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Surgical infections, early discharge hike readmissions in extrahepatic cholangiocarcinoma
WASHINGTON – Hospital readmissions are common after resection of extrahepatic cholangiocarcinoma, with about 20% of patients returning in the first 90 days after surgery.
Two factors – surgical site infections and an abbreviated length of stay – both quadrupled the risk of readmission, Michail Mavros, MD, said at the American College of Surgeons Clinical Congress.
“Surgeons are scrutinized over length of stay and, as a result, these fast-track recovery pathways are increasingly important. Readmission rates are being used as a quality metric and performance indicator, and tied to reimbursement. But our data suggest that we should be somewhat cautious in implementing those with this surgery. The patient may look great with good pain control, and be eating and ambulating by day 4 or 5, but it may be premature to discharge at that point, and safer to wait a little longer. The financial penalty for readmission is probably not worth that small bonus we get for early discharge.”
The study comprised 422 patients who underwent resection with curative intent for extrahepatic cholangiocarcinoma. This is a rare tumor with about 5,000 cases presenting each year. Dr. Mavros and his colleagues extracted their data from the U.S. Extrahepatic Cholangiocarcinoma Collaborative. The primary outcomes were 30- and 90-day readmission rates.
The patients’ median age was 67 years. About a third had mild comorbidities with an American Society of Anesthesiologist (ASA) comorbidity class of 1-2. The rest had moderate to severe comorbidities (ASA class 3-4). Hypertension was common (48%); 18% had diabetes.
Tumor location was split almost equally between distal and hilar; the median tumor size was 2.3 cm.
Final margins were positive in 28% and half of the cohort had positive regional lymph nodes.
The procedures were quite varied, and included common bile duct resection (18%); hepatectomy plus common bile duct resection (40%); and Whipple procedure (42%). The median estimated blood loss was 500 cc; 28% of the cohort required transfusion with packed red blood cells and 8% with fresh frozen plasma.
Postoperative complications were common (63%), with half of those being classed as serious. Infectious complications were most common, including superficial (11%), deep (7%), and organ space infections (16%).
Bile leaks occurred in 4% of cases. Reoperations were necessary in 7%. The 30-day mortality was 4.5% and 90-day mortality, 8%.The median length of stay was 8 days but this ranged from 7 to 18 days.
The 30-day readmission rate was 19% and the 90-day readmission rate was 23%. Most readmissions occurred fairly quickly – the median time to readmission was 12 days, with a range of 6-24 days.
The investigators conducted a multivariate analysis to determine independent predictors of readmission. The strongest predictors were any surgical complications (odds ratio, 8.4); organ-space infection (OR, 4.5); and length of stay of 8 days or less (OR, 4.3). Other predictors were advancing age (OR, 1.5 for each 10 years) and having had a liver resection (OR, 2.0).
“It’s clear from these results that avoidance of complications, especially infectious complications, may improve readmission rates dramatically,” Dr. Mavros said. “We would advise caution in implementing any fast-track protocols with these patients, given the finding that early discharge was associated with a higher rate of readmission.”
Dr. Mavros had no financial disclosures.
[email protected]
On Twitter @alz_gal
WASHINGTON – Hospital readmissions are common after resection of extrahepatic cholangiocarcinoma, with about 20% of patients returning in the first 90 days after surgery.
Two factors – surgical site infections and an abbreviated length of stay – both quadrupled the risk of readmission, Michail Mavros, MD, said at the American College of Surgeons Clinical Congress.
“Surgeons are scrutinized over length of stay and, as a result, these fast-track recovery pathways are increasingly important. Readmission rates are being used as a quality metric and performance indicator, and tied to reimbursement. But our data suggest that we should be somewhat cautious in implementing those with this surgery. The patient may look great with good pain control, and be eating and ambulating by day 4 or 5, but it may be premature to discharge at that point, and safer to wait a little longer. The financial penalty for readmission is probably not worth that small bonus we get for early discharge.”
The study comprised 422 patients who underwent resection with curative intent for extrahepatic cholangiocarcinoma. This is a rare tumor with about 5,000 cases presenting each year. Dr. Mavros and his colleagues extracted their data from the U.S. Extrahepatic Cholangiocarcinoma Collaborative. The primary outcomes were 30- and 90-day readmission rates.
The patients’ median age was 67 years. About a third had mild comorbidities with an American Society of Anesthesiologist (ASA) comorbidity class of 1-2. The rest had moderate to severe comorbidities (ASA class 3-4). Hypertension was common (48%); 18% had diabetes.
Tumor location was split almost equally between distal and hilar; the median tumor size was 2.3 cm.
Final margins were positive in 28% and half of the cohort had positive regional lymph nodes.
The procedures were quite varied, and included common bile duct resection (18%); hepatectomy plus common bile duct resection (40%); and Whipple procedure (42%). The median estimated blood loss was 500 cc; 28% of the cohort required transfusion with packed red blood cells and 8% with fresh frozen plasma.
Postoperative complications were common (63%), with half of those being classed as serious. Infectious complications were most common, including superficial (11%), deep (7%), and organ space infections (16%).
Bile leaks occurred in 4% of cases. Reoperations were necessary in 7%. The 30-day mortality was 4.5% and 90-day mortality, 8%.The median length of stay was 8 days but this ranged from 7 to 18 days.
The 30-day readmission rate was 19% and the 90-day readmission rate was 23%. Most readmissions occurred fairly quickly – the median time to readmission was 12 days, with a range of 6-24 days.
The investigators conducted a multivariate analysis to determine independent predictors of readmission. The strongest predictors were any surgical complications (odds ratio, 8.4); organ-space infection (OR, 4.5); and length of stay of 8 days or less (OR, 4.3). Other predictors were advancing age (OR, 1.5 for each 10 years) and having had a liver resection (OR, 2.0).
“It’s clear from these results that avoidance of complications, especially infectious complications, may improve readmission rates dramatically,” Dr. Mavros said. “We would advise caution in implementing any fast-track protocols with these patients, given the finding that early discharge was associated with a higher rate of readmission.”
Dr. Mavros had no financial disclosures.
[email protected]
On Twitter @alz_gal
WASHINGTON – Hospital readmissions are common after resection of extrahepatic cholangiocarcinoma, with about 20% of patients returning in the first 90 days after surgery.
Two factors – surgical site infections and an abbreviated length of stay – both quadrupled the risk of readmission, Michail Mavros, MD, said at the American College of Surgeons Clinical Congress.
“Surgeons are scrutinized over length of stay and, as a result, these fast-track recovery pathways are increasingly important. Readmission rates are being used as a quality metric and performance indicator, and tied to reimbursement. But our data suggest that we should be somewhat cautious in implementing those with this surgery. The patient may look great with good pain control, and be eating and ambulating by day 4 or 5, but it may be premature to discharge at that point, and safer to wait a little longer. The financial penalty for readmission is probably not worth that small bonus we get for early discharge.”
The study comprised 422 patients who underwent resection with curative intent for extrahepatic cholangiocarcinoma. This is a rare tumor with about 5,000 cases presenting each year. Dr. Mavros and his colleagues extracted their data from the U.S. Extrahepatic Cholangiocarcinoma Collaborative. The primary outcomes were 30- and 90-day readmission rates.
The patients’ median age was 67 years. About a third had mild comorbidities with an American Society of Anesthesiologist (ASA) comorbidity class of 1-2. The rest had moderate to severe comorbidities (ASA class 3-4). Hypertension was common (48%); 18% had diabetes.
Tumor location was split almost equally between distal and hilar; the median tumor size was 2.3 cm.
Final margins were positive in 28% and half of the cohort had positive regional lymph nodes.
The procedures were quite varied, and included common bile duct resection (18%); hepatectomy plus common bile duct resection (40%); and Whipple procedure (42%). The median estimated blood loss was 500 cc; 28% of the cohort required transfusion with packed red blood cells and 8% with fresh frozen plasma.
Postoperative complications were common (63%), with half of those being classed as serious. Infectious complications were most common, including superficial (11%), deep (7%), and organ space infections (16%).
Bile leaks occurred in 4% of cases. Reoperations were necessary in 7%. The 30-day mortality was 4.5% and 90-day mortality, 8%.The median length of stay was 8 days but this ranged from 7 to 18 days.
The 30-day readmission rate was 19% and the 90-day readmission rate was 23%. Most readmissions occurred fairly quickly – the median time to readmission was 12 days, with a range of 6-24 days.
The investigators conducted a multivariate analysis to determine independent predictors of readmission. The strongest predictors were any surgical complications (odds ratio, 8.4); organ-space infection (OR, 4.5); and length of stay of 8 days or less (OR, 4.3). Other predictors were advancing age (OR, 1.5 for each 10 years) and having had a liver resection (OR, 2.0).
“It’s clear from these results that avoidance of complications, especially infectious complications, may improve readmission rates dramatically,” Dr. Mavros said. “We would advise caution in implementing any fast-track protocols with these patients, given the finding that early discharge was associated with a higher rate of readmission.”
Dr. Mavros had no financial disclosures.
[email protected]
On Twitter @alz_gal
Key clinical point:
Major finding: Organ space infections and a shorter length of stay both quadrupled the risk of a readmission.
Data source: The database review comprised 422 patients.
Disclosures: Dr. Mavros had no financial disclosures.
VA Treats Patients’ Impatience With Clinical Pharmacists
MADISON, WIS.— Something astonishing has happened in the past year to outpatient treatment at the Veterans Affairs hospital here.
Vets regularly get next-day and even same-day appointments for primary care now, no longer waiting a month or more to see a doctor as many once did.
The reason is they don’t all see doctors. Clinical pharmacists — whose special training permits them to prescribe drugs, order lab tests, make referrals to specialists and do physical examinations — are handling more patients’ chronic care needs. That frees physicians to concentrate on new patients and others with complex needs.
A quarter of primary care appointments at the Madison hospital are now handled by clinical pharmacists since they were integrated in patient care teams in 2015. Several VA hospitals — in El Paso, Texas, and Kansas City, Mo., among them — have followed Madison’s approach and more than 36 others are considering it, according to hospital officials.
“It’s made a tremendous positive impact in improving access,” said Dr. Jean Montgomery, chief of primary care services at the Madison hospital.
That’s critical for the VA, the focus of a national scandal in 2014 after news reports revealed the Phoenix VA hospital had booked primary care appointments months in advance, schedulers falsified wait times to make them look shorter and dozens had died awaiting care. Further investigations uncovered similar problems at other VA facilities. More than two years later, tens of thousands of vets are still waiting a month or two for an appointment, according to the latest data from the VA.
The Obama administration has allowed some veterans to seek care in the private sector if they choose, but VA wait times remain long and more action is needed, theGeneral Accountability Office reported in April.
Expanding clinical pharmacists’ role is a solution.
They receive two more years of education than regular pharmacists and they can handle many primary care needs for patients, particularly after physicians have diagnosed their conditions.
The VA has had them for more than 20 years, but their growing involvement in patient care is more recent. This year it employs 3,185 clinical pharmacists with authority to prescribe medications, order lab tests and perform physical assessments — nearly a 50 percent increase since 2011.
“It’s having a significant impact on reducing wait times and our office is trying to expand more of them nationally to increase access,” said Heather Ourth, national clinical program manager for VA Pharmacy Benefits Management Services.
In 2015, VA clinical pharmacists wrote 1.9 million prescriptions for chronic diseases, according to a report co-authored by Ourth and published in September in the American Journal of Health-System Pharmacy.
A goal is to increase the use of clinical pharmacists to help patients with mental health needs and pain management.
“This helps open up appointment slots for physicians to meet patients with acute care needs,” Ourth said.
Clinical pharmacists’ authority is determined at each VA hospital based on their training and knowledge.
