirals.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Prevention or early effective treatment of respiratory syncytial virus (RSV) infection in infants and small children holds the promise of sharply reduced burdens of both acute otitis media (AOM) and pneumonia, Terho Heikkinen, MD, PhD, predicted in the Bill Marshall Award Lecture presented at the annual meeting of the European Society for Paediatric Infectious Diseases (ESPID).

RSV is by far the hottest virus in the world,” declared Dr. Heikkinen, professor of pediatrics at the University of Turku (Finland).

“A lot of progress is being made with respect to RSV. This increased understanding holds great promise for new interventions,” he explained. “Lots of different types of vaccines are being developed, monoclonal antibodies, antivirals. So there is a hope that within a number of years we will have interventions against RSV.”

Today influenza is the only respiratory viral infection that’s preventable via vaccine or effectively treatable using antiviral drugs. That situation has to change, as Dr. Heikkinen demonstrated early in his career; RSV is the respiratory virus that’s most likely to invade the middle ear during AOM. It’s much more ototropic than influenza, parainfluenza, enteroviruses, or adenoviruses (N Engl J Med. 1999 Jan 28;340[4]:260-4), he noted.

The Bill Marshall Award and Lecture, ESPID’s most prestigious award, is given annually to an individual recognized as having significantly advanced the field of pediatric infectious diseases. Dr. Heikkinen was singled out for his decades of work establishing that viruses, including RSV, play a key role in AOM, which had traditionally been regarded as a bacterial infection. He and his coinvestigators demonstrated that in about two-thirds of cases, AOM is actually caused by a combination of bacteria and viruses, which explains why patients’ clinical response to antibiotic therapy for AOM often is poor. They also described the chain of events whereby viral infection of the upper airway epithelium triggers an inflammatory response in the nasopharynx, with resultant Eustachian tube dysfunction and negative middle ear pressure, which in turn encourages microbial invasion of the middle ear. Moreover, they showed that the peak incidence of AOM isn’t on day 1 after onset of upper respiratory infection symptoms, but on day 3 or 4.

“What this tells us is that, once a child has a viral respiratory infection, there is a certain window of opportunity to try to prevent the development of the complication if we have the right tools in place,” Dr. Heikkinen said.

He and his colleagues put this lesson to good use nearly a decade ago in a randomized, double-blind trial in which they showed that giving oseltamivir (Tamiflu) within 12 hours after onset of influenza symptoms in children aged 1-3 years reduced the subsequent incidence of AOM by 85%, compared with placebo (Clin Infect Dis. 2010 Oct 15;51[8]:887-94).

These observations paved the way for the ongoing intensive research effort exploring ways of preventing AOM through interventions at two different levels: by developing viral vaccines to prevent a healthy child from contracting the viral upper respiratory infection that precedes AOM and by coming up with antiviral drugs or bacterial vaccines to prevent a upper respiratory infection from evolving into AOM.

The same applies to pneumonia. Other investigators showed years ago that both respiratory viruses and bacteria were present in two-thirds of sputum samples obtained from children with community-acquired pneumonia (Clin Microbiol Infect. 2012 Mar;18[3]:300-7).

RSV is the top cause of hospitalization for acute respiratory infection – pneumonia and bronchiolitis – in infants. Worldwide, it’s estimated that RSV accounts for more than 33 million episodes of pneumonia annually, with 3.2 million hospitalizations and 118,200 deaths.

Beyond the hospital, however, Dr. Heikkinen and colleagues conducted a prospective cohort study in Turku over the course of two consecutive respiratory infection seasons in which they captured the huge burden of RSV as an outpatient illness. It hit hardest in children younger than 3 years, in whom the average annual incidence of RSV infection was 275 cases per 1,000 children. In that youngest age population, RSV upper respiratory infection was followed by AOM 58% of the time, with antibiotics prescribed in 66% of the cases of this complication of RSV illness. The mean duration of RSV illness was greatest in this young age group, at 13 days, and it was associated with parental absenteeism from work at a rate of 136 days per 100 children with RSV illness.

Moreover, while AOM occurred less frequently in children aged 3-6 years, 46% of the cases were attributed to a preceding RSV infection, which led to antibiotic treatment nearly half of the time (J Infect Dis. 2017 Jan 1;215[1]:17-23). This documentation has spurred further efforts to develop RSV vaccines and antivirals.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Prevention or early effective treatment of respiratory syncytial virus (RSV) infection in infants and small children holds the promise of sharply reduced burdens of both acute otitis media (AOM) and pneumonia, Terho Heikkinen, MD, PhD, predicted in the Bill Marshall Award Lecture presented at the annual meeting of the European Society for Paediatric Infectious Diseases (ESPID).

RSV is by far the hottest virus in the world,” declared Dr. Heikkinen, professor of pediatrics at the University of Turku (Finland).

“A lot of progress is being made with respect to RSV. This increased understanding holds great promise for new interventions,” he explained. “Lots of different types of vaccines are being developed, monoclonal antibodies, antivirals. So there is a hope that within a number of years we will have interventions against RSV.”

Today influenza is the only respiratory viral infection that’s preventable via vaccine or effectively treatable using antiviral drugs. That situation has to change, as Dr. Heikkinen demonstrated early in his career; RSV is the respiratory virus that’s most likely to invade the middle ear during AOM. It’s much more ototropic than influenza, parainfluenza, enteroviruses, or adenoviruses (N Engl J Med. 1999 Jan 28;340[4]:260-4), he noted.

The Bill Marshall Award and Lecture, ESPID’s most prestigious award, is given annually to an individual recognized as having significantly advanced the field of pediatric infectious diseases. Dr. Heikkinen was singled out for his decades of work establishing that viruses, including RSV, play a key role in AOM, which had traditionally been regarded as a bacterial infection. He and his coinvestigators demonstrated that in about two-thirds of cases, AOM is actually caused by a combination of bacteria and viruses, which explains why patients’ clinical response to antibiotic therapy for AOM often is poor. They also described the chain of events whereby viral infection of the upper airway epithelium triggers an inflammatory response in the nasopharynx, with resultant Eustachian tube dysfunction and negative middle ear pressure, which in turn encourages microbial invasion of the middle ear. Moreover, they showed that the peak incidence of AOM isn’t on day 1 after onset of upper respiratory infection symptoms, but on day 3 or 4.

“What this tells us is that, once a child has a viral respiratory infection, there is a certain window of opportunity to try to prevent the development of the complication if we have the right tools in place,” Dr. Heikkinen said.

He and his colleagues put this lesson to good use nearly a decade ago in a randomized, double-blind trial in which they showed that giving oseltamivir (Tamiflu) within 12 hours after onset of influenza symptoms in children aged 1-3 years reduced the subsequent incidence of AOM by 85%, compared with placebo (Clin Infect Dis. 2010 Oct 15;51[8]:887-94).

These observations paved the way for the ongoing intensive research effort exploring ways of preventing AOM through interventions at two different levels: by developing viral vaccines to prevent a healthy child from contracting the viral upper respiratory infection that precedes AOM and by coming up with antiviral drugs or bacterial vaccines to prevent a upper respiratory infection from evolving into AOM.

The same applies to pneumonia. Other investigators showed years ago that both respiratory viruses and bacteria were present in two-thirds of sputum samples obtained from children with community-acquired pneumonia (Clin Microbiol Infect. 2012 Mar;18[3]:300-7).

RSV is the top cause of hospitalization for acute respiratory infection – pneumonia and bronchiolitis – in infants. Worldwide, it’s estimated that RSV accounts for more than 33 million episodes of pneumonia annually, with 3.2 million hospitalizations and 118,200 deaths.

Beyond the hospital, however, Dr. Heikkinen and colleagues conducted a prospective cohort study in Turku over the course of two consecutive respiratory infection seasons in which they captured the huge burden of RSV as an outpatient illness. It hit hardest in children younger than 3 years, in whom the average annual incidence of RSV infection was 275 cases per 1,000 children. In that youngest age population, RSV upper respiratory infection was followed by AOM 58% of the time, with antibiotics prescribed in 66% of the cases of this complication of RSV illness. The mean duration of RSV illness was greatest in this young age group, at 13 days, and it was associated with parental absenteeism from work at a rate of 136 days per 100 children with RSV illness.

Moreover, while AOM occurred less frequently in children aged 3-6 years, 46% of the cases were attributed to a preceding RSV infection, which led to antibiotic treatment nearly half of the time (J Infect Dis. 2017 Jan 1;215[1]:17-23). This documentation has spurred further efforts to develop RSV vaccines and antivirals.

bjancin@mdedge.com

A large Kaiser Permanente study paints a nuanced picture of the acellular pertussis vaccine, with more cases occurring in fully vaccinated children, but the highest risk of disease occurring among the under- and unvaccinated.

Sean Locke/iStockphoto

Among nearly half a million children, the unvaccinated were 13 times more likely to develop pertussis than fully vaccinated children, Ousseny Zerbo, PhD, of Kaiser Permanente Northern California in Oakland and colleagues wrote in Pediatrics. But 82% of cases occurred in fully vaccinated children and just 5% in undervaccinated children – and rates increased in both groups the farther they were in time from the last vaccination.

“Within our study population, greater than 80% of pertussis cases occurred among age-appropriately vaccinated children,” the team wrote. “Children who were further away from their last DTaP dose were at increased risk of pertussis, even after controlling for undervaccination. Our results suggest that, in this population, possibly in conjunction with other factors not addressed in this study, suboptimal vaccine efficacy and waning [immunity] played a major role in recent pertussis epidemics.”

The results are consistent with several prior studies, including one finding that the odds of the disease increased by 33% for every additional year after the third or fifth DTaP dose (Pediatrics. 2015;135[2]:331-43).

The current study comprised 469,982 children aged between 3 months and 11 years, who were followed for a mean of 4.6 years. Over the entire study period, there were 738 lab-confirmed pertussis cases. Most of these (515; 70%) occurred in fully vaccinated children. Another 99 (13%) occurred in unvaccinated children, 36 (5%) in undervaccinated children, and 88 (12%) in fully vaccinated plus one dose.

In a multivariate analysis, the risk of pertussis was 13 times higher among the unvaccinated (adjusted hazard ratio, 13) and almost 2 times higher among the undervaccinated (aHR, 1.9), compared with fully vaccinated children. Those who had been fully vaccinated and received a booster had the lowest risk, about half that of fully vaccinated children (aHR, 0.48).

Risk varied according to age, but also was significantly higher among unvaccinated children at each time point. Risk ranged from 4 times higher among those aged 3-5 months to 23 times higher among those aged 19-84 months. Undervaccinated children aged 5-7 months and 19-84 months also were at significantly increased risk for pertussis, compared with fully vaccinated children. Children who were fully vaccinated plus one dose had a significantly reduced risk at 7-19 months and at 19-84 months, compared with the fully vaccinated reference group.

“Across all follow-up and all age groups, VE [vaccine effectiveness] was 86% ... for undervaccinated children, compared with unvaccinated children,” Dr. Zerbo and associates wrote. “VE was even higher for fully vaccinated children [93%] and for those who were fully vaccinated plus one dose [96%].”

But VE waned as time progressed farther from the last DTaP dose. The multivariate model found more than a 100% increased risk for those whose last DTaP was at least 3 years past, compared with less than 1 year past (aHR, 2.58).

