Pulmonary Health Hub

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

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, [email protected].

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, [email protected].

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, [email protected].

Financial disclosures: None.

Oral immunotherapy reduced sensitivity to peanuts in allergic individuals, but at the cost of increased risk of anaphylaxis and other reactions, based on a meta-analysis from more than 1,000 patients published in the Lancet.

copyright mates/Fotolia.com

In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).

Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).

In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).

Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.

The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.

The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.

However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.

The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.

Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.

SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.

Oral immunotherapy reduced sensitivity to peanuts in allergic individuals, but at the cost of increased risk of anaphylaxis and other reactions, based on a meta-analysis from more than 1,000 patients published in the Lancet.

copyright mates/Fotolia.com

In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).

Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).

In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).

Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.

The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.

The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.

However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.

The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.

Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.

SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.

Oral immunotherapy reduced sensitivity to peanuts in allergic individuals, but at the cost of increased risk of anaphylaxis and other reactions, based on a meta-analysis from more than 1,000 patients published in the Lancet.

copyright mates/Fotolia.com

In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).

Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).

In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).

Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.

The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.

The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.

However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.

The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.

Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.

SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

[email protected]

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

[email protected]

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

[email protected]

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

[email protected]

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

[email protected]

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

[email protected]

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

[email protected]

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

[email protected]

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

[email protected]

LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.

He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.

The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.

“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.

There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.

Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.

The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.

“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.

The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.

The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.

Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.

Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.

Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.

[email protected]
 

LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.

He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.

The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.

“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.

There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.

Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.

The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.

“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.

The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.

The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.

Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.

Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.

Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.

[email protected]
 

LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.

He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.

The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.

“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.

There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.

Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.

The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.

“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.

The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.

The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.

Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.

Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.

Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.

[email protected]