The Madison VA allowed clinical pharmacists to take over management of patients with chronic diseases such as diabetes and high blood pressure, participate in weekly meetings with doctors and other members of patients’ care teams and handle patients’ calls about medications.
They typically see five patients in their office each day, usually for 30 minutes each, and they talk to another 10 by telephone, said Ellina Seckel, the clinical pharmacist who led the changes at the hospital.
Many issues involve adjusting medication dosages such as insulin, which do not require a face-to-face visit. When Seckel sees patients, she often helps them lower the number of drugs they take because they may cause unnecessary complications.
Expanding clinical pharmacists’ role in primary care has cut readmission rates and helped more patients keep their diabetes under control, Seckel said.
VA hospital officials in both Madison and El Paso said they faced challenges initially in persuading doctors to delegate some duties to qualified pharmacists.
“Some physicians feel like it’s a turf war and don’t want to refer their patients because they feel the clinical pharmacist is trying to practice medicine,” said Lanre’ Obisesan, a clinical pharmacist and assistant chief of pharmacy at the El Paso VA.
Even so, the El Paso VA’s average wait time fell from two months to two weeks, he said, after it added several clinical pharmacists and gave them independence to help patients. About 30 percent of the VA patients in El Paso have used clinical pharmacists, Obisesan said.
That share will rise. The hospital now has one clinical pharmacist for every six physicians, but it aims to add more pharmacists to reduce the ratio to 1 to 3.
The Madison VA is close to that ratio now after adding four clinical pharmacist positions in the past year.
Patients there can choose whether to see a doctor or a pharmacist. With approval from primary care physicians, pharmacists took over 27 percent of the follow-up appointments for patients with chronic illnesses, Seckel said.
That shift yields benefits for both doctors and patients, said Montgomery, the head of primary care services at the Madison VA.
Many VA doctors only have time to deal with patients’ acute care issues, such as knee or back pain, with little time to focus on a patient’s multiple chronic illnesses and often a dozen or more medications they may be taking for them.
“The more we can have members of the team to do routine things that do not require a physician’s time the better the quality of the visit and the better patient outcomes,” he said.
Patients seem to like what the hospital is doing.
Stephen Howard Foster saw a clinical pharmacist recently who told him he could stop taking one heartburn medication and switched him to another medicine to reduce side effects. He said he was comfortable with the pharmacist advising him without first consulting his physician and he saved time.
“This is a good idea rather than put up with normal delays,” said Foster, 51.
Another Madison VA patient, Mike Fonger, 71, saw clinical pharmacist Anita Kashyap recently to get a blood pressure check, lab test results, a review of his medications and to change an ointment he was taking for back and shoulder pain. Kashyap also helped him ease the side effects from the cholesterol-lowering drug he takes by cutting his dosage in half.
“I like the extra attention I get here,” Fonger said.
This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.
MADISON, WIS.— Something astonishing has happened in the past year to outpatient treatment at the Veterans Affairs hospital here.
Vets regularly get next-day and even same-day appointments for primary care now, no longer waiting a month or more to see a doctor as many once did.
The reason is they don’t all see doctors. Clinical pharmacists — whose special training permits them to prescribe drugs, order lab tests, make referrals to specialists and do physical examinations — are handling more patients’ chronic care needs. That frees physicians to concentrate on new patients and others with complex needs.
A quarter of primary care appointments at the Madison hospital are now handled by clinical pharmacists since they were integrated in patient care teams in 2015. Several VA hospitals — in El Paso, Texas, and Kansas City, Mo., among them — have followed Madison’s approach and more than 36 others are considering it, according to hospital officials.
“It’s made a tremendous positive impact in improving access,” said Dr. Jean Montgomery, chief of primary care services at the Madison hospital.
That’s critical for the VA, the focus of a national scandal in 2014 after news reports revealed the Phoenix VA hospital had booked primary care appointments months in advance, schedulers falsified wait times to make them look shorter and dozens had died awaiting care. Further investigations uncovered similar problems at other VA facilities. More than two years later, tens of thousands of vets are still waiting a month or two for an appointment, according to the latest data from the VA.
The Obama administration has allowed some veterans to seek care in the private sector if they choose, but VA wait times remain long and more action is needed, theGeneral Accountability Office reported in April.
Expanding clinical pharmacists’ role is a solution.
They receive two more years of education than regular pharmacists and they can handle many primary care needs for patients, particularly after physicians have diagnosed their conditions.
The VA has had them for more than 20 years, but their growing involvement in patient care is more recent. This year it employs 3,185 clinical pharmacists with authority to prescribe medications, order lab tests and perform physical assessments — nearly a 50 percent increase since 2011.
“It’s having a significant impact on reducing wait times and our office is trying to expand more of them nationally to increase access,” said Heather Ourth, national clinical program manager for VA Pharmacy Benefits Management Services.
In 2015, VA clinical pharmacists wrote 1.9 million prescriptions for chronic diseases, according to a report co-authored by Ourth and published in September in the American Journal of Health-System Pharmacy.
A goal is to increase the use of clinical pharmacists to help patients with mental health needs and pain management.
“This helps open up appointment slots for physicians to meet patients with acute care needs,” Ourth said.
Clinical pharmacists’ authority is determined at each VA hospital based on their training and knowledge.
The Madison VA allowed clinical pharmacists to take over management of patients with chronic diseases such as diabetes and high blood pressure, participate in weekly meetings with doctors and other members of patients’ care teams and handle patients’ calls about medications.
They typically see five patients in their office each day, usually for 30 minutes each, and they talk to another 10 by telephone, said Ellina Seckel, the clinical pharmacist who led the changes at the hospital.
Many issues involve adjusting medication dosages such as insulin, which do not require a face-to-face visit. When Seckel sees patients, she often helps them lower the number of drugs they take because they may cause unnecessary complications.
Expanding clinical pharmacists’ role in primary care has cut readmission rates and helped more patients keep their diabetes under control, Seckel said.
VA hospital officials in both Madison and El Paso said they faced challenges initially in persuading doctors to delegate some duties to qualified pharmacists.
“Some physicians feel like it’s a turf war and don’t want to refer their patients because they feel the clinical pharmacist is trying to practice medicine,” said Lanre’ Obisesan, a clinical pharmacist and assistant chief of pharmacy at the El Paso VA.
Even so, the El Paso VA’s average wait time fell from two months to two weeks, he said, after it added several clinical pharmacists and gave them independence to help patients. About 30 percent of the VA patients in El Paso have used clinical pharmacists, Obisesan said.
That share will rise. The hospital now has one clinical pharmacist for every six physicians, but it aims to add more pharmacists to reduce the ratio to 1 to 3.
The Madison VA is close to that ratio now after adding four clinical pharmacist positions in the past year.
Patients there can choose whether to see a doctor or a pharmacist. With approval from primary care physicians, pharmacists took over 27 percent of the follow-up appointments for patients with chronic illnesses, Seckel said.
That shift yields benefits for both doctors and patients, said Montgomery, the head of primary care services at the Madison VA.
Many VA doctors only have time to deal with patients’ acute care issues, such as knee or back pain, with little time to focus on a patient’s multiple chronic illnesses and often a dozen or more medications they may be taking for them.
“The more we can have members of the team to do routine things that do not require a physician’s time the better the quality of the visit and the better patient outcomes,” he said.
Patients seem to like what the hospital is doing.
Stephen Howard Foster saw a clinical pharmacist recently who told him he could stop taking one heartburn medication and switched him to another medicine to reduce side effects. He said he was comfortable with the pharmacist advising him without first consulting his physician and he saved time.
“This is a good idea rather than put up with normal delays,” said Foster, 51.
Another Madison VA patient, Mike Fonger, 71, saw clinical pharmacist Anita Kashyap recently to get a blood pressure check, lab test results, a review of his medications and to change an ointment he was taking for back and shoulder pain. Kashyap also helped him ease the side effects from the cholesterol-lowering drug he takes by cutting his dosage in half.
“I like the extra attention I get here,” Fonger said.
This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.
MADISON, WIS.— Something astonishing has happened in the past year to outpatient treatment at the Veterans Affairs hospital here.
Vets regularly get next-day and even same-day appointments for primary care now, no longer waiting a month or more to see a doctor as many once did.
The reason is they don’t all see doctors. Clinical pharmacists — whose special training permits them to prescribe drugs, order lab tests, make referrals to specialists and do physical examinations — are handling more patients’ chronic care needs. That frees physicians to concentrate on new patients and others with complex needs.
A quarter of primary care appointments at the Madison hospital are now handled by clinical pharmacists since they were integrated in patient care teams in 2015. Several VA hospitals — in El Paso, Texas, and Kansas City, Mo., among them — have followed Madison’s approach and more than 36 others are considering it, according to hospital officials.
“It’s made a tremendous positive impact in improving access,” said Dr. Jean Montgomery, chief of primary care services at the Madison hospital.
That’s critical for the VA, the focus of a national scandal in 2014 after news reports revealed the Phoenix VA hospital had booked primary care appointments months in advance, schedulers falsified wait times to make them look shorter and dozens had died awaiting care. Further investigations uncovered similar problems at other VA facilities. More than two years later, tens of thousands of vets are still waiting a month or two for an appointment, according to the latest data from the VA.
The Obama administration has allowed some veterans to seek care in the private sector if they choose, but VA wait times remain long and more action is needed, theGeneral Accountability Office reported in April.
Expanding clinical pharmacists’ role is a solution.
They receive two more years of education than regular pharmacists and they can handle many primary care needs for patients, particularly after physicians have diagnosed their conditions.
The VA has had them for more than 20 years, but their growing involvement in patient care is more recent. This year it employs 3,185 clinical pharmacists with authority to prescribe medications, order lab tests and perform physical assessments — nearly a 50 percent increase since 2011.
“It’s having a significant impact on reducing wait times and our office is trying to expand more of them nationally to increase access,” said Heather Ourth, national clinical program manager for VA Pharmacy Benefits Management Services.
In 2015, VA clinical pharmacists wrote 1.9 million prescriptions for chronic diseases, according to a report co-authored by Ourth and published in September in the American Journal of Health-System Pharmacy.
A goal is to increase the use of clinical pharmacists to help patients with mental health needs and pain management.
“This helps open up appointment slots for physicians to meet patients with acute care needs,” Ourth said.
Clinical pharmacists’ authority is determined at each VA hospital based on their training and knowledge.
The Madison VA allowed clinical pharmacists to take over management of patients with chronic diseases such as diabetes and high blood pressure, participate in weekly meetings with doctors and other members of patients’ care teams and handle patients’ calls about medications.
They typically see five patients in their office each day, usually for 30 minutes each, and they talk to another 10 by telephone, said Ellina Seckel, the clinical pharmacist who led the changes at the hospital.
Many issues involve adjusting medication dosages such as insulin, which do not require a face-to-face visit. When Seckel sees patients, she often helps them lower the number of drugs they take because they may cause unnecessary complications.
Expanding clinical pharmacists’ role in primary care has cut readmission rates and helped more patients keep their diabetes under control, Seckel said.
VA hospital officials in both Madison and El Paso said they faced challenges initially in persuading doctors to delegate some duties to qualified pharmacists.
“Some physicians feel like it’s a turf war and don’t want to refer their patients because they feel the clinical pharmacist is trying to practice medicine,” said Lanre’ Obisesan, a clinical pharmacist and assistant chief of pharmacy at the El Paso VA.
Even so, the El Paso VA’s average wait time fell from two months to two weeks, he said, after it added several clinical pharmacists and gave them independence to help patients. About 30 percent of the VA patients in El Paso have used clinical pharmacists, Obisesan said.
That share will rise. The hospital now has one clinical pharmacist for every six physicians, but it aims to add more pharmacists to reduce the ratio to 1 to 3.