The model also found time-bound risk increases among fully vaccinated children, with a more than 300% increased risk among those at least 6 years out from the last DTaP dose, compared with 3 years out (aHR, 4.66).

The results indicate that other factors besides adherence to the recommended vaccine schedule may be at work in recent pertussis outbreaks.

“Although waning immunity is clearly an important factor driving pertussis epidemics in recent years, other factors that we did not evaluate in this study might also contribute to pertussis epidemics individually or in synergy,” Dr. Zerbo and associates wrote. “Results from studies in baboons suggest that the acellular pertussis vaccines are unable to prevent colonization, carriage, and transmission. If this is also true for humans, this could contribute to pertussis epidemics. The causes of recent pertussis epidemics are complex, and we were only able to address some aspects in our study.”

The study was funded by Kaiser Permanente Northern California, the National Institutes of Health, and in part by a National Institute of Allergy and Infectious Diseases grant. One coauthor reported receiving research grant support from Sanofi Pasteur, Novartis, GlaxoSmithKline, Merck, MedImmune, Pfizer, and Dynavax for unrelated studies; the other authors reported no relevant financial disclosures.

msullivan@mdedge.com

SOURCE: Zerbo O et al. Pediatrics. 2019 Jun 10. doi: 10.1542/peds.2018-3466.

A large Kaiser Permanente study paints a nuanced picture of the acellular pertussis vaccine, with more cases occurring in fully vaccinated children, but the highest risk of disease occurring among the under- and unvaccinated.

Sean Locke/iStockphoto

Among nearly half a million children, the unvaccinated were 13 times more likely to develop pertussis than fully vaccinated children, Ousseny Zerbo, PhD, of Kaiser Permanente Northern California in Oakland and colleagues wrote in Pediatrics. But 82% of cases occurred in fully vaccinated children and just 5% in undervaccinated children – and rates increased in both groups the farther they were in time from the last vaccination.

“Within our study population, greater than 80% of pertussis cases occurred among age-appropriately vaccinated children,” the team wrote. “Children who were further away from their last DTaP dose were at increased risk of pertussis, even after controlling for undervaccination. Our results suggest that, in this population, possibly in conjunction with other factors not addressed in this study, suboptimal vaccine efficacy and waning [immunity] played a major role in recent pertussis epidemics.”

The results are consistent with several prior studies, including one finding that the odds of the disease increased by 33% for every additional year after the third or fifth DTaP dose (Pediatrics. 2015;135[2]:331-43).

The current study comprised 469,982 children aged between 3 months and 11 years, who were followed for a mean of 4.6 years. Over the entire study period, there were 738 lab-confirmed pertussis cases. Most of these (515; 70%) occurred in fully vaccinated children. Another 99 (13%) occurred in unvaccinated children, 36 (5%) in undervaccinated children, and 88 (12%) in fully vaccinated plus one dose.

In a multivariate analysis, the risk of pertussis was 13 times higher among the unvaccinated (adjusted hazard ratio, 13) and almost 2 times higher among the undervaccinated (aHR, 1.9), compared with fully vaccinated children. Those who had been fully vaccinated and received a booster had the lowest risk, about half that of fully vaccinated children (aHR, 0.48).

Risk varied according to age, but also was significantly higher among unvaccinated children at each time point. Risk ranged from 4 times higher among those aged 3-5 months to 23 times higher among those aged 19-84 months. Undervaccinated children aged 5-7 months and 19-84 months also were at significantly increased risk for pertussis, compared with fully vaccinated children. Children who were fully vaccinated plus one dose had a significantly reduced risk at 7-19 months and at 19-84 months, compared with the fully vaccinated reference group.

“Across all follow-up and all age groups, VE [vaccine effectiveness] was 86% ... for undervaccinated children, compared with unvaccinated children,” Dr. Zerbo and associates wrote. “VE was even higher for fully vaccinated children [93%] and for those who were fully vaccinated plus one dose [96%].”

But VE waned as time progressed farther from the last DTaP dose. The multivariate model found more than a 100% increased risk for those whose last DTaP was at least 3 years past, compared with less than 1 year past (aHR, 2.58).

The model also found time-bound risk increases among fully vaccinated children, with a more than 300% increased risk among those at least 6 years out from the last DTaP dose, compared with 3 years out (aHR, 4.66).

The results indicate that other factors besides adherence to the recommended vaccine schedule may be at work in recent pertussis outbreaks.

“Although waning immunity is clearly an important factor driving pertussis epidemics in recent years, other factors that we did not evaluate in this study might also contribute to pertussis epidemics individually or in synergy,” Dr. Zerbo and associates wrote. “Results from studies in baboons suggest that the acellular pertussis vaccines are unable to prevent colonization, carriage, and transmission. If this is also true for humans, this could contribute to pertussis epidemics. The causes of recent pertussis epidemics are complex, and we were only able to address some aspects in our study.”

The study was funded by Kaiser Permanente Northern California, the National Institutes of Health, and in part by a National Institute of Allergy and Infectious Diseases grant. One coauthor reported receiving research grant support from Sanofi Pasteur, Novartis, GlaxoSmithKline, Merck, MedImmune, Pfizer, and Dynavax for unrelated studies; the other authors reported no relevant financial disclosures.

msullivan@mdedge.com

SOURCE: Zerbo O et al. Pediatrics. 2019 Jun 10. doi: 10.1542/peds.2018-3466.

A large Kaiser Permanente study paints a nuanced picture of the acellular pertussis vaccine, with more cases occurring in fully vaccinated children, but the highest risk of disease occurring among the under- and unvaccinated.

Sean Locke/iStockphoto

Among nearly half a million children, the unvaccinated were 13 times more likely to develop pertussis than fully vaccinated children, Ousseny Zerbo, PhD, of Kaiser Permanente Northern California in Oakland and colleagues wrote in Pediatrics. But 82% of cases occurred in fully vaccinated children and just 5% in undervaccinated children – and rates increased in both groups the farther they were in time from the last vaccination.

“Within our study population, greater than 80% of pertussis cases occurred among age-appropriately vaccinated children,” the team wrote. “Children who were further away from their last DTaP dose were at increased risk of pertussis, even after controlling for undervaccination. Our results suggest that, in this population, possibly in conjunction with other factors not addressed in this study, suboptimal vaccine efficacy and waning [immunity] played a major role in recent pertussis epidemics.”

The results are consistent with several prior studies, including one finding that the odds of the disease increased by 33% for every additional year after the third or fifth DTaP dose (Pediatrics. 2015;135[2]:331-43).

The current study comprised 469,982 children aged between 3 months and 11 years, who were followed for a mean of 4.6 years. Over the entire study period, there were 738 lab-confirmed pertussis cases. Most of these (515; 70%) occurred in fully vaccinated children. Another 99 (13%) occurred in unvaccinated children, 36 (5%) in undervaccinated children, and 88 (12%) in fully vaccinated plus one dose.

In a multivariate analysis, the risk of pertussis was 13 times higher among the unvaccinated (adjusted hazard ratio, 13) and almost 2 times higher among the undervaccinated (aHR, 1.9), compared with fully vaccinated children. Those who had been fully vaccinated and received a booster had the lowest risk, about half that of fully vaccinated children (aHR, 0.48).

Risk varied according to age, but also was significantly higher among unvaccinated children at each time point. Risk ranged from 4 times higher among those aged 3-5 months to 23 times higher among those aged 19-84 months. Undervaccinated children aged 5-7 months and 19-84 months also were at significantly increased risk for pertussis, compared with fully vaccinated children. Children who were fully vaccinated plus one dose had a significantly reduced risk at 7-19 months and at 19-84 months, compared with the fully vaccinated reference group.

“Across all follow-up and all age groups, VE [vaccine effectiveness] was 86% ... for undervaccinated children, compared with unvaccinated children,” Dr. Zerbo and associates wrote. “VE was even higher for fully vaccinated children [93%] and for those who were fully vaccinated plus one dose [96%].”

But VE waned as time progressed farther from the last DTaP dose. The multivariate model found more than a 100% increased risk for those whose last DTaP was at least 3 years past, compared with less than 1 year past (aHR, 2.58).

The model also found time-bound risk increases among fully vaccinated children, with a more than 300% increased risk among those at least 6 years out from the last DTaP dose, compared with 3 years out (aHR, 4.66).

The results indicate that other factors besides adherence to the recommended vaccine schedule may be at work in recent pertussis outbreaks.

“Although waning immunity is clearly an important factor driving pertussis epidemics in recent years, other factors that we did not evaluate in this study might also contribute to pertussis epidemics individually or in synergy,” Dr. Zerbo and associates wrote. “Results from studies in baboons suggest that the acellular pertussis vaccines are unable to prevent colonization, carriage, and transmission. If this is also true for humans, this could contribute to pertussis epidemics. The causes of recent pertussis epidemics are complex, and we were only able to address some aspects in our study.”

The study was funded by Kaiser Permanente Northern California, the National Institutes of Health, and in part by a National Institute of Allergy and Infectious Diseases grant. One coauthor reported receiving research grant support from Sanofi Pasteur, Novartis, GlaxoSmithKline, Merck, MedImmune, Pfizer, and Dynavax for unrelated studies; the other authors reported no relevant financial disclosures.

msullivan@mdedge.com

SOURCE: Zerbo O et al. Pediatrics. 2019 Jun 10. doi: 10.1542/peds.2018-3466.

Measles cases in the United States have topped 1,000 for the first time since 1992, according to the Centers for Disease Control and Prevention.

The 41 new cases reported for the week ending June 6 bring the total for the year to 1,022, the CDC reported June 10, and that is more than any year since 1992, when there were 2,237 cases.

Idaho and Virginia reported their first cases of 2019, which makes a total of 28 states with measles cases this year. The Idaho case was reported in Latah County and is the state’s first since 2001. In Virginia, health officials are investigating possible contacts with an infected individual at Dulles International Airport and two other locations on June 2 and 4.

Outbreaks in Georgia, Maryland, and Michigan have ended, while seven others continue in California (Butte, Los Angeles, and Sacramento Counties), New York (Rockland County and New York City), Pennsylvania, and Washington, the CDC said. New York City has the largest outbreak this year with 509 cases through June 3, most of them occurring in Brooklyn.

rfranki@mdedge.com

Measles cases in the United States have topped 1,000 for the first time since 1992, according to the Centers for Disease Control and Prevention.

The 41 new cases reported for the week ending June 6 bring the total for the year to 1,022, the CDC reported June 10, and that is more than any year since 1992, when there were 2,237 cases.

Idaho and Virginia reported their first cases of 2019, which makes a total of 28 states with measles cases this year. The Idaho case was reported in Latah County and is the state’s first since 2001. In Virginia, health officials are investigating possible contacts with an infected individual at Dulles International Airport and two other locations on June 2 and 4.

Outbreaks in Georgia, Maryland, and Michigan have ended, while seven others continue in California (Butte, Los Angeles, and Sacramento Counties), New York (Rockland County and New York City), Pennsylvania, and Washington, the CDC said. New York City has the largest outbreak this year with 509 cases through June 3, most of them occurring in Brooklyn.

rfranki@mdedge.com

Measles cases in the United States have topped 1,000 for the first time since 1992, according to the Centers for Disease Control and Prevention.