The Madison VA is close to that ratio now after adding four clinical pharmacist positions in the past year.
Patients there can choose whether to see a doctor or a pharmacist. With approval from primary care physicians, pharmacists took over 27 percent of the follow-up appointments for patients with chronic illnesses, Seckel said.
That shift yields benefits for both doctors and patients, said Montgomery, the head of primary care services at the Madison VA.
Many VA doctors only have time to deal with patients’ acute care issues, such as knee or back pain, with little time to focus on a patient’s multiple chronic illnesses and often a dozen or more medications they may be taking for them.
“The more we can have members of the team to do routine things that do not require a physician’s time the better the quality of the visit and the better patient outcomes,” he said.
Patients seem to like what the hospital is doing.
Stephen Howard Foster saw a clinical pharmacist recently who told him he could stop taking one heartburn medication and switched him to another medicine to reduce side effects. He said he was comfortable with the pharmacist advising him without first consulting his physician and he saved time.
“This is a good idea rather than put up with normal delays,” said Foster, 51.
Another Madison VA patient, Mike Fonger, 71, saw clinical pharmacist Anita Kashyap recently to get a blood pressure check, lab test results, a review of his medications and to change an ointment he was taking for back and shoulder pain. Kashyap also helped him ease the side effects from the cholesterol-lowering drug he takes by cutting his dosage in half.
“I like the extra attention I get here,” Fonger said.
This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.
Test approved to screen donated blood for sickle cell trait
The US Food and Drug Administration (FDA) has approved use of the PreciseType HEA test to screen blood donors for sickle cell trait (SCT).
The test was previously FDA approved for use in determining blood compatibility between donors and transfusion recipients.
The added utility of screening donors for SCT addresses the desire to avoid transfusing red blood cells from SCT donors to neonates or patients with sickle cell disease.
Blood from SCT donors can also present a problem when performing the required filtration of white cells from the blood donation.
The PreciseType HEA test will allow these units to be identified prior to filtration and provide blood center staff with the opportunity to decide how best to utilize the various components of a whole blood donation.
The PreciseType HEA test is manufactured by BioArray Solutions, a wholly owned subsidiary of Immucor, Inc.
“We’ve successfully demonstrated the clinical benefits of our PreciseType HEA test, and this is evident in the FDA broadening its approved use,” said Michael Spigarelli, vice president of medical affairs at Immucor.
“The use of PreciseType HEA to screen donor units for patients with sickle cell disease, neonates, or any individual that may require SCT-negative blood provides a great improvement over previously used methods and offers the first FDA-approved molecular method specifically for screening units.”
SCT screening has traditionally been performed by solubility testing of sickle hemoglobin in buffer, but blood centers have been looking for an alternative due to limitations in this method.
According to Immucor, a molecular approach using PreciseType HEA can overcome the throughput limitations and reduce the false-positive rates observed with the traditional SCT screening method.
“We had already validated the PreciseType HEA test for [SCT screening] in our lab,” said Connie Westhoff, PhD, of the New York Blood Center in New York, New York.
“Our previous screening method required manual testing and interpretation of the results and had high false-positive rates. About 1 in 12 minority donors possess the sickle trait, so accurate results are important to us to avoid unnecessary notifications to donors and deferred blood units. We are now able to identify SCT in our donors utilizing the same PreciseType HEA test we are already running on many of our donors without running additional tests.” 
The US Food and Drug Administration (FDA) has approved use of the PreciseType HEA test to screen blood donors for sickle cell trait (SCT).
The test was previously FDA approved for use in determining blood compatibility between donors and transfusion recipients.
The added utility of screening donors for SCT addresses the desire to avoid transfusing red blood cells from SCT donors to neonates or patients with sickle cell disease.
Blood from SCT donors can also present a problem when performing the required filtration of white cells from the blood donation.
The PreciseType HEA test will allow these units to be identified prior to filtration and provide blood center staff with the opportunity to decide how best to utilize the various components of a whole blood donation.
The PreciseType HEA test is manufactured by BioArray Solutions, a wholly owned subsidiary of Immucor, Inc.
“We’ve successfully demonstrated the clinical benefits of our PreciseType HEA test, and this is evident in the FDA broadening its approved use,” said Michael Spigarelli, vice president of medical affairs at Immucor.
“The use of PreciseType HEA to screen donor units for patients with sickle cell disease, neonates, or any individual that may require SCT-negative blood provides a great improvement over previously used methods and offers the first FDA-approved molecular method specifically for screening units.”
SCT screening has traditionally been performed by solubility testing of sickle hemoglobin in buffer, but blood centers have been looking for an alternative due to limitations in this method.
According to Immucor, a molecular approach using PreciseType HEA can overcome the throughput limitations and reduce the false-positive rates observed with the traditional SCT screening method.
“We had already validated the PreciseType HEA test for [SCT screening] in our lab,” said Connie Westhoff, PhD, of the New York Blood Center in New York, New York.
“Our previous screening method required manual testing and interpretation of the results and had high false-positive rates. About 1 in 12 minority donors possess the sickle trait, so accurate results are important to us to avoid unnecessary notifications to donors and deferred blood units. We are now able to identify SCT in our donors utilizing the same PreciseType HEA test we are already running on many of our donors without running additional tests.”
The US Food and Drug Administration (FDA) has approved use of the PreciseType HEA test to screen blood donors for sickle cell trait (SCT).
The test was previously FDA approved for use in determining blood compatibility between donors and transfusion recipients.
The added utility of screening donors for SCT addresses the desire to avoid transfusing red blood cells from SCT donors to neonates or patients with sickle cell disease.
Blood from SCT donors can also present a problem when performing the required filtration of white cells from the blood donation.
The PreciseType HEA test will allow these units to be identified prior to filtration and provide blood center staff with the opportunity to decide how best to utilize the various components of a whole blood donation.
The PreciseType HEA test is manufactured by BioArray Solutions, a wholly owned subsidiary of Immucor, Inc.
“We’ve successfully demonstrated the clinical benefits of our PreciseType HEA test, and this is evident in the FDA broadening its approved use,” said Michael Spigarelli, vice president of medical affairs at Immucor.
“The use of PreciseType HEA to screen donor units for patients with sickle cell disease, neonates, or any individual that may require SCT-negative blood provides a great improvement over previously used methods and offers the first FDA-approved molecular method specifically for screening units.”
SCT screening has traditionally been performed by solubility testing of sickle hemoglobin in buffer, but blood centers have been looking for an alternative due to limitations in this method.
According to Immucor, a molecular approach using PreciseType HEA can overcome the throughput limitations and reduce the false-positive rates observed with the traditional SCT screening method.
“We had already validated the PreciseType HEA test for [SCT screening] in our lab,” said Connie Westhoff, PhD, of the New York Blood Center in New York, New York.
“Our previous screening method required manual testing and interpretation of the results and had high false-positive rates. About 1 in 12 minority donors possess the sickle trait, so accurate results are important to us to avoid unnecessary notifications to donors and deferred blood units. We are now able to identify SCT in our donors utilizing the same PreciseType HEA test we are already running on many of our donors without running additional tests.”
FDA grants drug orphan designation for CTCL
The US Food and Drug Administration (FDA) has granted orphan drug designation to TLC178 for the treatment of cutaneous T-cell lymphoma (CTCL).
TLC178 is a liposomal-encapsulated formulation of the chemotherapy drug vinorelbine, which is FDA approved to treat non-small cell lung cancer.
The goal with TLC178 is to improve the efficacy and decrease the toxicity of vinorelbine to extend the indication beyond solid tumors into lymphoma.
A proprietary technology known as NanoX™ is used to load vinorelbine into liposomes designed to target tumor-specific cell-surface epitopes, extend the circulation time of the drug, increase the concentation of drug delivered to tumor cells, and decrease side effects.
TLC178 is being developed by Taiwan Liposome Company.
The company recently received US FDA approval for its phase 1/2 study (NCT02925000) investigating TLC178 in patients with advanced cancers, including CTCL and other lymphomas.
This trial is planned for sites in Taiwan and the US. The trial will be initiated in Taiwan once approval is granted by the Taiwan FDA.
About orphan designation
The US FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to TLC178 for the treatment of cutaneous T-cell lymphoma (CTCL).
TLC178 is a liposomal-encapsulated formulation of the chemotherapy drug vinorelbine, which is FDA approved to treat non-small cell lung cancer.
The goal with TLC178 is to improve the efficacy and decrease the toxicity of vinorelbine to extend the indication beyond solid tumors into lymphoma.
A proprietary technology known as NanoX™ is used to load vinorelbine into liposomes designed to target tumor-specific cell-surface epitopes, extend the circulation time of the drug, increase the concentation of drug delivered to tumor cells, and decrease side effects.
TLC178 is being developed by Taiwan Liposome Company.
The company recently received US FDA approval for its phase 1/2 study (NCT02925000) investigating TLC178 in patients with advanced cancers, including CTCL and other lymphomas.
This trial is planned for sites in Taiwan and the US. The trial will be initiated in Taiwan once approval is granted by the Taiwan FDA.
About orphan designation
The US FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to TLC178 for the treatment of cutaneous T-cell lymphoma (CTCL).
TLC178 is a liposomal-encapsulated formulation of the chemotherapy drug vinorelbine, which is FDA approved to treat non-small cell lung cancer.
The goal with TLC178 is to improve the efficacy and decrease the toxicity of vinorelbine to extend the indication beyond solid tumors into lymphoma.
A proprietary technology known as NanoX™ is used to load vinorelbine into liposomes designed to target tumor-specific cell-surface epitopes, extend the circulation time of the drug, increase the concentation of drug delivered to tumor cells, and decrease side effects.
TLC178 is being developed by Taiwan Liposome Company.
The company recently received US FDA approval for its phase 1/2 study (NCT02925000) investigating TLC178 in patients with advanced cancers, including CTCL and other lymphomas.
This trial is planned for sites in Taiwan and the US. The trial will be initiated in Taiwan once approval is granted by the Taiwan FDA.
About orphan designation
The US FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Resource use lower for patients on dabigatran, data suggest
Photo by ec-jpr
Real-world data suggest that, in the first year of treatment with an anticoagulant, patients with non-valvular atrial fibrillation tend to use fewer healthcare resources if they receive dabigatran rather than warfarin.
Patients treated with dabigatran experienced fewer all-cause hospitalizations, emergency room (ER) visits, and physician office visits than patients treated with warfarin.
These findings were published in The American Journal of Pharmacy Benefits.
The research was supported by Boehringer Ingelheim Pharmaceuticals, Inc., the company that markets dabigatran as Pradaxa.
“While there are many published studies comparing the clinical outcomes of [dabigatran] and warfarin, this is one of the first to compare their respective impact on the use of healthcare resources,” said study author Matthew Sussman, of Boston Health Economics, Inc. in Waltham, Massachusetts.
“Beyond data from clinical studies, it is important for physicians to also understand the experiences patients have in real-world settings, including the economic considerations of their treatment choices.”
Sussman and his colleagues analyzed data on 3890 patients newly diagnosed with non-valvular atrial fibrillation—1945 treated with dabigatran and 1945 treated with warfarin—using de-identified electronic health records from a large, nationwide database of US integrated delivery networks.
Patients in the warfarin cohort were propensity-score matched 1:1 to patients in the dabigatran cohort and were followed up to 1 year after initiating therapy to assess all-cause, stroke-related, and bleed-related healthcare resource use.
The researchers found that dabigatran-treated patients had a significantly lower number of mean per-patient per-year (PPPY) hospitalizations (1.07 vs 1.20, P<0.001), ER visits (0.36 vs 0.51, P<0.001), and physician office visits (10.64 vs 18.13, P<0.001) than patients treated with warfarin.