The 41 new cases reported for the week ending June 6 bring the total for the year to 1,022, the CDC reported June 10, and that is more than any year since 1992, when there were 2,237 cases.

Idaho and Virginia reported their first cases of 2019, which makes a total of 28 states with measles cases this year. The Idaho case was reported in Latah County and is the state’s first since 2001. In Virginia, health officials are investigating possible contacts with an infected individual at Dulles International Airport and two other locations on June 2 and 4.

Outbreaks in Georgia, Maryland, and Michigan have ended, while seven others continue in California (Butte, Los Angeles, and Sacramento Counties), New York (Rockland County and New York City), Pennsylvania, and Washington, the CDC said. New York City has the largest outbreak this year with 509 cases through June 3, most of them occurring in Brooklyn.

rfranki@mdedge.com

ILLUSTRATIVE CASE

Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?

PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.² Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.³

The use of a diagnostic algorithm that includes the Wells’ criteria and a D-dimer concentration can exclude PE without CTPA in 20% to 30% of patients.⁴ However, due to the complexity of the algorithm and insufficient time in busy emergency departments, adherence to recommended diagnostic strategies is variable.⁵

Further, it is common for a D-dimer test to be obtained before clinical assessment by a provider.⁶ A fixed cutoff D-dimer concentration of 500 ng/mL is commonly used despite an absolute reduction of 11.6% (95% confidence interval [CI], 10.5-12.9) in the need for CTPA using an age-adjusted D-dimer concentration threshold (age × 10 ng/mL for patients > 50 years).⁷

Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.⁸ The development of a more efficient algorithm based on these 3 items that uses differential D-dimer concentration thresholds could retain sensitivity and decrease unnecessary CTPAs. Decreasing CTPAs would avoid contrast-induced nephropathy and decrease cancers associated with radiation exposure.^9-11 Significant cost savings could also be achieved, as the estimated cost of one CTPA is $648, while a D-dimer concentration is estimated to cost $14.¹²

STUDY SUMMARY

Simplified algorithm diagnoses PE with fewer CTPAs

The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.¹ After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a D-dimer concentration in all patients and assessment using the YEARS clinical decision rule, consisting of 3 items assessed by an attending physician: clinical signs of deep vein thrombosis, hemoptysis, and whether PE was the most likely diagnosis. PE was considered excluded if a patient had no positive YEARS items and a D-dimer concentration < 1000 ng/mL or if the patient had one or more YEARS items and a D-dimer concentration < 500 ng/mL. The primary outcome was venous thromboembolism (VTE) events at 3 months’ follow-up once PE was excluded. The secondary outcome was the number of required CTPAs using the YEARS decision rule compared with the number that would have been required if the Wells’ diagnostic algorithm had been implemented.

Of the 1743 patients who had none of the 3 YEARS items, 1320 had a D-dimer concentration below the 1000 ng/mL threshold. Fifty-five of the 423 who had a D-dimer ≥ 1000 ng/mL had confirmed PE by CTPA. In the 1722 patients who had at least 1 YEARS item, 1391 had a D-dimer concentration ≥ 500 ng/mL threshold; 401 of those 1391 had PE confirmed by CTPA.

Continue to: Eighteen of the 2964 patients...

Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.¹³ Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.¹⁴

The new diagnostic algorithm reduced the use of CT pulmonary angiography by 14% and produced a cost savings of $309,096.

Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.

WHAT’S NEW

High-level evidence says 14% fewer CTPAs

The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed D-dimer threshold of < 500 ng/mL.

CAVEATS

No adjusting D-dimer for age

The YEARS criteria does not consider an age-adjusted D-dimer threshold, which has been shown to further decrease CTPA use.⁶ This does not preclude the use of YEARS criteria; applying age-adjusted D-dimer thresholds would have led to an absolute reduction of 8.7% (95% CI, 6.4-11) in CTPAs.⁷

CHALLENGES TO IMPLEMENTATION

None to speak of

We see no challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?

PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.² Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.³

The use of a diagnostic algorithm that includes the Wells’ criteria and a D-dimer concentration can exclude PE without CTPA in 20% to 30% of patients.⁴ However, due to the complexity of the algorithm and insufficient time in busy emergency departments, adherence to recommended diagnostic strategies is variable.⁵

Further, it is common for a D-dimer test to be obtained before clinical assessment by a provider.⁶ A fixed cutoff D-dimer concentration of 500 ng/mL is commonly used despite an absolute reduction of 11.6% (95% confidence interval [CI], 10.5-12.9) in the need for CTPA using an age-adjusted D-dimer concentration threshold (age × 10 ng/mL for patients > 50 years).⁷

Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.⁸ The development of a more efficient algorithm based on these 3 items that uses differential D-dimer concentration thresholds could retain sensitivity and decrease unnecessary CTPAs. Decreasing CTPAs would avoid contrast-induced nephropathy and decrease cancers associated with radiation exposure.^9-11 Significant cost savings could also be achieved, as the estimated cost of one CTPA is $648, while a D-dimer concentration is estimated to cost $14.¹²

STUDY SUMMARY

Simplified algorithm diagnoses PE with fewer CTPAs

The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.¹ After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a D-dimer concentration in all patients and assessment using the YEARS clinical decision rule, consisting of 3 items assessed by an attending physician: clinical signs of deep vein thrombosis, hemoptysis, and whether PE was the most likely diagnosis. PE was considered excluded if a patient had no positive YEARS items and a D-dimer concentration < 1000 ng/mL or if the patient had one or more YEARS items and a D-dimer concentration < 500 ng/mL. The primary outcome was venous thromboembolism (VTE) events at 3 months’ follow-up once PE was excluded. The secondary outcome was the number of required CTPAs using the YEARS decision rule compared with the number that would have been required if the Wells’ diagnostic algorithm had been implemented.

Of the 1743 patients who had none of the 3 YEARS items, 1320 had a D-dimer concentration below the 1000 ng/mL threshold. Fifty-five of the 423 who had a D-dimer ≥ 1000 ng/mL had confirmed PE by CTPA. In the 1722 patients who had at least 1 YEARS item, 1391 had a D-dimer concentration ≥ 500 ng/mL threshold; 401 of those 1391 had PE confirmed by CTPA.

Continue to: Eighteen of the 2964 patients...

Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.¹³ Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.¹⁴

The new diagnostic algorithm reduced the use of CT pulmonary angiography by 14% and produced a cost savings of $309,096.

Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.

WHAT’S NEW

High-level evidence says 14% fewer CTPAs

The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed D-dimer threshold of < 500 ng/mL.

CAVEATS

No adjusting D-dimer for age

The YEARS criteria does not consider an age-adjusted D-dimer threshold, which has been shown to further decrease CTPA use.⁶ This does not preclude the use of YEARS criteria; applying age-adjusted D-dimer thresholds would have led to an absolute reduction of 8.7% (95% CI, 6.4-11) in CTPAs.⁷

CHALLENGES TO IMPLEMENTATION

None to speak of

We see no challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?

PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.² Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.³

The use of a diagnostic algorithm that includes the Wells’ criteria and a D-dimer concentration can exclude PE without CTPA in 20% to 30% of patients.⁴ However, due to the complexity of the algorithm and insufficient time in busy emergency departments, adherence to recommended diagnostic strategies is variable.⁵

Further, it is common for a D-dimer test to be obtained before clinical assessment by a provider.⁶ A fixed cutoff D-dimer concentration of 500 ng/mL is commonly used despite an absolute reduction of 11.6% (95% confidence interval [CI], 10.5-12.9) in the need for CTPA using an age-adjusted D-dimer concentration threshold (age × 10 ng/mL for patients > 50 years).⁷

Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.⁸ The development of a more efficient algorithm based on these 3 items that uses differential D-dimer concentration thresholds could retain sensitivity and decrease unnecessary CTPAs. Decreasing CTPAs would avoid contrast-induced nephropathy and decrease cancers associated with radiation exposure.^9-11 Significant cost savings could also be achieved, as the estimated cost of one CTPA is $648, while a D-dimer concentration is estimated to cost $14.¹²

STUDY SUMMARY

Simplified algorithm diagnoses PE with fewer CTPAs

The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.¹ After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a D-dimer concentration in all patients and assessment using the YEARS clinical decision rule, consisting of 3 items assessed by an attending physician: clinical signs of deep vein thrombosis, hemoptysis, and whether PE was the most likely diagnosis. PE was considered excluded if a patient had no positive YEARS items and a D-dimer concentration < 1000 ng/mL or if the patient had one or more YEARS items and a D-dimer concentration < 500 ng/mL. The primary outcome was venous thromboembolism (VTE) events at 3 months’ follow-up once PE was excluded. The secondary outcome was the number of required CTPAs using the YEARS decision rule compared with the number that would have been required if the Wells’ diagnostic algorithm had been implemented.

Of the 1743 patients who had none of the 3 YEARS items, 1320 had a D-dimer concentration below the 1000 ng/mL threshold. Fifty-five of the 423 who had a D-dimer ≥ 1000 ng/mL had confirmed PE by CTPA. In the 1722 patients who had at least 1 YEARS item, 1391 had a D-dimer concentration ≥ 500 ng/mL threshold; 401 of those 1391 had PE confirmed by CTPA.

Continue to: Eighteen of the 2964 patients...

Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.¹³ Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.¹⁴

The new diagnostic algorithm reduced the use of CT pulmonary angiography by 14% and produced a cost savings of $309,096.

Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.

WHAT’S NEW

High-level evidence says 14% fewer CTPAs

The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed D-dimer threshold of < 500 ng/mL.

CAVEATS

No adjusting D-dimer for age

The YEARS criteria does not consider an age-adjusted D-dimer threshold, which has been shown to further decrease CTPA use.⁶ This does not preclude the use of YEARS criteria; applying age-adjusted D-dimer thresholds would have led to an absolute reduction of 8.7% (95% CI, 6.4-11) in CTPAs.⁷

CHALLENGES TO IMPLEMENTATION

None to speak of

We see no challenges to the implementation of this recommendation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

The Food and Drug Administration has approved two new formulations for the anti–interleukin-5 biologic mepolizumab (Nucala) for treatment of certain severe or rare forms of asthma, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.

The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.

The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.

Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.

cpalmer@mdedge.com

The Food and Drug Administration has approved two new formulations for the anti–interleukin-5 biologic mepolizumab (Nucala) for treatment of certain severe or rare forms of asthma, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.

The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.

The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.

Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.

cpalmer@mdedge.com

The Food and Drug Administration has approved two new formulations for the anti–interleukin-5 biologic mepolizumab (Nucala) for treatment of certain severe or rare forms of asthma, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.

The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.

The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.

Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.

cpalmer@mdedge.com

BALTIMORE – Pediatricians appear less comfortable discussing e-cigarettes and their harms with adolescents and parents than they do discussing dangers of tobacco products, according to a recent study.

LiudmylaSupynska/Thinkstock

“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.

A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.

Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.

Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.

The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.

Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.

Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.

Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).

Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).

Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).

Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).

The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).

Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).

More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).

The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.

The researchers noted no external funding or disclosures.

BALTIMORE – Pediatricians appear less comfortable discussing e-cigarettes and their harms with adolescents and parents than they do discussing dangers of tobacco products, according to a recent study.

LiudmylaSupynska/Thinkstock

“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.

A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.

Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.

Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.

The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.

Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.

Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.

Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).

Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).

Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).

Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).

The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).

Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).

More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).

The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.

The researchers noted no external funding or disclosures.

BALTIMORE – Pediatricians appear less comfortable discussing e-cigarettes and their harms with adolescents and parents than they do discussing dangers of tobacco products, according to a recent study.

LiudmylaSupynska/Thinkstock

“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.

A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.

Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.

Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.

The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.

Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.

Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.

Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).

Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).

Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).

Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).

The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).

Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).

More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).

The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.

The researchers noted no external funding or disclosures.

The Food and Drug Administration has approved a new indication for Zerbaxa (ceftolozane and tazobactam), authorizing it for the treatment of both hospital-acquired and ventilator-associated bacterial pneumonia.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The new indication is for patients 18 years and older. It was based on results of a multinational, double-blind study that compared Zerbaxa with a different antibacterial drug in 726 patients hospitalized with hospital-acquired/ventilator-associated bacterial pneumonia. Mortality and cure rates were similar in the Zerbaxa and comparator groups.

The most common adverse events observed in the trial were elevated liver enzyme levels, renal impairment or failure, and diarrhea. Patients with hypersensitivity to beta-lactam drugs should not be receive Zerbaxa.

“A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections. Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. ... That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections,” said Amy Abernethy, MD, PhD, the FDA’s principal deputy commissioner.

Zerbaxa was initially approved in 2014 for treatment of complicated intra-abdominal and urinary tract infections.

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved a new indication for Zerbaxa (ceftolozane and tazobactam), authorizing it for the treatment of both hospital-acquired and ventilator-associated bacterial pneumonia.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The new indication is for patients 18 years and older. It was based on results of a multinational, double-blind study that compared Zerbaxa with a different antibacterial drug in 726 patients hospitalized with hospital-acquired/ventilator-associated bacterial pneumonia. Mortality and cure rates were similar in the Zerbaxa and comparator groups.

The most common adverse events observed in the trial were elevated liver enzyme levels, renal impairment or failure, and diarrhea. Patients with hypersensitivity to beta-lactam drugs should not be receive Zerbaxa.

“A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections. Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. ... That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections,” said Amy Abernethy, MD, PhD, the FDA’s principal deputy commissioner.

Zerbaxa was initially approved in 2014 for treatment of complicated intra-abdominal and urinary tract infections.

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved a new indication for Zerbaxa (ceftolozane and tazobactam), authorizing it for the treatment of both hospital-acquired and ventilator-associated bacterial pneumonia.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The new indication is for patients 18 years and older. It was based on results of a multinational, double-blind study that compared Zerbaxa with a different antibacterial drug in 726 patients hospitalized with hospital-acquired/ventilator-associated bacterial pneumonia. Mortality and cure rates were similar in the Zerbaxa and comparator groups.

The most common adverse events observed in the trial were elevated liver enzyme levels, renal impairment or failure, and diarrhea. Patients with hypersensitivity to beta-lactam drugs should not be receive Zerbaxa.

“A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections. Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. ... That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections,” said Amy Abernethy, MD, PhD, the FDA’s principal deputy commissioner.

Zerbaxa was initially approved in 2014 for treatment of complicated intra-abdominal and urinary tract infections.

Find the full press release on the FDA website.

lfranki@mdedge.com

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

LJUBLJANA, SLOVENIA – A “surprisingly low” prevalence of protective antibodies against measles is present in adolescents and adults living with HIV infection despite their prior vaccination against the resurgent disease, Raquel M. Simakawa, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“With the present concern about the global reemergence of measles, we should consider measuring measles antibodies in people living with HIV, especially those who acquired the infection vertically, and then revaccinating those with low titers,” said Dr. Simakawa of the Federal University of São Paolo.

She presented interim findings of an ongoing study of the measles immunologic status of persons living with HIV, which for this analysis included 57 patients who acquired HIV from their mother via vertical transmission and 24 with horizontally acquired HIV. The vertical-transmission group was significantly younger, with a median age of 20 years, compared with 31 years in the horizontal group, who were diagnosed with HIV infection at an average age of 24 years. The vast majority of subjects were on combination antiretroviral therapy. No detectable HIV viral load had been present for a median of 70 months in the vertical group and 25 months in the horizontal group.

Only a mere 7% of the vertical transmission group had protective levels of measles IgG antibodies as measured by enzyme-linked immunosorbent assay, as did 29% of the horizontal group. The likely explanation for the higher rate of protection in the horizontal group, she said, is that they received their routine measles vaccination before they acquired HIV infection, and some of them didn’t lose their protective antibodies during their immune system’s fight against HIV infection.

Session chair Nico G. Hartwig, MD, of Franciscus Hospital in Rotterdam, the Netherlands, posed a question: Given the sky-high rate of measles seronegativity status among the vertically transmitted HIV-positive group – the patient population pediatricians focus on – why bother to measure their measles antibody level? Why not just give them all a measles booster?

Dr. Simakawa replied that that’s worth considering in routine clinical practice now that her study has shown that this group is more vulnerable to measles because of their poor response to immunization. But the study is ongoing, with larger numbers of patients to be enrolled. Also, in the second phase of the study, which will include a control group, measles IgG antibodies will be remeasured 1 month after administration of a new dose of measles vaccine.

She reported having no financial conflicts regarding this study, conducted free of commercial support.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – A “surprisingly low” prevalence of protective antibodies against measles is present in adolescents and adults living with HIV infection despite their prior vaccination against the resurgent disease, Raquel M. Simakawa, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“With the present concern about the global reemergence of measles, we should consider measuring measles antibodies in people living with HIV, especially those who acquired the infection vertically, and then revaccinating those with low titers,” said Dr. Simakawa of the Federal University of São Paolo.

She presented interim findings of an ongoing study of the measles immunologic status of persons living with HIV, which for this analysis included 57 patients who acquired HIV from their mother via vertical transmission and 24 with horizontally acquired HIV. The vertical-transmission group was significantly younger, with a median age of 20 years, compared with 31 years in the horizontal group, who were diagnosed with HIV infection at an average age of 24 years. The vast majority of subjects were on combination antiretroviral therapy. No detectable HIV viral load had been present for a median of 70 months in the vertical group and 25 months in the horizontal group.

Only a mere 7% of the vertical transmission group had protective levels of measles IgG antibodies as measured by enzyme-linked immunosorbent assay, as did 29% of the horizontal group. The likely explanation for the higher rate of protection in the horizontal group, she said, is that they received their routine measles vaccination before they acquired HIV infection, and some of them didn’t lose their protective antibodies during their immune system’s fight against HIV infection.

Session chair Nico G. Hartwig, MD, of Franciscus Hospital in Rotterdam, the Netherlands, posed a question: Given the sky-high rate of measles seronegativity status among the vertically transmitted HIV-positive group – the patient population pediatricians focus on – why bother to measure their measles antibody level? Why not just give them all a measles booster?

Dr. Simakawa replied that that’s worth considering in routine clinical practice now that her study has shown that this group is more vulnerable to measles because of their poor response to immunization. But the study is ongoing, with larger numbers of patients to be enrolled. Also, in the second phase of the study, which will include a control group, measles IgG antibodies will be remeasured 1 month after administration of a new dose of measles vaccine.

She reported having no financial conflicts regarding this study, conducted free of commercial support.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – A “surprisingly low” prevalence of protective antibodies against measles is present in adolescents and adults living with HIV infection despite their prior vaccination against the resurgent disease, Raquel M. Simakawa, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“With the present concern about the global reemergence of measles, we should consider measuring measles antibodies in people living with HIV, especially those who acquired the infection vertically, and then revaccinating those with low titers,” said Dr. Simakawa of the Federal University of São Paolo.

She presented interim findings of an ongoing study of the measles immunologic status of persons living with HIV, which for this analysis included 57 patients who acquired HIV from their mother via vertical transmission and 24 with horizontally acquired HIV. The vertical-transmission group was significantly younger, with a median age of 20 years, compared with 31 years in the horizontal group, who were diagnosed with HIV infection at an average age of 24 years. The vast majority of subjects were on combination antiretroviral therapy. No detectable HIV viral load had been present for a median of 70 months in the vertical group and 25 months in the horizontal group.

Only a mere 7% of the vertical transmission group had protective levels of measles IgG antibodies as measured by enzyme-linked immunosorbent assay, as did 29% of the horizontal group. The likely explanation for the higher rate of protection in the horizontal group, she said, is that they received their routine measles vaccination before they acquired HIV infection, and some of them didn’t lose their protective antibodies during their immune system’s fight against HIV infection.

Session chair Nico G. Hartwig, MD, of Franciscus Hospital in Rotterdam, the Netherlands, posed a question: Given the sky-high rate of measles seronegativity status among the vertically transmitted HIV-positive group – the patient population pediatricians focus on – why bother to measure their measles antibody level? Why not just give them all a measles booster?

Dr. Simakawa replied that that’s worth considering in routine clinical practice now that her study has shown that this group is more vulnerable to measles because of their poor response to immunization. But the study is ongoing, with larger numbers of patients to be enrolled. Also, in the second phase of the study, which will include a control group, measles IgG antibodies will be remeasured 1 month after administration of a new dose of measles vaccine.

She reported having no financial conflicts regarding this study, conducted free of commercial support.

bjancin@mdedge.com

From Tufts Medical Center, Boston, MA.

Abstract

• Objective: Audits at our academic medical center revealed near 100% compliance with protocols for perioperative venous thromboembolism (VTE) prophylaxis, but recent National Surgical Quality Improvement Program data demonstrated a higher than expected incidence of VTE (observed/expected = 1.32). The objective of this study was to identify potential causes of this discrepancy.
• Design: Retrospective case-control study.
• Setting: Urban academic medical center with high case-mix indices (Medicare approximately 2.4, non-Medicare approximately 2.0).
• Participants: 102 surgical inpatients with VTE (September 2012 to October 2015) matched with controls for age, gender, and type of procedure.
• Measurements: Prevalence of common VTE risk factors, length of stay, number of procedures, index operation times, and postoperative bed rest > 12 hours were assessed. Utilization of and compliance with our VTE risk assessment tool was also investigated.
• Results: Cases underwent more procedures and had longer lengths of stay and index procedures than controls. In addition, cases were more likely to have had > 12 hours of postoperative bed rest and central venous access than controls. Cases had more infections and were more likely to have severe lung disease, thrombophilia, and a history of prior VTE than controls. No differences in body mass index, tobacco use, current or previous malignancy, or VTE risk assessment form use were observed. Overall, care complexity and risk factors were equally important in determining VTE incidence. Our analyses also revealed lack of strict adherence to our VTE risk stratification protocol and frequent use of suboptimal prophylactic regimens.
• Conclusion: Well-accepted risk factors and overall care complexity determine VTE risk. Preventing VTE in high-risk patients requires assiduous attention to detail in VTE risk assessment and in delivery of optimal prophylaxis. Patients at especially high risk may require customized prophylactic regimens.