When it came to stroke-related resource use, dabigatran-treated patients had a significantly lower number of mean PPPY hospitalizations (0.06 vs 0.10, P=0.03) and physician office visits (0.16 vs 0.29, P=0.02). But the difference in ER visits between the dabigatran and warfarin groups was not significant (0 vs 0.01, P=0.65).
As for bleed-related resource use, there was no significant difference between the dabigatran and warfarin groups with regard to the mean number of PPPY hospitalizations (0.05 vs 0. 03, P=0.49) or physician office visits (0.05 vs 0.15, P=0.57). But the difference in ER visits was significant (0.01 vs 0.03, P=0.02).
Photo by ec-jpr
Real-world data suggest that, in the first year of treatment with an anticoagulant, patients with non-valvular atrial fibrillation tend to use fewer healthcare resources if they receive dabigatran rather than warfarin.
Patients treated with dabigatran experienced fewer all-cause hospitalizations, emergency room (ER) visits, and physician office visits than patients treated with warfarin.
These findings were published in The American Journal of Pharmacy Benefits.
The research was supported by Boehringer Ingelheim Pharmaceuticals, Inc., the company that markets dabigatran as Pradaxa.
“While there are many published studies comparing the clinical outcomes of [dabigatran] and warfarin, this is one of the first to compare their respective impact on the use of healthcare resources,” said study author Matthew Sussman, of Boston Health Economics, Inc. in Waltham, Massachusetts.
“Beyond data from clinical studies, it is important for physicians to also understand the experiences patients have in real-world settings, including the economic considerations of their treatment choices.”
Sussman and his colleagues analyzed data on 3890 patients newly diagnosed with non-valvular atrial fibrillation—1945 treated with dabigatran and 1945 treated with warfarin—using de-identified electronic health records from a large, nationwide database of US integrated delivery networks.
Patients in the warfarin cohort were propensity-score matched 1:1 to patients in the dabigatran cohort and were followed up to 1 year after initiating therapy to assess all-cause, stroke-related, and bleed-related healthcare resource use.
The researchers found that dabigatran-treated patients had a significantly lower number of mean per-patient per-year (PPPY) hospitalizations (1.07 vs 1.20, P<0.001), ER visits (0.36 vs 0.51, P<0.001), and physician office visits (10.64 vs 18.13, P<0.001) than patients treated with warfarin.
When it came to stroke-related resource use, dabigatran-treated patients had a significantly lower number of mean PPPY hospitalizations (0.06 vs 0.10, P=0.03) and physician office visits (0.16 vs 0.29, P=0.02). But the difference in ER visits between the dabigatran and warfarin groups was not significant (0 vs 0.01, P=0.65).
As for bleed-related resource use, there was no significant difference between the dabigatran and warfarin groups with regard to the mean number of PPPY hospitalizations (0.05 vs 0. 03, P=0.49) or physician office visits (0.05 vs 0.15, P=0.57). But the difference in ER visits was significant (0.01 vs 0.03, P=0.02).
Photo by ec-jpr
Real-world data suggest that, in the first year of treatment with an anticoagulant, patients with non-valvular atrial fibrillation tend to use fewer healthcare resources if they receive dabigatran rather than warfarin.
Patients treated with dabigatran experienced fewer all-cause hospitalizations, emergency room (ER) visits, and physician office visits than patients treated with warfarin.
These findings were published in The American Journal of Pharmacy Benefits.
The research was supported by Boehringer Ingelheim Pharmaceuticals, Inc., the company that markets dabigatran as Pradaxa.
“While there are many published studies comparing the clinical outcomes of [dabigatran] and warfarin, this is one of the first to compare their respective impact on the use of healthcare resources,” said study author Matthew Sussman, of Boston Health Economics, Inc. in Waltham, Massachusetts.
“Beyond data from clinical studies, it is important for physicians to also understand the experiences patients have in real-world settings, including the economic considerations of their treatment choices.”
Sussman and his colleagues analyzed data on 3890 patients newly diagnosed with non-valvular atrial fibrillation—1945 treated with dabigatran and 1945 treated with warfarin—using de-identified electronic health records from a large, nationwide database of US integrated delivery networks.
Patients in the warfarin cohort were propensity-score matched 1:1 to patients in the dabigatran cohort and were followed up to 1 year after initiating therapy to assess all-cause, stroke-related, and bleed-related healthcare resource use.
The researchers found that dabigatran-treated patients had a significantly lower number of mean per-patient per-year (PPPY) hospitalizations (1.07 vs 1.20, P<0.001), ER visits (0.36 vs 0.51, P<0.001), and physician office visits (10.64 vs 18.13, P<0.001) than patients treated with warfarin.
When it came to stroke-related resource use, dabigatran-treated patients had a significantly lower number of mean PPPY hospitalizations (0.06 vs 0.10, P=0.03) and physician office visits (0.16 vs 0.29, P=0.02). But the difference in ER visits between the dabigatran and warfarin groups was not significant (0 vs 0.01, P=0.65).
As for bleed-related resource use, there was no significant difference between the dabigatran and warfarin groups with regard to the mean number of PPPY hospitalizations (0.05 vs 0. 03, P=0.49) or physician office visits (0.05 vs 0.15, P=0.57). But the difference in ER visits was significant (0.01 vs 0.03, P=0.02).
Team identifies genetic hallmarks of B-ALL subtype
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers say they have uncovered a unique paradigm of transcription factor deregulation in B-precursor acute lymphoblastic leukemia (B-ALL).
The team found that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-ALL that may comprise up to 8% of B-ALL cases.
The researchers reported these findings in Nature Genetics.
“Our work is motivated by a lack of information on the genetic basis of many B-ALL cases,” said study author Charles Mullighan, MBBS, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“We discovered a distinct gene pattern in blood samples from some patients in our study and wanted to determine the underlying molecular events behind this signal.”
The researchers studied a group of 1913 B-ALL patients (including children, adolescents, and young adults) to understand the genetic basis of the disease.
Microarray and transcriptome sequencing revealed that 7.6% of these patients had the distinctive genetic profile the researchers wanted to characterize further.
“Our work revealed that, in this type of B-ALL, there is a sequence of molecular events that involves the interplay of 2 transcription factors,” Dr Mullighan said.
The team observed rearrangement of the gene DUX4 in all cases of this subtype of B-ALL, which resulted in high-level expression of DUX4. DUX4 was shown to bind to the ERG gene, leading to deregulated expression of ERG.
The deregulation of ERG compromised the function of ERG either by deleting part of the gene or by expressing another form of ERG—ERGalt. In both cases, loss of activity was observed for the ERG transcription factor, which led to leukemia.
“These results underscore that there is still more to be learned about the genetic changes in ALL, and that this knowledge can help refine treatment for patients,” said study author Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.
The researchers hope identification of the relationships between the 2 transcription factors will lead to new diagnostic tests for patients. DUX4/ERG ALL is linked to favorable outcomes even when other detrimental genetic mutations are present.
Currently, only transcriptome or genome sequencing helps identify the DUX4 rearrangements. The researchers say other detection methods, such as fluorescence hybridization or karyotyping, are not sufficient to recognize genetic changes to DUX4.
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers say they have uncovered a unique paradigm of transcription factor deregulation in B-precursor acute lymphoblastic leukemia (B-ALL).
The team found that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-ALL that may comprise up to 8% of B-ALL cases.
The researchers reported these findings in Nature Genetics.
“Our work is motivated by a lack of information on the genetic basis of many B-ALL cases,” said study author Charles Mullighan, MBBS, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“We discovered a distinct gene pattern in blood samples from some patients in our study and wanted to determine the underlying molecular events behind this signal.”
The researchers studied a group of 1913 B-ALL patients (including children, adolescents, and young adults) to understand the genetic basis of the disease.
Microarray and transcriptome sequencing revealed that 7.6% of these patients had the distinctive genetic profile the researchers wanted to characterize further.
“Our work revealed that, in this type of B-ALL, there is a sequence of molecular events that involves the interplay of 2 transcription factors,” Dr Mullighan said.
The team observed rearrangement of the gene DUX4 in all cases of this subtype of B-ALL, which resulted in high-level expression of DUX4. DUX4 was shown to bind to the ERG gene, leading to deregulated expression of ERG.
The deregulation of ERG compromised the function of ERG either by deleting part of the gene or by expressing another form of ERG—ERGalt. In both cases, loss of activity was observed for the ERG transcription factor, which led to leukemia.
“These results underscore that there is still more to be learned about the genetic changes in ALL, and that this knowledge can help refine treatment for patients,” said study author Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.
The researchers hope identification of the relationships between the 2 transcription factors will lead to new diagnostic tests for patients. DUX4/ERG ALL is linked to favorable outcomes even when other detrimental genetic mutations are present.
Currently, only transcriptome or genome sequencing helps identify the DUX4 rearrangements. The researchers say other detection methods, such as fluorescence hybridization or karyotyping, are not sufficient to recognize genetic changes to DUX4.
Photo courtesy of St. Jude
Children’s Research Hospital
Researchers say they have uncovered a unique paradigm of transcription factor deregulation in B-precursor acute lymphoblastic leukemia (B-ALL).
The team found that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-ALL that may comprise up to 8% of B-ALL cases.
The researchers reported these findings in Nature Genetics.
“Our work is motivated by a lack of information on the genetic basis of many B-ALL cases,” said study author Charles Mullighan, MBBS, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“We discovered a distinct gene pattern in blood samples from some patients in our study and wanted to determine the underlying molecular events behind this signal.”
The researchers studied a group of 1913 B-ALL patients (including children, adolescents, and young adults) to understand the genetic basis of the disease.
Microarray and transcriptome sequencing revealed that 7.6% of these patients had the distinctive genetic profile the researchers wanted to characterize further.
“Our work revealed that, in this type of B-ALL, there is a sequence of molecular events that involves the interplay of 2 transcription factors,” Dr Mullighan said.
The team observed rearrangement of the gene DUX4 in all cases of this subtype of B-ALL, which resulted in high-level expression of DUX4. DUX4 was shown to bind to the ERG gene, leading to deregulated expression of ERG.
The deregulation of ERG compromised the function of ERG either by deleting part of the gene or by expressing another form of ERG—ERGalt. In both cases, loss of activity was observed for the ERG transcription factor, which led to leukemia.
“These results underscore that there is still more to be learned about the genetic changes in ALL, and that this knowledge can help refine treatment for patients,” said study author Stephen Hunger, MD, of the Children’s Hospital of Philadelphia in Pennsylvania.
The researchers hope identification of the relationships between the 2 transcription factors will lead to new diagnostic tests for patients. DUX4/ERG ALL is linked to favorable outcomes even when other detrimental genetic mutations are present.
Currently, only transcriptome or genome sequencing helps identify the DUX4 rearrangements. The researchers say other detection methods, such as fluorescence hybridization or karyotyping, are not sufficient to recognize genetic changes to DUX4.
DoD Offers ‘Drug Take Back’ Program
Unwanted, unused, and expired prescription drugs are a major contributor to prescription drug abuse, according to the Office of National Drug Control Policy. And nearly one third of suicide attempts among veterans involve prescription medicines. But a change in the rules at the Drug Enforcement Administration now allows military treatment facilities to accept and dispose of those unused medications. The Department of Defense was the first federal agency to put the “Drug Take Back” program into effect nationwide for its beneficiaries.
Military treatment facility pharmacies can accept legal prescription and over-the-counter bottled pills, tablets and capsules, ointments, creams, lotions, powders, and liquid medicines that are no more than 4 ounces. (Pet medicines are included.)
Patients can take the drugs to their faculty or send them by mail in a special envelope available at some military treatment facility pharmacies.