Keywords: hospital-acquired venous thromboembolic disease; VTE prophylaxis, surgical patients.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are well-recognized causes of morbidity and mortality in surgical patients. Between 350,000 and 600,000 cases of venous thromboembolism (VTE) occur each year in the United States, and it is responsible for approximately 10% of preventable in-hospital fatalities.^1-3 Given VTE’s impact on patients and the healthcare system and the fact that it is preventable, intense effort has been focused on developing more effective prophylactic measures to decrease its incidence.^2-4 In 2008, the surgeon general issued a “call to action” for increased efforts to prevent VTE.⁵

The American College of Chest Physicians (ACCP) guidelines subcategorize patients based on type of surgery. In addition, the ACCP guidelines support the use of a Caprini-based scoring system to aid in risk stratification and improve clinical decision-making (Table 1).^4,6-9 In general, scores ≥ 5 qualify individuals as high risk. Based on their risk category, patients receive mechanical prophylaxis, chemical prophylaxis, or a combination of the 2. Lower-risk patients who are ambulatory typically receive only mechanical prophylaxis while in bed, whereas higher-risk patients receive a combination of mechanical prophylaxis and chemoprophylaxis measures.⁷ In general, low-molecular-weight heparin (40 mg daily) and low-dose unfractionated heparin (5000 units 3 times daily) have been the standard evidence-based options for chemoprophylaxis in surgical patients. Absolute contraindications for prophylaxis include active bleeding and known increased risk of bleeding based on patient- or procedure-specific factors.

Our hospital, a 350-bed academic medical center in downtown Boston, MA, serving a diverse population with a very high case-mix index (2.4 Medicare and 2.0 non-Medicare), has strict protocols for VTE prophylaxis consistent with the ACCP guidelines and based on the Surgical Care Improvement Project (SCIP) measures published in 2006.¹⁰ The SCIP mandates allow for considerable surgeon discretion in the use of chemoprophylaxis for neurosurgical cases and general and orthopedic surgery cases deemed to be at high risk for bleeding. In addition, SCIP requires only that prophylaxis be initiated within 24 hours of surgical end time. Although recent audits revealed nearly 100% compliance with SCIP-mandated protocols, National Surgical Quality Improvement Program (NSQIP) data showed that the incidence of VTE events at our institution was higher than expected (observed/expected [O/E] = 1.32).

In order to determine the reasons for this mismatch between process and outcome performance, we investigated whether there were characteristics of our patient population that contributed to the higher than expected rates of VTE, and we scrutinized our VTE prophylaxis protocol to determine if there were aspects of our process that were also contributory.

Methods

Study Sample

This is a retrospective case-control study of surgical inpatients at our hospital during the period September 2012 to October 2015. Cases were identified as patients diagnosed with a VTE (DVT or PE). Controls were identified from a pool of surgical patients whose courses were not complicated by VTE during the same time frame as the cases and who were matched as closely as possible by procedure code, age, and gender.

 

 

Variables

Patient and hospital course variables that were analyzed included demographics, comorbidities, length of stay, number of procedures, index operation times, duration of postoperative bed rest, use of mechanical prophylaxis, and type of chemoprophylaxis and time frame within which it was initiated. Data were collected via chart review using International Classification of Diseases-9 and -10 codes to identify surgical cases within the allotted time period who were diagnosed with VTE. Demographic variables included age, sex, and ethnicity. Comorbidities included hypertension, diabetes, coronary artery disease, serious lung disease, previous or current malignancy, documented hypercoagulable state, and previous history of VTE. Body mass index (BMI) was also recorded. The aforementioned disease-specific variables were not matched between the case and control groups, as this data was obtained retrospectively during data collection.

Analysis

Associations between case and matched control were analyzed using the paired t-test for continuous variables and McNemar’s test for categorical variables. P values < 0.05 were considered statistically significant. SAS Enterprise Guide 7.15 (Cary, NC) was used for all statistical analyses.

The requirement for informed consent was waived by our Institutional Review Board, as the study was initially deemed to be a quality improvement project, and all data used for this report were de-identified.

Results

Our retrospective case-control analysis included a sample of 102 surgical patients whose courses were complicated by VTE between September 2012 and October 2015. The cases were distributed among 6 different surgical categories (Figure 1): trauma (20%), cancer (10%), cardiovascular (21%), noncancer neurosurgery (28%), elective orthopedics (11%), and miscellaneous general surgery (10%).

Comparisons between cases and controls in terms of patient demographics and risk factors are shown in Table 2. No statistically significant difference was observed in ethnicity or race between the 2 groups. Overall, cases had more hip/pelvis/leg fractures at presentation (P = 0.0008). The case group also had higher proportions of patients with postoperative bed rest greater than 12 hours (P = 0.009), central venous access (P < 0.0001), infection (P < 0.0001), and lower extremity edema documented during the hospitalization prior to development of DVT (P < 0.0001). Additionally, cases had significantly greater rates of previous VTE (P = 0.0004), inherited or acquired thrombophilia (P = 0.03), history of stroke (P = 0.0003), and severe lung disease, including pneumonia (P = 0.0008). No significant differences were noted between cases and matched controls in BMI (P = 0.43), current tobacco use (P = 0.71), current malignancy (P = 0.80), previous malignancy (P = 0.83), head trauma (P = 0.17), or acute cardiac disease (myocardial infarction or congestive heart failure; P = 0.12).

Variables felt to indicate overall complexity of hospital course for cases as compared to controls are outlined in Table 3. Cases were found to have significantly longer lengths of stay (median, 15.5 days versus 3 days, P < 0.0001). To account for the possibility that the development of VTE contributed to the increased length of stay in the cases, we also looked at the duration between admission date and the date of VTE diagnosis and determined that cases still had a longer length of stay when this was accounted for (median, 7 days versus 3 days, P < 0.0001). A much higher proportion of cases underwent more than 1 procedure compared to controls (P < 0.0001), and cases had significantly longer index operations as compared to controls (P = 0.002).

Seventeen cases received heparin on induction during their index procedure, compared to 23 controls (P = 0.24). Additionally, 63 cases began a prophylaxis regimen within 24 hours of surgery end time, compared to 68 controls (P = 0.24). The chemoprophylactic regimens utilized in cases and in controls are summarized in Figure 2. Of note, only 26 cases and 32 controls received standard prophylactic regimens with no missed doses (heparin 5000 units 3 times daily or enoxaparin 40 mg daily). Additionally, in over half of cases and a third of controls, nonstandard regimens were ordered. Examples of nonstandard regimens included nonstandard heparin or enoxaparin doses, low-dose warfarin, or aspirin alone. In most cases, nonstandard regimens were justified on the basis of high risk for bleeding.

Mechanical prophylaxis with pneumatic sequential compression devices (SCDs) was ordered in 93 (91%) cases and 87 (85%) controls; however, we were unable to accurately document uniform compliance in the use of these devices.

With regard to evaluation of our process measures, we found only 17% of cases and controls combined actually had a VTE risk assessment in their chart, and when it was present, it was often incomplete or was completed inaccurately.

Discussion

The goal of this study was to identify factors (patient characteristics and/or processes of care) that may be contributing to the higher than expected incidence of VTE events at our medical center, despite internal audits suggesting near perfect compliance with SCIP-mandated protocols. We found that in addition to usual risk factors for VTE, an overarching theme of our case cohort was their high complexity of illness. At baseline, these patients had significantly greater rates of stroke, thrombophilia, severe lung disease, infection, and history of VTE than controls. Moreover, the hospital courses of cases were significantly more complex than those of controls, as these patients had more procedures, longer lengths of stay and longer index operations, higher rates of postoperative bed rest exceeding 12 hours, and more prevalent central venous access than controls (Table 2). Several of these risk factors have been found to contribute to VTE development despite compliance with prophylaxis protocols.

Cassidy et al reviewed a cohort of nontrauma general surgery patients who developed VTE despite receiving appropriate prophylaxis and found that both multiple operations and emergency procedures contributed to the failure of VTE prophylaxis.¹¹ Similarly, Wang et al identified several independent risk factors for VTE despite thromboprophylaxis, including central venous access and infection, as well as intensive care unit admission, hospitalization for cranial surgery, and admission from a long-term care facility.¹² While our study did not capture some of these additional factors considered by Wang et al, the presence of risk factors not captured in traditional assessment tools suggests that additional consideration for complex patients is warranted.

In addition to these nonmodifiable patient characteristics, aspects of our VTE prophylaxis processes likely contributed to the higher than expected rate of VTE. While the electronic medical record at our institution does contain a VTE risk assessment tool based on the Caprini score, we found it often is not used at all or is used incorrectly/incompletely, which likely reflects the fact that physicians are neither prompted nor required to complete the assessment prior to prescribing VTE prophylaxis.

There is a significant body of evidence demonstrating that mandatory computerized VTE risk assessments can effectively reduce VTE rates and that improved outcomes occur shortly after implementation. Cassidy et al demonstrated the benefits of instituting a hospital-wide, mandatory, Caprini-based computerized VTE risk assessment that provides prophylaxis/early ambulation recommendations. Two years after implementing this system, they observed an 84% reduction in DVTs (P < 0.001) and a 55% reduction in PEs (P < 0.001).¹³ Nimeri et al had similarly impressive success, achieving a reduction in their NSQIP O/E for PE/DVT in general surgery from 6.00 in 2010 to 0.82 (for DVTs) and 0.78 (for PEs) 5 years after implementation of mandatory VTE risk assessment (though they noted that the most dramatic reduction occurred 1 year after implementation).¹⁴ Additionally, a recent systematic review and meta-analysis by Borab et al found computerized VTE risk assessments to be associated with a significant decrease in VTE events.¹⁵

The risk assessment tool used at our institution is qualitative in nature, and current literature suggests that employing a more quantitative tool may yield improved outcomes. Numerous studies have highlighted the importance of identifying patients at very high risk for VTE, as higher risk may necessitate more careful consideration of their prophylactic regimens. Obi et al found patients with Caprini scores higher than 8 to be at significantly greater risk of developing VTE compared to patients with scores of 7 or 8. Also, patients with scores of 7 or 8 were significantly more likely to have a VTE compared to those with scores of 5 or 6.¹⁶ In another study, Lobastov et al identified Caprini scores of 11 or higher as representing an extremely high-risk category for which standard prophylaxis regimens may not be effective.¹⁷ Thus, while having mandatory risk assessment has been shown to dramatically decrease VTE incidence, it is important to consider the magnitude of the numerical risk score. This is of particular importance at medical centers with high case-mix indices where patients at the highest risk might need to be managed with different prophylactic guidelines.

Another notable aspect of the process at our hospital was the great variation in the types of prophylactic regimens ordered, and the adherence to what was ordered. Only 25.5% of patients were maintained on a standard prophylactic regimen with no missed doses (heparin 5000 every 8 hours or enoxaparin 40 mg daily). Thus, the vast majority of the patients who went on to develop VTE either were prescribed a nontraditional prophylaxis regimen or missed doses of standard agents. The need for secondary surgical procedures or other invasive interventions may explain many, but not all, of the missed doses.

The timing of prophylaxis initiation for our patients was also found to deviate from accepted standards. Only 16.8% of cases received prophylaxis upon induction of anesthesia, and furthermore, 38% of cases did not receive any anticoagulation within 24 hours of their index operation. While this variability in prophylaxis implementation was acceptable within the SCIP guidelines based on “high risk for bleeding” or other considerations, it likely contributed to our suboptimal outcomes. The variations and interruptions in prophylactic regimens speak to barriers that have previously been reported as contributing factors to noncompliance with VTE prophylaxis.¹⁸

Given these known barriers and the observed underutilization and improper use of our risk assessment tool, we have recently changed our surgical admission order sets such that a mandatory quantitative risk assessment must be done for every surgical patient at the time of admission/operation before other orders can be completed. Following completion of the assessment, the physician will be presented with an appropriate standard regimen based on the individual patient’s risk assessment. Early results of our VTE quality improvement project have been satisfying: in the most recent NSQIP semi-annual report, our O/E for VTE was 0.74, placing us in the first decile. Some of these early reports may simply be the product of the Hawthorne effect; however, we are encouraged by the early improvements seen in other research. While we are hopeful that these changes will result in sustainable improvements in outcomes, patients at extremely high risk may require novel weight-based or otherwise customized aggressive prophylactic regimens. Such regimens have already been proposed for arthroplasty and other high-risk patients.

Future research may identify other risk factors not captured by traditional risk assessments. In addition, research should continue to explore the use and efficacy of standard prophylactic regimens in these populations to help determine if they are sufficient. Currently, weight-based low-molecular-weight heparin dosing and alternative regimens employing fondaparinux are under investigation for very-high-risk patients.¹⁹

There were several limitations to the present study. First, due to the retrospective design of our study, we could collect only data that had been uniformly recorded in the charts throughout the study period. Second, we were unable to accurately assess compliance with mechanical prophylaxis. While our chart review showed that the vast majority of cases and controls were ordered to have mechanical prophylaxis, it is impossible to document how often these devices were used appropriately in a retrospective analysis. Anecdotal observation suggests that once patients are out of post-anesthesia or critical care units, SCD use is not standardized. The inability to measure compliance precisely may be leading to an overestimation of our compliance with prophylaxis. Finally, because our study included only patients who underwent surgery at our hospital, our observations may not be generalizable outside our institution.

Conclusion

Our study findings reinforce the importance of attention to detail in VTE risk assessment and in ordering and administering VTE prophylactic regimens, especially in high-risk surgical patients. While we adhered to the SCIP-mandated prophylaxis requirements, the complexity of our patients and our lack of a truly standardized approach to risk assessment and prophylactic regimens resulted in suboptimal outcomes. Stricter and more quantitative mandatory VTE risk assessment, along with highly standardized VTE prophylaxis regimens, are required to achieve optimal outcomes.

Corresponding author: Jason C. DeGiovanni, MS, BA, Jason.DeGiovanni@tufts.edu.

Financial disclosures: None.

From Tufts Medical Center, Boston, MA.

Abstract

• Objective: Audits at our academic medical center revealed near 100% compliance with protocols for perioperative venous thromboembolism (VTE) prophylaxis, but recent National Surgical Quality Improvement Program data demonstrated a higher than expected incidence of VTE (observed/expected = 1.32). The objective of this study was to identify potential causes of this discrepancy.
• Design: Retrospective case-control study.
• Setting: Urban academic medical center with high case-mix indices (Medicare approximately 2.4, non-Medicare approximately 2.0).
• Participants: 102 surgical inpatients with VTE (September 2012 to October 2015) matched with controls for age, gender, and type of procedure.
• Measurements: Prevalence of common VTE risk factors, length of stay, number of procedures, index operation times, and postoperative bed rest > 12 hours were assessed. Utilization of and compliance with our VTE risk assessment tool was also investigated.
• Results: Cases underwent more procedures and had longer lengths of stay and index procedures than controls. In addition, cases were more likely to have had > 12 hours of postoperative bed rest and central venous access than controls. Cases had more infections and were more likely to have severe lung disease, thrombophilia, and a history of prior VTE than controls. No differences in body mass index, tobacco use, current or previous malignancy, or VTE risk assessment form use were observed. Overall, care complexity and risk factors were equally important in determining VTE incidence. Our analyses also revealed lack of strict adherence to our VTE risk stratification protocol and frequent use of suboptimal prophylactic regimens.
• Conclusion: Well-accepted risk factors and overall care complexity determine VTE risk. Preventing VTE in high-risk patients requires assiduous attention to detail in VTE risk assessment and in delivery of optimal prophylaxis. Patients at especially high risk may require customized prophylactic regimens.

Keywords: hospital-acquired venous thromboembolic disease; VTE prophylaxis, surgical patients.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are well-recognized causes of morbidity and mortality in surgical patients. Between 350,000 and 600,000 cases of venous thromboembolism (VTE) occur each year in the United States, and it is responsible for approximately 10% of preventable in-hospital fatalities.^1-3 Given VTE’s impact on patients and the healthcare system and the fact that it is preventable, intense effort has been focused on developing more effective prophylactic measures to decrease its incidence.^2-4 In 2008, the surgeon general issued a “call to action” for increased efforts to prevent VTE.⁵

The American College of Chest Physicians (ACCP) guidelines subcategorize patients based on type of surgery. In addition, the ACCP guidelines support the use of a Caprini-based scoring system to aid in risk stratification and improve clinical decision-making (Table 1).^4,6-9 In general, scores ≥ 5 qualify individuals as high risk. Based on their risk category, patients receive mechanical prophylaxis, chemical prophylaxis, or a combination of the 2. Lower-risk patients who are ambulatory typically receive only mechanical prophylaxis while in bed, whereas higher-risk patients receive a combination of mechanical prophylaxis and chemoprophylaxis measures.⁷ In general, low-molecular-weight heparin (40 mg daily) and low-dose unfractionated heparin (5000 units 3 times daily) have been the standard evidence-based options for chemoprophylaxis in surgical patients. Absolute contraindications for prophylaxis include active bleeding and known increased risk of bleeding based on patient- or procedure-specific factors.

Our hospital, a 350-bed academic medical center in downtown Boston, MA, serving a diverse population with a very high case-mix index (2.4 Medicare and 2.0 non-Medicare), has strict protocols for VTE prophylaxis consistent with the ACCP guidelines and based on the Surgical Care Improvement Project (SCIP) measures published in 2006.¹⁰ The SCIP mandates allow for considerable surgeon discretion in the use of chemoprophylaxis for neurosurgical cases and general and orthopedic surgery cases deemed to be at high risk for bleeding. In addition, SCIP requires only that prophylaxis be initiated within 24 hours of surgical end time. Although recent audits revealed nearly 100% compliance with SCIP-mandated protocols, National Surgical Quality Improvement Program (NSQIP) data showed that the incidence of VTE events at our institution was higher than expected (observed/expected [O/E] = 1.32).

In order to determine the reasons for this mismatch between process and outcome performance, we investigated whether there were characteristics of our patient population that contributed to the higher than expected rates of VTE, and we scrutinized our VTE prophylaxis protocol to determine if there were aspects of our process that were also contributory.

Methods

Study Sample

This is a retrospective case-control study of surgical inpatients at our hospital during the period September 2012 to October 2015. Cases were identified as patients diagnosed with a VTE (DVT or PE). Controls were identified from a pool of surgical patients whose courses were not complicated by VTE during the same time frame as the cases and who were matched as closely as possible by procedure code, age, and gender.

 

 

Variables

Patient and hospital course variables that were analyzed included demographics, comorbidities, length of stay, number of procedures, index operation times, duration of postoperative bed rest, use of mechanical prophylaxis, and type of chemoprophylaxis and time frame within which it was initiated. Data were collected via chart review using International Classification of Diseases-9 and -10 codes to identify surgical cases within the allotted time period who were diagnosed with VTE. Demographic variables included age, sex, and ethnicity. Comorbidities included hypertension, diabetes, coronary artery disease, serious lung disease, previous or current malignancy, documented hypercoagulable state, and previous history of VTE. Body mass index (BMI) was also recorded. The aforementioned disease-specific variables were not matched between the case and control groups, as this data was obtained retrospectively during data collection.

Analysis

Associations between case and matched control were analyzed using the paired t-test for continuous variables and McNemar’s test for categorical variables. P values < 0.05 were considered statistically significant. SAS Enterprise Guide 7.15 (Cary, NC) was used for all statistical analyses.

The requirement for informed consent was waived by our Institutional Review Board, as the study was initially deemed to be a quality improvement project, and all data used for this report were de-identified.

Results

Our retrospective case-control analysis included a sample of 102 surgical patients whose courses were complicated by VTE between September 2012 and October 2015. The cases were distributed among 6 different surgical categories (Figure 1): trauma (20%), cancer (10%), cardiovascular (21%), noncancer neurosurgery (28%), elective orthopedics (11%), and miscellaneous general surgery (10%).

Comparisons between cases and controls in terms of patient demographics and risk factors are shown in Table 2. No statistically significant difference was observed in ethnicity or race between the 2 groups. Overall, cases had more hip/pelvis/leg fractures at presentation (P = 0.0008). The case group also had higher proportions of patients with postoperative bed rest greater than 12 hours (P = 0.009), central venous access (P < 0.0001), infection (P < 0.0001), and lower extremity edema documented during the hospitalization prior to development of DVT (P < 0.0001). Additionally, cases had significantly greater rates of previous VTE (P = 0.0004), inherited or acquired thrombophilia (P = 0.03), history of stroke (P = 0.0003), and severe lung disease, including pneumonia (P = 0.0008). No significant differences were noted between cases and matched controls in BMI (P = 0.43), current tobacco use (P = 0.71), current malignancy (P = 0.80), previous malignancy (P = 0.83), head trauma (P = 0.17), or acute cardiac disease (myocardial infarction or congestive heart failure; P = 0.12).

Variables felt to indicate overall complexity of hospital course for cases as compared to controls are outlined in Table 3. Cases were found to have significantly longer lengths of stay (median, 15.5 days versus 3 days, P < 0.0001). To account for the possibility that the development of VTE contributed to the increased length of stay in the cases, we also looked at the duration between admission date and the date of VTE diagnosis and determined that cases still had a longer length of stay when this was accounted for (median, 7 days versus 3 days, P < 0.0001). A much higher proportion of cases underwent more than 1 procedure compared to controls (P < 0.0001), and cases had significantly longer index operations as compared to controls (P = 0.002).

Seventeen cases received heparin on induction during their index procedure, compared to 23 controls (P = 0.24). Additionally, 63 cases began a prophylaxis regimen within 24 hours of surgery end time, compared to 68 controls (P = 0.24). The chemoprophylactic regimens utilized in cases and in controls are summarized in Figure 2. Of note, only 26 cases and 32 controls received standard prophylactic regimens with no missed doses (heparin 5000 units 3 times daily or enoxaparin 40 mg daily). Additionally, in over half of cases and a third of controls, nonstandard regimens were ordered. Examples of nonstandard regimens included nonstandard heparin or enoxaparin doses, low-dose warfarin, or aspirin alone. In most cases, nonstandard regimens were justified on the basis of high risk for bleeding.

Mechanical prophylaxis with pneumatic sequential compression devices (SCDs) was ordered in 93 (91%) cases and 87 (85%) controls; however, we were unable to accurately document uniform compliance in the use of these devices.

With regard to evaluation of our process measures, we found only 17% of cases and controls combined actually had a VTE risk assessment in their chart, and when it was present, it was often incomplete or was completed inaccurately.