Bringing back the drugs not only helps the environment by reducing the amount of drugs that can filter through water supplies and landfills, but it also cuts down on the risk of accidental or intentional drug misuse. “DoD and the [Military Health System] are committed to reducing the risk of prescription and over-the-counter drug abuse in the military community, supporting the nation’s efforts to reduce opioid abuse,” said Dr. George Jones, chief of the Defense Health Agency’s Pharmacy Operations Division, in a news report on health.mil.
Unwanted, unused, and expired prescription drugs are a major contributor to prescription drug abuse, according to the Office of National Drug Control Policy. And nearly one third of suicide attempts among veterans involve prescription medicines. But a change in the rules at the Drug Enforcement Administration now allows military treatment facilities to accept and dispose of those unused medications. The Department of Defense was the first federal agency to put the “Drug Take Back” program into effect nationwide for its beneficiaries.
Military treatment facility pharmacies can accept legal prescription and over-the-counter bottled pills, tablets and capsules, ointments, creams, lotions, powders, and liquid medicines that are no more than 4 ounces. (Pet medicines are included.)
Patients can take the drugs to their faculty or send them by mail in a special envelope available at some military treatment facility pharmacies.
Bringing back the drugs not only helps the environment by reducing the amount of drugs that can filter through water supplies and landfills, but it also cuts down on the risk of accidental or intentional drug misuse. “DoD and the [Military Health System] are committed to reducing the risk of prescription and over-the-counter drug abuse in the military community, supporting the nation’s efforts to reduce opioid abuse,” said Dr. George Jones, chief of the Defense Health Agency’s Pharmacy Operations Division, in a news report on health.mil.
Unwanted, unused, and expired prescription drugs are a major contributor to prescription drug abuse, according to the Office of National Drug Control Policy. And nearly one third of suicide attempts among veterans involve prescription medicines. But a change in the rules at the Drug Enforcement Administration now allows military treatment facilities to accept and dispose of those unused medications. The Department of Defense was the first federal agency to put the “Drug Take Back” program into effect nationwide for its beneficiaries.
Military treatment facility pharmacies can accept legal prescription and over-the-counter bottled pills, tablets and capsules, ointments, creams, lotions, powders, and liquid medicines that are no more than 4 ounces. (Pet medicines are included.)
Patients can take the drugs to their faculty or send them by mail in a special envelope available at some military treatment facility pharmacies.
Bringing back the drugs not only helps the environment by reducing the amount of drugs that can filter through water supplies and landfills, but it also cuts down on the risk of accidental or intentional drug misuse. “DoD and the [Military Health System] are committed to reducing the risk of prescription and over-the-counter drug abuse in the military community, supporting the nation’s efforts to reduce opioid abuse,” said Dr. George Jones, chief of the Defense Health Agency’s Pharmacy Operations Division, in a news report on health.mil.
Allergic Rhinitis
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The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Inherited Thrombophilia Testing
The Things We Do for No Reason (TWDFNR) series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent black and white conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/
Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of venous thromboembolism (VTE). This disorder is prevalent in approximately 7% of the population and includes mutations such as factor V Leiden, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin deficiency, and methylene tetrahydrofolate reductase. The relative risk of VTE is 3‐ to 20‐fold greater in patients with inherited thrombophilia compared with the general population. Is testing for inherited thrombophilia recommended? The available evidence suggests that testing for inherited thrombophilia is not recommended in most clinical settings. In patients without a personal history of VTE, thrombophilia results do not change management, as there is no evidence to support thromboprophylaxis in this setting. In patients with a personal history of provoked or unprovoked VTE, inpatient testing is not indicated, as results do not influence management, testing is not cost‐effective, and a positive test result may lead to unnecessary patient anxiety or may result in unnecessary involvement of consultants. Testing in hospitalized patients has even more limitations because many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation.
CASE PRESENTATION
A 23‐year‐old man presents to the emergency room with pleuritic chest pain and new oxygen requirement of 2 L nasal cannula. He has a history of unprovoked lower extremity deep venous thrombosis (DVT) diagnosed at age 20 and completed 3 months of systemic anticoagulation without complications. He reports no family history of clotting disorders or venous thromboembolism (VTE) and no reversible risk factors for VTE such as prolonged immobility, recent surgery, or high‐risk medications. A computed tomogram pulmonary embolism protocol shows multiple right lower lobe, segmental pulmonary emboli. Anticoagulation is initiated, and the patient is admitted to the hospital. Will inpatient inherited thrombophilia testing impact management for this case?
WHY MAY INHERITED THROMBOPHILIA TESTING PROVE HELPFUL?
The annual incidence rate of a first VTE event is estimated as 117 per 100,000 individuals per year.[1] The most common presentations are symptomatic DVT of the leg (annual incidence approximately 48 per 100,000 people), or a pulmonary embolism (annual incidence approximately 69 per 100,000 people).[1] Pulmonary embolism results in death in up to 30% of untreated patients and 2.5% of patients who receive systemic anticoagulation.[2] Principal in the pathogenesis of VTE are factors described by Virchow's triad: venous stasis, endothelial injury, and systemic hypercoagulability. By identifying a mutation in 1 or more of the factors in the clotting pathway, an evaluation for inherited thrombophilia theoretically may unearth factors that drive systemic hypercoagulability and inform decision making so as to prevent future events.
Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of VTE.[3] Approximately 7% of the general population has inherited thrombophilia, which includes factor V Leiden (FVL) mutation, prothrombin 20210 mutation (PT20210), protein C deficiency, protein S deficiency, antithrombin III (ATIII) deficiency, and methylene tetrahydrofolate reductase mutation (MTHFR).[4] Of note, the definition does not include acquired etiologies, such as antiphospholipid antibody syndrome. Depending on the underlying condition and expression of the genetic abnormality, the relative risk of VTE in patients with inherited thrombophilia is 3‐ to 20‐fold greater than that of the general population.[5] Therefore, it is logical to consider that testing for inherited thrombophilia might be clinically useful. However, the evidence for doing so is very limited.
DOES INHERITED THROMBOPHILIA TESTING CHANGE MANAGEMENT?
An inherited thrombophilia evaluation is unlikely to affect management in most clinical settings. There is no current evidence to support primary prophylaxis[6] nor is there evidence that management of patients with recurrent VTE should be altered in the setting of inherited thrombophilia.
To date, no prospective trials have evaluated the efficacy of anticoagulant use for primary prevention of VTE in patients with inherited thrombophilia.[6] Given the limited evidence for thromboprophylaxis and risks of anticoagulation, primary prevention for patients with inherited thrombophilia that remain asymptomatic is not recommended by the current American College of Chest Physicians guidelines.[7, 8]
Similarly, in patients with a first VTE or recurrent VTE, diagnosis of inherited thrombophilia is often not associated with recurrent events, which suggests that other nongenetic factors may be just as important, if not more important, in determining the risk of recurrence.[9] Although no randomized controlled or controlled clinical trials have evaluated the effects of testing for inherited thrombophilia on recurrent VTE,[10, 11] several prospective studies have assessed risk factors for recurrence. Data from these studies suggest that recurrence rates after unprovoked VTE are only weakly correlated with inherited thrombophilia status.[12, 13] Rather, it is postulated that patients with recurrent VTE may exhibit a prothrombotic tendency regardless of underlying genetic predisposition. In this case, decisions regarding anticoagulation do not vary by thrombophilia status. Instead, thrombophilia testing may divert attention away from the management of more prevalent, potentially modifiable risk factors such as immobility, oral contraceptive use, or malignancy, all of which are associated with recurrent VTE.[14] These provoking factors are the most important determinants of the chance of VTE recurrence as well as the most significant factors to take into account when deciding duration of anticoagulation.
Christiansen et al. performed a prospective study evaluating the association between recurrent VTE and thrombophilia status. After following 474 patients with confirmed first episode VTE for a mean of 7.3 years, no statistically significant risk of VTE was found for patients with FVL (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.7‐1.9), PT20210 (HR: 0.7, 95% CI: 0.3‐2.0), or an anticoagulant (protein C, protein S or ATIII) deficiency (HR: 1.8, 95% CI: 0.9‐3.7).[15] Although unexplained VTE was statistically associated with VTE recurrence, heritable thrombophilia status was not.
In a systematic review and meta‐analysis investigating the association of FVL and PT20210 with recurrent VTE, Ho and colleagues found a statistically significant risk of recurrent VTE in patients with inherited thrombophilia due to FVL (odds ratio [OR]: 1.41, 95% CI: 1.14‐1.75) and PT20210 (OR: 1.72, 95% CI: 1.27‐2.31), and reported that at most, only up to 1 in 6 recurrent VTEs may be attributable to these mutations.[16] Based on this relatively modest effect, the authors question the utility of testing for inherited thrombophilia, as thrombophilia status is unlikely to warrant a change in type or duration of treatment.
Regardless of whether an underlying inherited thrombophilia is identified, patients with history of recurrent VTE are often candidates for long‐term anticoagulation. Testing for inherited thrombophilia in patients with prior VTE events will therefore not influence decisions regarding clinical management. Additionally, such testing may be confounded by ongoing disease or treatment (Table 1). For example, protein C, protein S antigen, and ATIII levels are low in the setting of acute VTE.[17, 18] Likewise, protein C and S (vitamin Kdependent proteins) will be low in the setting of anticoagulation with warfarin.[19] Moreover, ATIII activity and antigen levels are low in the setting of heparin use.[20] Lack of provider awareness regarding these interactions may have important negative consequences, including a spurious diagnosis of thrombophilia,[21, 22] unnecessary hematology consultation, and psychological distress to patients in the form of ongoing unwarranted testing or apprehension regarding recurrence.[23]
| Acute VTE | Anticoagulation With Warfarin | Anticoagulation With NOACs | Anticoagulation With Heparin/LMWH | |
|---|---|---|---|---|
| ||||
| FVL/PT20210/MTHFR gene mutations | No Impact | No Impact | No Impact | No Impact |
| Protein C* | Decreased | Decreased | No impact | No impact |
| Protein S* | Decreased | Decreased | No impact | No impact |
| ATIII activity | Decreased | Slight increase | Slight increase | Decreased |
| ATIII antigen | Decreased | Slight increase | Slight increase | Decreased |
Additionally, this expensive evaluation has estimated direct costs of $1100 to $2400 per thrombophilia panel based on estimation of charges billed by a large commercial laboratory.[24, 25] In 2014, over 280,000 claims were submitted under Medicare Part B across all care settings for a thrombophilia analysis including FVL, PT20210, and MTHFR gene mutations,[24] which would equate to between $300 million to $672 million.[26] Unfortunately, there have been no large‐scale trials to assess cost‐effectiveness. However, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stated that cost‐effectiveness modeling studies in this area require updating with current VTE risk estimates but are suggestive that routine FVL/PT20210 testing is not cost‐effective.[27]
ARE THERE CIRCUMSTANCES IN WHICH INPATIENT INHERITED THROMBOPHILIA TESTING PROVES BENEFICIAL?
The evidence for when to test for inherited thrombophilia is very limited and is often based on individualized risk. The current EGAPP guidelines acknowledge this limitation, specifically noting that there is a paucity of data evaluating management or prophylaxis of patients with homozygous or compound heterozygous FVL or P20210 mutation, and a lack of data surrounding whether or not knowledge of thrombophilia mutation should affect anticoagulation treatment.[27] This is why an individualized approach is deemed necessary. For example, the decision to prescribe hormone replacement therapy in women with a family history of inherited thrombophilia may be better informed by testing prior to treatment. Similarly, pregnant women with a family history or personal history of VTE may also benefit from inherited thrombophilia testing, as this may influence antepartum or postpartum management.[28, 29] The National Institute for Health and Clinical Excellence (NICE) guidelines recommend consideration of testing for hereditary thrombophilia in patients with unprovoked VTE and a first‐degree relative with VTE, if stopping anticoagulation treatment is planned; however, these recommendations are based solely on Guideline Development Group's experience and opinion.[30] Regardless, testing for inherited thrombophilia has significant potential consequences. Patients at risk should meet with an outpatient hematologist and/or a genetic counselor, if available, to determine the risks and benefits of testing.
WHAT DO GUIDELINES SAY ABOUT INHERITED THROMBOPHILIA TESTING?
The most recent NICE guidelines recommend against offering inherited thrombophilia testing to patients presenting with a provoked VTE in any clinical setting.[30] In patients diagnosed with unprovoked VTE, testing should not be considered unless a first degree relative with a history of VTE exists.[30] The NICE guidelines also recommend against routinely offering thrombophilia testing to asymptomatic first‐degree relatives of patients with a history of VTE or known inherited thrombophilia. This recommendation is reflected in the American Society of Hematology's Choosing Wisely recommendations since 2013.[31] Further, The American College of Medical Genetics and Genomics' Choosing Wisely recommendations from 2015 state that MTHFR mutations should never be included in any thrombophilia workup, as recent meta‐analyses have disproven an association between the presence of these variants and venous thromboembolism.[32]
The EGAPP Working Group recommends against routine testing for FVL or PT20210 in patients who present with an idiopathic VTE, as longer‐term anticoagulation offers similar benefits to patients with or without these mutations.[27] EGAPP also recommends against testing asymptomatic adult family members of patients with VTE and/or an FVL or PT20210 mutation for the purpose of considering primary prophylactic anticoagulation. In these circumstances, it is felt that the potential risks of thrombophilia testing outweigh any potential benefits.
HOW SHOULD HOSPITALISTS APPROACH TESTING OF INHERITED THROMBOPHILIA?
The providers in our case presentation are challenged with determining whether inpatient thrombophilia evaluation will add value to the evaluation of patients with unprovoked VTE. The available evidence suggests that clinicians should avoid ordering thrombophilia testing for hospitalized patients with unprovoked VTE because (1) many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation, (2) results of testing often do not influence management, (3) testing is not cost‐effective, (4) a positive test result may lead to unnecessary patient anxiety, and (5) testing may result in inappropriately prolonged anticoagulation courses or unnecessary involvement of inpatient consultants. For these reasons, the patient in our case presentation should not be tested for inherited thrombophilia. In patients with personal or family histories of recurrent thromboembolism, modifiable clinical risk factors should be addressed, as these are more likely to influence treatment decisions compared to genetic testing. Finally, patients may be referred to an outpatient hematologist or geneticist for individualized discussions of risks and benefits of testing for inherited thrombophilia.
CONCLUSION
Inpatient evaluation for inherited thrombophilia for VTE is not clinically useful, cost‐effective, or reliable in the setting of VTE. The result of such testing does not affect management of acute primary or recurrent VTE. Testing should only be considered using an individualized approach in the outpatient setting with appropriate genetic counseling.
Disclosure: Christopher M. Petrilli, MD, and Lauren Heidemann, MD, contributed equally to this work. The authors report no conflicts of interest.
Do you think this is a low‐value practice? Is this truly a Thing We Do for No Reason? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other Things We Do for No Reason topics by emailing [email protected].
- , , , , , . Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25‐year population‐based study. Arch Intern Med. 1998;158(6):585–593.
- , , , et al. The clinical course of pulmonary embolism. N Engl J Med. 1992;326(19):1240–1245.
- , . Hereditary thrombophilia. Thromb J. 2006;4:15.
- , , , . Deep‐vein thrombosis. Lancet. 1999;353(9151):479–485.
- , , , et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450–2457.
- , , , et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S–e736S.
- , . Testing for inherited thrombophilia and consequences for antithrombotic prophylaxis in patients with venous thromboembolism and their relatives. A review of the Guidelines from Scientific Societies and Working Groups. Thromb Haemost. 2013;110(4):697–705.
- , , , et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S–e226S.
- , , , et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301(23):2472–2485.
- , , , . Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst Rev. 2009;(1):CD007069.
- , , , . Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst Rev. 2012;12:CD007069.
- , , , . Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362(9383):523–526.
- , , , et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood. 2008;112(12):4432–4436.
- , . Testing for thrombophilia: an evidence‐based approach. Postgrad Med J. 2006;82(973):699–704.
- , , , , . Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA. 2005;293(19):2352–2361.
- , , , . Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med. 2006;166(7):729–736.
- , , , . Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest. 1986;77(2):416–425.
- , . Inherited antithrombin deficiency: a review. Haemophilia. 2008;14(6):1229–1239.
- , , , . Decline of proteins C and S and factors II, VII, IX and X during the initiation of warfarin therapy. Thromb Res. 1987;45(6):783–790.
- . Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007:127–135.
- , , . Activated protein C resistance testing for factor V Leiden. Am J Hematol. 2014;89(12):1147–1150.
- , . Quantitation of human protein S in the plasma of normal and warfarin‐treated individuals by radioimmunoassay. Thromb Res. 1984;36(6):527–535.
- , , , . Social aspects of genetic testing for factor V Leiden mutation in healthy individuals and their importance for daily practice. Thromb Res. 2004;113(1):7–12.
- , . Hypercoagulability: clinical assessment and treatment. South Med J. 2001;94(10):1013–1020.
- , , . An evaluation of thrombophilia screening in an urban tertiary care medical center: A “real world” experience. Am J Clin Pathol. 2006;126(1):120–127.
- CodeMap. Available at: https://www.codemap.com. Accessed January 18, 2016.
- Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Genet Med. 2011;13(1):67–76.
- , , , et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group. N Engl J Med. 2000;343(20):1439–1444.
- , , , et al. Frequency of pregnancy‐related venous thromboembolism in anticoagulant factor‐deficient women: implications for prophylaxis. Ann Intern Med. 1996;125(12):955–960.
- , , , ; Guideline Development Group. Management of venous thromboembolic diseases and the role of thrombophilia testing: summary of NICE guidance. BMJ. 2012;344:e3979.
- American Society of Hematology. Ten things physicians and patients should question. Choosing Wisely website. Available at: http://www.choosingwisely.org/societies/american‐society‐of‐hematology. Published December 4, 2013. Accessed January 18, 2016.
- American College of Medical Genetics and Genomics. Five Things patients and providers should question. Choosing Wisely website. Available at: http://www.choosingwisely.org/societies/american‐college‐of‐medical‐genetics‐and‐genomics. Published July 10, 2015. Accessed March 13, 2016.
The Things We Do for No Reason (TWDFNR) series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent black and white conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/
Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of venous thromboembolism (VTE). This disorder is prevalent in approximately 7% of the population and includes mutations such as factor V Leiden, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin deficiency, and methylene tetrahydrofolate reductase. The relative risk of VTE is 3‐ to 20‐fold greater in patients with inherited thrombophilia compared with the general population. Is testing for inherited thrombophilia recommended? The available evidence suggests that testing for inherited thrombophilia is not recommended in most clinical settings. In patients without a personal history of VTE, thrombophilia results do not change management, as there is no evidence to support thromboprophylaxis in this setting. In patients with a personal history of provoked or unprovoked VTE, inpatient testing is not indicated, as results do not influence management, testing is not cost‐effective, and a positive test result may lead to unnecessary patient anxiety or may result in unnecessary involvement of consultants. Testing in hospitalized patients has even more limitations because many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation.
CASE PRESENTATION
A 23‐year‐old man presents to the emergency room with pleuritic chest pain and new oxygen requirement of 2 L nasal cannula. He has a history of unprovoked lower extremity deep venous thrombosis (DVT) diagnosed at age 20 and completed 3 months of systemic anticoagulation without complications. He reports no family history of clotting disorders or venous thromboembolism (VTE) and no reversible risk factors for VTE such as prolonged immobility, recent surgery, or high‐risk medications. A computed tomogram pulmonary embolism protocol shows multiple right lower lobe, segmental pulmonary emboli. Anticoagulation is initiated, and the patient is admitted to the hospital. Will inpatient inherited thrombophilia testing impact management for this case?
WHY MAY INHERITED THROMBOPHILIA TESTING PROVE HELPFUL?
The annual incidence rate of a first VTE event is estimated as 117 per 100,000 individuals per year.[1] The most common presentations are symptomatic DVT of the leg (annual incidence approximately 48 per 100,000 people), or a pulmonary embolism (annual incidence approximately 69 per 100,000 people).[1] Pulmonary embolism results in death in up to 30% of untreated patients and 2.5% of patients who receive systemic anticoagulation.[2] Principal in the pathogenesis of VTE are factors described by Virchow's triad: venous stasis, endothelial injury, and systemic hypercoagulability. By identifying a mutation in 1 or more of the factors in the clotting pathway, an evaluation for inherited thrombophilia theoretically may unearth factors that drive systemic hypercoagulability and inform decision making so as to prevent future events.
Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of VTE.[3] Approximately 7% of the general population has inherited thrombophilia, which includes factor V Leiden (FVL) mutation, prothrombin 20210 mutation (PT20210), protein C deficiency, protein S deficiency, antithrombin III (ATIII) deficiency, and methylene tetrahydrofolate reductase mutation (MTHFR).[4] Of note, the definition does not include acquired etiologies, such as antiphospholipid antibody syndrome. Depending on the underlying condition and expression of the genetic abnormality, the relative risk of VTE in patients with inherited thrombophilia is 3‐ to 20‐fold greater than that of the general population.[5] Therefore, it is logical to consider that testing for inherited thrombophilia might be clinically useful. However, the evidence for doing so is very limited.
DOES INHERITED THROMBOPHILIA TESTING CHANGE MANAGEMENT?
An inherited thrombophilia evaluation is unlikely to affect management in most clinical settings. There is no current evidence to support primary prophylaxis[6] nor is there evidence that management of patients with recurrent VTE should be altered in the setting of inherited thrombophilia.
To date, no prospective trials have evaluated the efficacy of anticoagulant use for primary prevention of VTE in patients with inherited thrombophilia.[6] Given the limited evidence for thromboprophylaxis and risks of anticoagulation, primary prevention for patients with inherited thrombophilia that remain asymptomatic is not recommended by the current American College of Chest Physicians guidelines.[7, 8]
Similarly, in patients with a first VTE or recurrent VTE, diagnosis of inherited thrombophilia is often not associated with recurrent events, which suggests that other nongenetic factors may be just as important, if not more important, in determining the risk of recurrence.[9] Although no randomized controlled or controlled clinical trials have evaluated the effects of testing for inherited thrombophilia on recurrent VTE,[10, 11] several prospective studies have assessed risk factors for recurrence. Data from these studies suggest that recurrence rates after unprovoked VTE are only weakly correlated with inherited thrombophilia status.[12, 13] Rather, it is postulated that patients with recurrent VTE may exhibit a prothrombotic tendency regardless of underlying genetic predisposition. In this case, decisions regarding anticoagulation do not vary by thrombophilia status. Instead, thrombophilia testing may divert attention away from the management of more prevalent, potentially modifiable risk factors such as immobility, oral contraceptive use, or malignancy, all of which are associated with recurrent VTE.[14] These provoking factors are the most important determinants of the chance of VTE recurrence as well as the most significant factors to take into account when deciding duration of anticoagulation.
Christiansen et al. performed a prospective study evaluating the association between recurrent VTE and thrombophilia status. After following 474 patients with confirmed first episode VTE for a mean of 7.3 years, no statistically significant risk of VTE was found for patients with FVL (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.7‐1.9), PT20210 (HR: 0.7, 95% CI: 0.3‐2.0), or an anticoagulant (protein C, protein S or ATIII) deficiency (HR: 1.8, 95% CI: 0.9‐3.7).[15] Although unexplained VTE was statistically associated with VTE recurrence, heritable thrombophilia status was not.