Discussion

The goal of this study was to identify factors (patient characteristics and/or processes of care) that may be contributing to the higher than expected incidence of VTE events at our medical center, despite internal audits suggesting near perfect compliance with SCIP-mandated protocols. We found that in addition to usual risk factors for VTE, an overarching theme of our case cohort was their high complexity of illness. At baseline, these patients had significantly greater rates of stroke, thrombophilia, severe lung disease, infection, and history of VTE than controls. Moreover, the hospital courses of cases were significantly more complex than those of controls, as these patients had more procedures, longer lengths of stay and longer index operations, higher rates of postoperative bed rest exceeding 12 hours, and more prevalent central venous access than controls (Table 2). Several of these risk factors have been found to contribute to VTE development despite compliance with prophylaxis protocols.

Cassidy et al reviewed a cohort of nontrauma general surgery patients who developed VTE despite receiving appropriate prophylaxis and found that both multiple operations and emergency procedures contributed to the failure of VTE prophylaxis.¹¹ Similarly, Wang et al identified several independent risk factors for VTE despite thromboprophylaxis, including central venous access and infection, as well as intensive care unit admission, hospitalization for cranial surgery, and admission from a long-term care facility.¹² While our study did not capture some of these additional factors considered by Wang et al, the presence of risk factors not captured in traditional assessment tools suggests that additional consideration for complex patients is warranted.

In addition to these nonmodifiable patient characteristics, aspects of our VTE prophylaxis processes likely contributed to the higher than expected rate of VTE. While the electronic medical record at our institution does contain a VTE risk assessment tool based on the Caprini score, we found it often is not used at all or is used incorrectly/incompletely, which likely reflects the fact that physicians are neither prompted nor required to complete the assessment prior to prescribing VTE prophylaxis.

There is a significant body of evidence demonstrating that mandatory computerized VTE risk assessments can effectively reduce VTE rates and that improved outcomes occur shortly after implementation. Cassidy et al demonstrated the benefits of instituting a hospital-wide, mandatory, Caprini-based computerized VTE risk assessment that provides prophylaxis/early ambulation recommendations. Two years after implementing this system, they observed an 84% reduction in DVTs (P < 0.001) and a 55% reduction in PEs (P < 0.001).¹³ Nimeri et al had similarly impressive success, achieving a reduction in their NSQIP O/E for PE/DVT in general surgery from 6.00 in 2010 to 0.82 (for DVTs) and 0.78 (for PEs) 5 years after implementation of mandatory VTE risk assessment (though they noted that the most dramatic reduction occurred 1 year after implementation).¹⁴ Additionally, a recent systematic review and meta-analysis by Borab et al found computerized VTE risk assessments to be associated with a significant decrease in VTE events.¹⁵

The risk assessment tool used at our institution is qualitative in nature, and current literature suggests that employing a more quantitative tool may yield improved outcomes. Numerous studies have highlighted the importance of identifying patients at very high risk for VTE, as higher risk may necessitate more careful consideration of their prophylactic regimens. Obi et al found patients with Caprini scores higher than 8 to be at significantly greater risk of developing VTE compared to patients with scores of 7 or 8. Also, patients with scores of 7 or 8 were significantly more likely to have a VTE compared to those with scores of 5 or 6.¹⁶ In another study, Lobastov et al identified Caprini scores of 11 or higher as representing an extremely high-risk category for which standard prophylaxis regimens may not be effective.¹⁷ Thus, while having mandatory risk assessment has been shown to dramatically decrease VTE incidence, it is important to consider the magnitude of the numerical risk score. This is of particular importance at medical centers with high case-mix indices where patients at the highest risk might need to be managed with different prophylactic guidelines.

Another notable aspect of the process at our hospital was the great variation in the types of prophylactic regimens ordered, and the adherence to what was ordered. Only 25.5% of patients were maintained on a standard prophylactic regimen with no missed doses (heparin 5000 every 8 hours or enoxaparin 40 mg daily). Thus, the vast majority of the patients who went on to develop VTE either were prescribed a nontraditional prophylaxis regimen or missed doses of standard agents. The need for secondary surgical procedures or other invasive interventions may explain many, but not all, of the missed doses.

The timing of prophylaxis initiation for our patients was also found to deviate from accepted standards. Only 16.8% of cases received prophylaxis upon induction of anesthesia, and furthermore, 38% of cases did not receive any anticoagulation within 24 hours of their index operation. While this variability in prophylaxis implementation was acceptable within the SCIP guidelines based on “high risk for bleeding” or other considerations, it likely contributed to our suboptimal outcomes. The variations and interruptions in prophylactic regimens speak to barriers that have previously been reported as contributing factors to noncompliance with VTE prophylaxis.¹⁸

Given these known barriers and the observed underutilization and improper use of our risk assessment tool, we have recently changed our surgical admission order sets such that a mandatory quantitative risk assessment must be done for every surgical patient at the time of admission/operation before other orders can be completed. Following completion of the assessment, the physician will be presented with an appropriate standard regimen based on the individual patient’s risk assessment. Early results of our VTE quality improvement project have been satisfying: in the most recent NSQIP semi-annual report, our O/E for VTE was 0.74, placing us in the first decile. Some of these early reports may simply be the product of the Hawthorne effect; however, we are encouraged by the early improvements seen in other research. While we are hopeful that these changes will result in sustainable improvements in outcomes, patients at extremely high risk may require novel weight-based or otherwise customized aggressive prophylactic regimens. Such regimens have already been proposed for arthroplasty and other high-risk patients.

Future research may identify other risk factors not captured by traditional risk assessments. In addition, research should continue to explore the use and efficacy of standard prophylactic regimens in these populations to help determine if they are sufficient. Currently, weight-based low-molecular-weight heparin dosing and alternative regimens employing fondaparinux are under investigation for very-high-risk patients.¹⁹

There were several limitations to the present study. First, due to the retrospective design of our study, we could collect only data that had been uniformly recorded in the charts throughout the study period. Second, we were unable to accurately assess compliance with mechanical prophylaxis. While our chart review showed that the vast majority of cases and controls were ordered to have mechanical prophylaxis, it is impossible to document how often these devices were used appropriately in a retrospective analysis. Anecdotal observation suggests that once patients are out of post-anesthesia or critical care units, SCD use is not standardized. The inability to measure compliance precisely may be leading to an overestimation of our compliance with prophylaxis. Finally, because our study included only patients who underwent surgery at our hospital, our observations may not be generalizable outside our institution.

Conclusion

Our study findings reinforce the importance of attention to detail in VTE risk assessment and in ordering and administering VTE prophylactic regimens, especially in high-risk surgical patients. While we adhered to the SCIP-mandated prophylaxis requirements, the complexity of our patients and our lack of a truly standardized approach to risk assessment and prophylactic regimens resulted in suboptimal outcomes. Stricter and more quantitative mandatory VTE risk assessment, along with highly standardized VTE prophylaxis regimens, are required to achieve optimal outcomes.

Corresponding author: Jason C. DeGiovanni, MS, BA, Jason.DeGiovanni@tufts.edu.

Financial disclosures: None.

From Tufts Medical Center, Boston, MA.

Abstract

• Objective: Audits at our academic medical center revealed near 100% compliance with protocols for perioperative venous thromboembolism (VTE) prophylaxis, but recent National Surgical Quality Improvement Program data demonstrated a higher than expected incidence of VTE (observed/expected = 1.32). The objective of this study was to identify potential causes of this discrepancy.
• Design: Retrospective case-control study.
• Setting: Urban academic medical center with high case-mix indices (Medicare approximately 2.4, non-Medicare approximately 2.0).
• Participants: 102 surgical inpatients with VTE (September 2012 to October 2015) matched with controls for age, gender, and type of procedure.
• Measurements: Prevalence of common VTE risk factors, length of stay, number of procedures, index operation times, and postoperative bed rest > 12 hours were assessed. Utilization of and compliance with our VTE risk assessment tool was also investigated.
• Results: Cases underwent more procedures and had longer lengths of stay and index procedures than controls. In addition, cases were more likely to have had > 12 hours of postoperative bed rest and central venous access than controls. Cases had more infections and were more likely to have severe lung disease, thrombophilia, and a history of prior VTE than controls. No differences in body mass index, tobacco use, current or previous malignancy, or VTE risk assessment form use were observed. Overall, care complexity and risk factors were equally important in determining VTE incidence. Our analyses also revealed lack of strict adherence to our VTE risk stratification protocol and frequent use of suboptimal prophylactic regimens.
• Conclusion: Well-accepted risk factors and overall care complexity determine VTE risk. Preventing VTE in high-risk patients requires assiduous attention to detail in VTE risk assessment and in delivery of optimal prophylaxis. Patients at especially high risk may require customized prophylactic regimens.

Keywords: hospital-acquired venous thromboembolic disease; VTE prophylaxis, surgical patients.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are well-recognized causes of morbidity and mortality in surgical patients. Between 350,000 and 600,000 cases of venous thromboembolism (VTE) occur each year in the United States, and it is responsible for approximately 10% of preventable in-hospital fatalities.^1-3 Given VTE’s impact on patients and the healthcare system and the fact that it is preventable, intense effort has been focused on developing more effective prophylactic measures to decrease its incidence.^2-4 In 2008, the surgeon general issued a “call to action” for increased efforts to prevent VTE.⁵

The American College of Chest Physicians (ACCP) guidelines subcategorize patients based on type of surgery. In addition, the ACCP guidelines support the use of a Caprini-based scoring system to aid in risk stratification and improve clinical decision-making (Table 1).^4,6-9 In general, scores ≥ 5 qualify individuals as high risk. Based on their risk category, patients receive mechanical prophylaxis, chemical prophylaxis, or a combination of the 2. Lower-risk patients who are ambulatory typically receive only mechanical prophylaxis while in bed, whereas higher-risk patients receive a combination of mechanical prophylaxis and chemoprophylaxis measures.⁷ In general, low-molecular-weight heparin (40 mg daily) and low-dose unfractionated heparin (5000 units 3 times daily) have been the standard evidence-based options for chemoprophylaxis in surgical patients. Absolute contraindications for prophylaxis include active bleeding and known increased risk of bleeding based on patient- or procedure-specific factors.

Our hospital, a 350-bed academic medical center in downtown Boston, MA, serving a diverse population with a very high case-mix index (2.4 Medicare and 2.0 non-Medicare), has strict protocols for VTE prophylaxis consistent with the ACCP guidelines and based on the Surgical Care Improvement Project (SCIP) measures published in 2006.¹⁰ The SCIP mandates allow for considerable surgeon discretion in the use of chemoprophylaxis for neurosurgical cases and general and orthopedic surgery cases deemed to be at high risk for bleeding. In addition, SCIP requires only that prophylaxis be initiated within 24 hours of surgical end time. Although recent audits revealed nearly 100% compliance with SCIP-mandated protocols, National Surgical Quality Improvement Program (NSQIP) data showed that the incidence of VTE events at our institution was higher than expected (observed/expected [O/E] = 1.32).

In order to determine the reasons for this mismatch between process and outcome performance, we investigated whether there were characteristics of our patient population that contributed to the higher than expected rates of VTE, and we scrutinized our VTE prophylaxis protocol to determine if there were aspects of our process that were also contributory.

Methods

Study Sample

This is a retrospective case-control study of surgical inpatients at our hospital during the period September 2012 to October 2015. Cases were identified as patients diagnosed with a VTE (DVT or PE). Controls were identified from a pool of surgical patients whose courses were not complicated by VTE during the same time frame as the cases and who were matched as closely as possible by procedure code, age, and gender.