In a systematic review and meta‐analysis investigating the association of FVL and PT20210 with recurrent VTE, Ho and colleagues found a statistically significant risk of recurrent VTE in patients with inherited thrombophilia due to FVL (odds ratio [OR]: 1.41, 95% CI: 1.14‐1.75) and PT20210 (OR: 1.72, 95% CI: 1.27‐2.31), and reported that at most, only up to 1 in 6 recurrent VTEs may be attributable to these mutations.[16] Based on this relatively modest effect, the authors question the utility of testing for inherited thrombophilia, as thrombophilia status is unlikely to warrant a change in type or duration of treatment.
Regardless of whether an underlying inherited thrombophilia is identified, patients with history of recurrent VTE are often candidates for long‐term anticoagulation. Testing for inherited thrombophilia in patients with prior VTE events will therefore not influence decisions regarding clinical management. Additionally, such testing may be confounded by ongoing disease or treatment (Table 1). For example, protein C, protein S antigen, and ATIII levels are low in the setting of acute VTE.[17, 18] Likewise, protein C and S (vitamin Kdependent proteins) will be low in the setting of anticoagulation with warfarin.[19] Moreover, ATIII activity and antigen levels are low in the setting of heparin use.[20] Lack of provider awareness regarding these interactions may have important negative consequences, including a spurious diagnosis of thrombophilia,[21, 22] unnecessary hematology consultation, and psychological distress to patients in the form of ongoing unwarranted testing or apprehension regarding recurrence.[23]
| Acute VTE | Anticoagulation With Warfarin | Anticoagulation With NOACs | Anticoagulation With Heparin/LMWH | |
|---|---|---|---|---|
| ||||
| FVL/PT20210/MTHFR gene mutations | No Impact | No Impact | No Impact | No Impact |
| Protein C* | Decreased | Decreased | No impact | No impact |
| Protein S* | Decreased | Decreased | No impact | No impact |
| ATIII activity | Decreased | Slight increase | Slight increase | Decreased |
| ATIII antigen | Decreased | Slight increase | Slight increase | Decreased |
Additionally, this expensive evaluation has estimated direct costs of $1100 to $2400 per thrombophilia panel based on estimation of charges billed by a large commercial laboratory.[24, 25] In 2014, over 280,000 claims were submitted under Medicare Part B across all care settings for a thrombophilia analysis including FVL, PT20210, and MTHFR gene mutations,[24] which would equate to between $300 million to $672 million.[26] Unfortunately, there have been no large‐scale trials to assess cost‐effectiveness. However, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stated that cost‐effectiveness modeling studies in this area require updating with current VTE risk estimates but are suggestive that routine FVL/PT20210 testing is not cost‐effective.[27]
ARE THERE CIRCUMSTANCES IN WHICH INPATIENT INHERITED THROMBOPHILIA TESTING PROVES BENEFICIAL?
The evidence for when to test for inherited thrombophilia is very limited and is often based on individualized risk. The current EGAPP guidelines acknowledge this limitation, specifically noting that there is a paucity of data evaluating management or prophylaxis of patients with homozygous or compound heterozygous FVL or P20210 mutation, and a lack of data surrounding whether or not knowledge of thrombophilia mutation should affect anticoagulation treatment.[27] This is why an individualized approach is deemed necessary. For example, the decision to prescribe hormone replacement therapy in women with a family history of inherited thrombophilia may be better informed by testing prior to treatment. Similarly, pregnant women with a family history or personal history of VTE may also benefit from inherited thrombophilia testing, as this may influence antepartum or postpartum management.[28, 29] The National Institute for Health and Clinical Excellence (NICE) guidelines recommend consideration of testing for hereditary thrombophilia in patients with unprovoked VTE and a first‐degree relative with VTE, if stopping anticoagulation treatment is planned; however, these recommendations are based solely on Guideline Development Group's experience and opinion.[30] Regardless, testing for inherited thrombophilia has significant potential consequences. Patients at risk should meet with an outpatient hematologist and/or a genetic counselor, if available, to determine the risks and benefits of testing.
WHAT DO GUIDELINES SAY ABOUT INHERITED THROMBOPHILIA TESTING?
The most recent NICE guidelines recommend against offering inherited thrombophilia testing to patients presenting with a provoked VTE in any clinical setting.[30] In patients diagnosed with unprovoked VTE, testing should not be considered unless a first degree relative with a history of VTE exists.[30] The NICE guidelines also recommend against routinely offering thrombophilia testing to asymptomatic first‐degree relatives of patients with a history of VTE or known inherited thrombophilia. This recommendation is reflected in the American Society of Hematology's Choosing Wisely recommendations since 2013.[31] Further, The American College of Medical Genetics and Genomics' Choosing Wisely recommendations from 2015 state that MTHFR mutations should never be included in any thrombophilia workup, as recent meta‐analyses have disproven an association between the presence of these variants and venous thromboembolism.[32]
The EGAPP Working Group recommends against routine testing for FVL or PT20210 in patients who present with an idiopathic VTE, as longer‐term anticoagulation offers similar benefits to patients with or without these mutations.[27] EGAPP also recommends against testing asymptomatic adult family members of patients with VTE and/or an FVL or PT20210 mutation for the purpose of considering primary prophylactic anticoagulation. In these circumstances, it is felt that the potential risks of thrombophilia testing outweigh any potential benefits.
HOW SHOULD HOSPITALISTS APPROACH TESTING OF INHERITED THROMBOPHILIA?
The providers in our case presentation are challenged with determining whether inpatient thrombophilia evaluation will add value to the evaluation of patients with unprovoked VTE. The available evidence suggests that clinicians should avoid ordering thrombophilia testing for hospitalized patients with unprovoked VTE because (1) many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation, (2) results of testing often do not influence management, (3) testing is not cost‐effective, (4) a positive test result may lead to unnecessary patient anxiety, and (5) testing may result in inappropriately prolonged anticoagulation courses or unnecessary involvement of inpatient consultants. For these reasons, the patient in our case presentation should not be tested for inherited thrombophilia. In patients with personal or family histories of recurrent thromboembolism, modifiable clinical risk factors should be addressed, as these are more likely to influence treatment decisions compared to genetic testing. Finally, patients may be referred to an outpatient hematologist or geneticist for individualized discussions of risks and benefits of testing for inherited thrombophilia.
CONCLUSION
Inpatient evaluation for inherited thrombophilia for VTE is not clinically useful, cost‐effective, or reliable in the setting of VTE. The result of such testing does not affect management of acute primary or recurrent VTE. Testing should only be considered using an individualized approach in the outpatient setting with appropriate genetic counseling.
Disclosure: Christopher M. Petrilli, MD, and Lauren Heidemann, MD, contributed equally to this work. The authors report no conflicts of interest.
Do you think this is a low‐value practice? Is this truly a Thing We Do for No Reason? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other Things We Do for No Reason topics by emailing [email protected].
The Things We Do for No Reason (TWDFNR) series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent black and white conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/
Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of venous thromboembolism (VTE). This disorder is prevalent in approximately 7% of the population and includes mutations such as factor V Leiden, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin deficiency, and methylene tetrahydrofolate reductase. The relative risk of VTE is 3‐ to 20‐fold greater in patients with inherited thrombophilia compared with the general population. Is testing for inherited thrombophilia recommended? The available evidence suggests that testing for inherited thrombophilia is not recommended in most clinical settings. In patients without a personal history of VTE, thrombophilia results do not change management, as there is no evidence to support thromboprophylaxis in this setting. In patients with a personal history of provoked or unprovoked VTE, inpatient testing is not indicated, as results do not influence management, testing is not cost‐effective, and a positive test result may lead to unnecessary patient anxiety or may result in unnecessary involvement of consultants. Testing in hospitalized patients has even more limitations because many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation.
CASE PRESENTATION
A 23‐year‐old man presents to the emergency room with pleuritic chest pain and new oxygen requirement of 2 L nasal cannula. He has a history of unprovoked lower extremity deep venous thrombosis (DVT) diagnosed at age 20 and completed 3 months of systemic anticoagulation without complications. He reports no family history of clotting disorders or venous thromboembolism (VTE) and no reversible risk factors for VTE such as prolonged immobility, recent surgery, or high‐risk medications. A computed tomogram pulmonary embolism protocol shows multiple right lower lobe, segmental pulmonary emboli. Anticoagulation is initiated, and the patient is admitted to the hospital. Will inpatient inherited thrombophilia testing impact management for this case?
WHY MAY INHERITED THROMBOPHILIA TESTING PROVE HELPFUL?
The annual incidence rate of a first VTE event is estimated as 117 per 100,000 individuals per year.[1] The most common presentations are symptomatic DVT of the leg (annual incidence approximately 48 per 100,000 people), or a pulmonary embolism (annual incidence approximately 69 per 100,000 people).[1] Pulmonary embolism results in death in up to 30% of untreated patients and 2.5% of patients who receive systemic anticoagulation.[2] Principal in the pathogenesis of VTE are factors described by Virchow's triad: venous stasis, endothelial injury, and systemic hypercoagulability. By identifying a mutation in 1 or more of the factors in the clotting pathway, an evaluation for inherited thrombophilia theoretically may unearth factors that drive systemic hypercoagulability and inform decision making so as to prevent future events.
Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of VTE.[3] Approximately 7% of the general population has inherited thrombophilia, which includes factor V Leiden (FVL) mutation, prothrombin 20210 mutation (PT20210), protein C deficiency, protein S deficiency, antithrombin III (ATIII) deficiency, and methylene tetrahydrofolate reductase mutation (MTHFR).[4] Of note, the definition does not include acquired etiologies, such as antiphospholipid antibody syndrome. Depending on the underlying condition and expression of the genetic abnormality, the relative risk of VTE in patients with inherited thrombophilia is 3‐ to 20‐fold greater than that of the general population.[5] Therefore, it is logical to consider that testing for inherited thrombophilia might be clinically useful. However, the evidence for doing so is very limited.
DOES INHERITED THROMBOPHILIA TESTING CHANGE MANAGEMENT?
An inherited thrombophilia evaluation is unlikely to affect management in most clinical settings. There is no current evidence to support primary prophylaxis[6] nor is there evidence that management of patients with recurrent VTE should be altered in the setting of inherited thrombophilia.
To date, no prospective trials have evaluated the efficacy of anticoagulant use for primary prevention of VTE in patients with inherited thrombophilia.[6] Given the limited evidence for thromboprophylaxis and risks of anticoagulation, primary prevention for patients with inherited thrombophilia that remain asymptomatic is not recommended by the current American College of Chest Physicians guidelines.[7, 8]
Similarly, in patients with a first VTE or recurrent VTE, diagnosis of inherited thrombophilia is often not associated with recurrent events, which suggests that other nongenetic factors may be just as important, if not more important, in determining the risk of recurrence.[9] Although no randomized controlled or controlled clinical trials have evaluated the effects of testing for inherited thrombophilia on recurrent VTE,[10, 11] several prospective studies have assessed risk factors for recurrence. Data from these studies suggest that recurrence rates after unprovoked VTE are only weakly correlated with inherited thrombophilia status.[12, 13] Rather, it is postulated that patients with recurrent VTE may exhibit a prothrombotic tendency regardless of underlying genetic predisposition. In this case, decisions regarding anticoagulation do not vary by thrombophilia status. Instead, thrombophilia testing may divert attention away from the management of more prevalent, potentially modifiable risk factors such as immobility, oral contraceptive use, or malignancy, all of which are associated with recurrent VTE.[14] These provoking factors are the most important determinants of the chance of VTE recurrence as well as the most significant factors to take into account when deciding duration of anticoagulation.