 

 

Variables

Patient and hospital course variables that were analyzed included demographics, comorbidities, length of stay, number of procedures, index operation times, duration of postoperative bed rest, use of mechanical prophylaxis, and type of chemoprophylaxis and time frame within which it was initiated. Data were collected via chart review using International Classification of Diseases-9 and -10 codes to identify surgical cases within the allotted time period who were diagnosed with VTE. Demographic variables included age, sex, and ethnicity. Comorbidities included hypertension, diabetes, coronary artery disease, serious lung disease, previous or current malignancy, documented hypercoagulable state, and previous history of VTE. Body mass index (BMI) was also recorded. The aforementioned disease-specific variables were not matched between the case and control groups, as this data was obtained retrospectively during data collection.

Analysis

Associations between case and matched control were analyzed using the paired t-test for continuous variables and McNemar’s test for categorical variables. P values < 0.05 were considered statistically significant. SAS Enterprise Guide 7.15 (Cary, NC) was used for all statistical analyses.

The requirement for informed consent was waived by our Institutional Review Board, as the study was initially deemed to be a quality improvement project, and all data used for this report were de-identified.

Results

Our retrospective case-control analysis included a sample of 102 surgical patients whose courses were complicated by VTE between September 2012 and October 2015. The cases were distributed among 6 different surgical categories (Figure 1): trauma (20%), cancer (10%), cardiovascular (21%), noncancer neurosurgery (28%), elective orthopedics (11%), and miscellaneous general surgery (10%).

Comparisons between cases and controls in terms of patient demographics and risk factors are shown in Table 2. No statistically significant difference was observed in ethnicity or race between the 2 groups. Overall, cases had more hip/pelvis/leg fractures at presentation (P = 0.0008). The case group also had higher proportions of patients with postoperative bed rest greater than 12 hours (P = 0.009), central venous access (P < 0.0001), infection (P < 0.0001), and lower extremity edema documented during the hospitalization prior to development of DVT (P < 0.0001). Additionally, cases had significantly greater rates of previous VTE (P = 0.0004), inherited or acquired thrombophilia (P = 0.03), history of stroke (P = 0.0003), and severe lung disease, including pneumonia (P = 0.0008). No significant differences were noted between cases and matched controls in BMI (P = 0.43), current tobacco use (P = 0.71), current malignancy (P = 0.80), previous malignancy (P = 0.83), head trauma (P = 0.17), or acute cardiac disease (myocardial infarction or congestive heart failure; P = 0.12).

Variables felt to indicate overall complexity of hospital course for cases as compared to controls are outlined in Table 3. Cases were found to have significantly longer lengths of stay (median, 15.5 days versus 3 days, P < 0.0001). To account for the possibility that the development of VTE contributed to the increased length of stay in the cases, we also looked at the duration between admission date and the date of VTE diagnosis and determined that cases still had a longer length of stay when this was accounted for (median, 7 days versus 3 days, P < 0.0001). A much higher proportion of cases underwent more than 1 procedure compared to controls (P < 0.0001), and cases had significantly longer index operations as compared to controls (P = 0.002).

Seventeen cases received heparin on induction during their index procedure, compared to 23 controls (P = 0.24). Additionally, 63 cases began a prophylaxis regimen within 24 hours of surgery end time, compared to 68 controls (P = 0.24). The chemoprophylactic regimens utilized in cases and in controls are summarized in Figure 2. Of note, only 26 cases and 32 controls received standard prophylactic regimens with no missed doses (heparin 5000 units 3 times daily or enoxaparin 40 mg daily). Additionally, in over half of cases and a third of controls, nonstandard regimens were ordered. Examples of nonstandard regimens included nonstandard heparin or enoxaparin doses, low-dose warfarin, or aspirin alone. In most cases, nonstandard regimens were justified on the basis of high risk for bleeding.

Mechanical prophylaxis with pneumatic sequential compression devices (SCDs) was ordered in 93 (91%) cases and 87 (85%) controls; however, we were unable to accurately document uniform compliance in the use of these devices.

With regard to evaluation of our process measures, we found only 17% of cases and controls combined actually had a VTE risk assessment in their chart, and when it was present, it was often incomplete or was completed inaccurately.

Discussion

The goal of this study was to identify factors (patient characteristics and/or processes of care) that may be contributing to the higher than expected incidence of VTE events at our medical center, despite internal audits suggesting near perfect compliance with SCIP-mandated protocols. We found that in addition to usual risk factors for VTE, an overarching theme of our case cohort was their high complexity of illness. At baseline, these patients had significantly greater rates of stroke, thrombophilia, severe lung disease, infection, and history of VTE than controls. Moreover, the hospital courses of cases were significantly more complex than those of controls, as these patients had more procedures, longer lengths of stay and longer index operations, higher rates of postoperative bed rest exceeding 12 hours, and more prevalent central venous access than controls (Table 2). Several of these risk factors have been found to contribute to VTE development despite compliance with prophylaxis protocols.

Cassidy et al reviewed a cohort of nontrauma general surgery patients who developed VTE despite receiving appropriate prophylaxis and found that both multiple operations and emergency procedures contributed to the failure of VTE prophylaxis.¹¹ Similarly, Wang et al identified several independent risk factors for VTE despite thromboprophylaxis, including central venous access and infection, as well as intensive care unit admission, hospitalization for cranial surgery, and admission from a long-term care facility.¹² While our study did not capture some of these additional factors considered by Wang et al, the presence of risk factors not captured in traditional assessment tools suggests that additional consideration for complex patients is warranted.

In addition to these nonmodifiable patient characteristics, aspects of our VTE prophylaxis processes likely contributed to the higher than expected rate of VTE. While the electronic medical record at our institution does contain a VTE risk assessment tool based on the Caprini score, we found it often is not used at all or is used incorrectly/incompletely, which likely reflects the fact that physicians are neither prompted nor required to complete the assessment prior to prescribing VTE prophylaxis.

There is a significant body of evidence demonstrating that mandatory computerized VTE risk assessments can effectively reduce VTE rates and that improved outcomes occur shortly after implementation. Cassidy et al demonstrated the benefits of instituting a hospital-wide, mandatory, Caprini-based computerized VTE risk assessment that provides prophylaxis/early ambulation recommendations. Two years after implementing this system, they observed an 84% reduction in DVTs (P < 0.001) and a 55% reduction in PEs (P < 0.001).¹³ Nimeri et al had similarly impressive success, achieving a reduction in their NSQIP O/E for PE/DVT in general surgery from 6.00 in 2010 to 0.82 (for DVTs) and 0.78 (for PEs) 5 years after implementation of mandatory VTE risk assessment (though they noted that the most dramatic reduction occurred 1 year after implementation).¹⁴ Additionally, a recent systematic review and meta-analysis by Borab et al found computerized VTE risk assessments to be associated with a significant decrease in VTE events.¹⁵

The risk assessment tool used at our institution is qualitative in nature, and current literature suggests that employing a more quantitative tool may yield improved outcomes. Numerous studies have highlighted the importance of identifying patients at very high risk for VTE, as higher risk may necessitate more careful consideration of their prophylactic regimens. Obi et al found patients with Caprini scores higher than 8 to be at significantly greater risk of developing VTE compared to patients with scores of 7 or 8. Also, patients with scores of 7 or 8 were significantly more likely to have a VTE compared to those with scores of 5 or 6.¹⁶ In another study, Lobastov et al identified Caprini scores of 11 or higher as representing an extremely high-risk category for which standard prophylaxis regimens may not be effective.¹⁷ Thus, while having mandatory risk assessment has been shown to dramatically decrease VTE incidence, it is important to consider the magnitude of the numerical risk score. This is of particular importance at medical centers with high case-mix indices where patients at the highest risk might need to be managed with different prophylactic guidelines.

Another notable aspect of the process at our hospital was the great variation in the types of prophylactic regimens ordered, and the adherence to what was ordered. Only 25.5% of patients were maintained on a standard prophylactic regimen with no missed doses (heparin 5000 every 8 hours or enoxaparin 40 mg daily). Thus, the vast majority of the patients who went on to develop VTE either were prescribed a nontraditional prophylaxis regimen or missed doses of standard agents. The need for secondary surgical procedures or other invasive interventions may explain many, but not all, of the missed doses.

The timing of prophylaxis initiation for our patients was also found to deviate from accepted standards. Only 16.8% of cases received prophylaxis upon induction of anesthesia, and furthermore, 38% of cases did not receive any anticoagulation within 24 hours of their index operation. While this variability in prophylaxis implementation was acceptable within the SCIP guidelines based on “high risk for bleeding” or other considerations, it likely contributed to our suboptimal outcomes. The variations and interruptions in prophylactic regimens speak to barriers that have previously been reported as contributing factors to noncompliance with VTE prophylaxis.¹⁸

Given these known barriers and the observed underutilization and improper use of our risk assessment tool, we have recently changed our surgical admission order sets such that a mandatory quantitative risk assessment must be done for every surgical patient at the time of admission/operation before other orders can be completed. Following completion of the assessment, the physician will be presented with an appropriate standard regimen based on the individual patient’s risk assessment. Early results of our VTE quality improvement project have been satisfying: in the most recent NSQIP semi-annual report, our O/E for VTE was 0.74, placing us in the first decile. Some of these early reports may simply be the product of the Hawthorne effect; however, we are encouraged by the early improvements seen in other research. While we are hopeful that these changes will result in sustainable improvements in outcomes, patients at extremely high risk may require novel weight-based or otherwise customized aggressive prophylactic regimens. Such regimens have already been proposed for arthroplasty and other high-risk patients.

Future research may identify other risk factors not captured by traditional risk assessments. In addition, research should continue to explore the use and efficacy of standard prophylactic regimens in these populations to help determine if they are sufficient. Currently, weight-based low-molecular-weight heparin dosing and alternative regimens employing fondaparinux are under investigation for very-high-risk patients.¹⁹

There were several limitations to the present study. First, due to the retrospective design of our study, we could collect only data that had been uniformly recorded in the charts throughout the study period. Second, we were unable to accurately assess compliance with mechanical prophylaxis. While our chart review showed that the vast majority of cases and controls were ordered to have mechanical prophylaxis, it is impossible to document how often these devices were used appropriately in a retrospective analysis. Anecdotal observation suggests that once patients are out of post-anesthesia or critical care units, SCD use is not standardized. The inability to measure compliance precisely may be leading to an overestimation of our compliance with prophylaxis. Finally, because our study included only patients who underwent surgery at our hospital, our observations may not be generalizable outside our institution.

Conclusion

Our study findings reinforce the importance of attention to detail in VTE risk assessment and in ordering and administering VTE prophylactic regimens, especially in high-risk surgical patients. While we adhered to the SCIP-mandated prophylaxis requirements, the complexity of our patients and our lack of a truly standardized approach to risk assessment and prophylactic regimens resulted in suboptimal outcomes. Stricter and more quantitative mandatory VTE risk assessment, along with highly standardized VTE prophylaxis regimens, are required to achieve optimal outcomes.

Corresponding author: Jason C. DeGiovanni, MS, BA, Jason.DeGiovanni@tufts.edu.

Financial disclosures: None.