Christiansen et al. performed a prospective study evaluating the association between recurrent VTE and thrombophilia status. After following 474 patients with confirmed first episode VTE for a mean of 7.3 years, no statistically significant risk of VTE was found for patients with FVL (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.7‐1.9), PT20210 (HR: 0.7, 95% CI: 0.3‐2.0), or an anticoagulant (protein C, protein S or ATIII) deficiency (HR: 1.8, 95% CI: 0.9‐3.7).[15] Although unexplained VTE was statistically associated with VTE recurrence, heritable thrombophilia status was not.
In a systematic review and meta‐analysis investigating the association of FVL and PT20210 with recurrent VTE, Ho and colleagues found a statistically significant risk of recurrent VTE in patients with inherited thrombophilia due to FVL (odds ratio [OR]: 1.41, 95% CI: 1.14‐1.75) and PT20210 (OR: 1.72, 95% CI: 1.27‐2.31), and reported that at most, only up to 1 in 6 recurrent VTEs may be attributable to these mutations.[16] Based on this relatively modest effect, the authors question the utility of testing for inherited thrombophilia, as thrombophilia status is unlikely to warrant a change in type or duration of treatment.
Regardless of whether an underlying inherited thrombophilia is identified, patients with history of recurrent VTE are often candidates for long‐term anticoagulation. Testing for inherited thrombophilia in patients with prior VTE events will therefore not influence decisions regarding clinical management. Additionally, such testing may be confounded by ongoing disease or treatment (Table 1). For example, protein C, protein S antigen, and ATIII levels are low in the setting of acute VTE.[17, 18] Likewise, protein C and S (vitamin Kdependent proteins) will be low in the setting of anticoagulation with warfarin.[19] Moreover, ATIII activity and antigen levels are low in the setting of heparin use.[20] Lack of provider awareness regarding these interactions may have important negative consequences, including a spurious diagnosis of thrombophilia,[21, 22] unnecessary hematology consultation, and psychological distress to patients in the form of ongoing unwarranted testing or apprehension regarding recurrence.[23]
| Acute VTE | Anticoagulation With Warfarin | Anticoagulation With NOACs | Anticoagulation With Heparin/LMWH | |
|---|---|---|---|---|
| ||||
| FVL/PT20210/MTHFR gene mutations | No Impact | No Impact | No Impact | No Impact |
| Protein C* | Decreased | Decreased | No impact | No impact |
| Protein S* | Decreased | Decreased | No impact | No impact |
| ATIII activity | Decreased | Slight increase | Slight increase | Decreased |
| ATIII antigen | Decreased | Slight increase | Slight increase | Decreased |
Additionally, this expensive evaluation has estimated direct costs of $1100 to $2400 per thrombophilia panel based on estimation of charges billed by a large commercial laboratory.[24, 25] In 2014, over 280,000 claims were submitted under Medicare Part B across all care settings for a thrombophilia analysis including FVL, PT20210, and MTHFR gene mutations,[24] which would equate to between $300 million to $672 million.[26] Unfortunately, there have been no large‐scale trials to assess cost‐effectiveness. However, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stated that cost‐effectiveness modeling studies in this area require updating with current VTE risk estimates but are suggestive that routine FVL/PT20210 testing is not cost‐effective.[27]
ARE THERE CIRCUMSTANCES IN WHICH INPATIENT INHERITED THROMBOPHILIA TESTING PROVES BENEFICIAL?
The evidence for when to test for inherited thrombophilia is very limited and is often based on individualized risk. The current EGAPP guidelines acknowledge this limitation, specifically noting that there is a paucity of data evaluating management or prophylaxis of patients with homozygous or compound heterozygous FVL or P20210 mutation, and a lack of data surrounding whether or not knowledge of thrombophilia mutation should affect anticoagulation treatment.[27] This is why an individualized approach is deemed necessary. For example, the decision to prescribe hormone replacement therapy in women with a family history of inherited thrombophilia may be better informed by testing prior to treatment. Similarly, pregnant women with a family history or personal history of VTE may also benefit from inherited thrombophilia testing, as this may influence antepartum or postpartum management.[28, 29] The National Institute for Health and Clinical Excellence (NICE) guidelines recommend consideration of testing for hereditary thrombophilia in patients with unprovoked VTE and a first‐degree relative with VTE, if stopping anticoagulation treatment is planned; however, these recommendations are based solely on Guideline Development Group's experience and opinion.[30] Regardless, testing for inherited thrombophilia has significant potential consequences. Patients at risk should meet with an outpatient hematologist and/or a genetic counselor, if available, to determine the risks and benefits of testing.
WHAT DO GUIDELINES SAY ABOUT INHERITED THROMBOPHILIA TESTING?
The most recent NICE guidelines recommend against offering inherited thrombophilia testing to patients presenting with a provoked VTE in any clinical setting.[30] In patients diagnosed with unprovoked VTE, testing should not be considered unless a first degree relative with a history of VTE exists.[30] The NICE guidelines also recommend against routinely offering thrombophilia testing to asymptomatic first‐degree relatives of patients with a history of VTE or known inherited thrombophilia. This recommendation is reflected in the American Society of Hematology's Choosing Wisely recommendations since 2013.[31] Further, The American College of Medical Genetics and Genomics' Choosing Wisely recommendations from 2015 state that MTHFR mutations should never be included in any thrombophilia workup, as recent meta‐analyses have disproven an association between the presence of these variants and venous thromboembolism.[32]
The EGAPP Working Group recommends against routine testing for FVL or PT20210 in patients who present with an idiopathic VTE, as longer‐term anticoagulation offers similar benefits to patients with or without these mutations.[27] EGAPP also recommends against testing asymptomatic adult family members of patients with VTE and/or an FVL or PT20210 mutation for the purpose of considering primary prophylactic anticoagulation. In these circumstances, it is felt that the potential risks of thrombophilia testing outweigh any potential benefits.
HOW SHOULD HOSPITALISTS APPROACH TESTING OF INHERITED THROMBOPHILIA?
The providers in our case presentation are challenged with determining whether inpatient thrombophilia evaluation will add value to the evaluation of patients with unprovoked VTE. The available evidence suggests that clinicians should avoid ordering thrombophilia testing for hospitalized patients with unprovoked VTE because (1) many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation, (2) results of testing often do not influence management, (3) testing is not cost‐effective, (4) a positive test result may lead to unnecessary patient anxiety, and (5) testing may result in inappropriately prolonged anticoagulation courses or unnecessary involvement of inpatient consultants. For these reasons, the patient in our case presentation should not be tested for inherited thrombophilia. In patients with personal or family histories of recurrent thromboembolism, modifiable clinical risk factors should be addressed, as these are more likely to influence treatment decisions compared to genetic testing. Finally, patients may be referred to an outpatient hematologist or geneticist for individualized discussions of risks and benefits of testing for inherited thrombophilia.
CONCLUSION
Inpatient evaluation for inherited thrombophilia for VTE is not clinically useful, cost‐effective, or reliable in the setting of VTE. The result of such testing does not affect management of acute primary or recurrent VTE. Testing should only be considered using an individualized approach in the outpatient setting with appropriate genetic counseling.
Disclosure: Christopher M. Petrilli, MD, and Lauren Heidemann, MD, contributed equally to this work. The authors report no conflicts of interest.
Do you think this is a low‐value practice? Is this truly a Thing We Do for No Reason? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other Things We Do for No Reason topics by emailing [email protected].
- , , , , , . Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25‐year population‐based study. Arch Intern Med. 1998;158(6):585–593.
- , , , et al. The clinical course of pulmonary embolism. N Engl J Med. 1992;326(19):1240–1245.
- , . Hereditary thrombophilia. Thromb J. 2006;4:15.
- , , , . Deep‐vein thrombosis. Lancet. 1999;353(9151):479–485.
- , , , et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450–2457.
- , , , et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S–e736S.
- , . Testing for inherited thrombophilia and consequences for antithrombotic prophylaxis in patients with venous thromboembolism and their relatives. A review of the Guidelines from Scientific Societies and Working Groups. Thromb Haemost. 2013;110(4):697–705.
- , , , et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S–e226S.
- , , , et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301(23):2472–2485.
- , , , . Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst Rev. 2009;(1):CD007069.
- , , , . Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst Rev. 2012;12:CD007069.
- , , , . Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362(9383):523–526.
- , , , et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood. 2008;112(12):4432–4436.
- , . Testing for thrombophilia: an evidence‐based approach. Postgrad Med J. 2006;82(973):699–704.
- , , , , . Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA. 2005;293(19):2352–2361.
- , , , . Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med. 2006;166(7):729–736.
- , , , . Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest. 1986;77(2):416–425.
- , . Inherited antithrombin deficiency: a review. Haemophilia. 2008;14(6):1229–1239.
- , , , . Decline of proteins C and S and factors II, VII, IX and X during the initiation of warfarin therapy. Thromb Res. 1987;45(6):783–790.
- . Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007:127–135.
- , , . Activated protein C resistance testing for factor V Leiden. Am J Hematol. 2014;89(12):1147–1150.
- , . Quantitation of human protein S in the plasma of normal and warfarin‐treated individuals by radioimmunoassay. Thromb Res. 1984;36(6):527–535.
- , , , . Social aspects of genetic testing for factor V Leiden mutation in healthy individuals and their importance for daily practice. Thromb Res. 2004;113(1):7–12.
- , . Hypercoagulability: clinical assessment and treatment. South Med J. 2001;94(10):1013–1020.
- , , . An evaluation of thrombophilia screening in an urban tertiary care medical center: A “real world” experience. Am J Clin Pathol. 2006;126(1):120–127.
- CodeMap. Available at: https://www.codemap.com. Accessed January 18, 2016.
- Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Genet Med. 2011;13(1):67–76.
- , , , et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group. N Engl J Med. 2000;343(20):1439–1444.
- , , , et al. Frequency of pregnancy‐related venous thromboembolism in anticoagulant factor‐deficient women: implications for prophylaxis. Ann Intern Med. 1996;125(12):955–960.
- , , , ; Guideline Development Group. Management of venous thromboembolic diseases and the role of thrombophilia testing: summary of NICE guidance. BMJ. 2012;344:e3979.
- American Society of Hematology. Ten things physicians and patients should question. Choosing Wisely website. Available at: http://www.choosingwisely.org/societies/american‐society‐of‐hematology. Published December 4, 2013. Accessed January 18, 2016.
- American College of Medical Genetics and Genomics. Five Things patients and providers should question. Choosing Wisely website. Available at: http://www.choosingwisely.org/societies/american‐college‐of‐medical‐genetics‐and‐genomics. Published July 10, 2015. Accessed March 13, 2016.
- , , , , , . Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25‐year population‐based study. Arch Intern Med. 1998;158(6):585–593.
- , , , et al. The clinical course of pulmonary embolism. N Engl J Med. 1992;326(19):1240–1245.
- , . Hereditary thrombophilia. Thromb J. 2006;4:15.
- , , , . Deep‐vein thrombosis. Lancet. 1999;353(9151):479–485.
- , , , et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8(11):2450–2457.
- , , , et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S–e736S.
- , . Testing for inherited thrombophilia and consequences for antithrombotic prophylaxis in patients with venous thromboembolism and their relatives. A review of the Guidelines from Scientific Societies and Working Groups. Thromb Haemost. 2013;110(4):697–705.
- , , , et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S–e226S.
- , , , et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301(23):2472–2485.
- , , , . Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst Rev. 2009;(1):CD007069.
- , , , . Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst Rev. 2012;12:CD007069.
- , , , . Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362(9383):523–526.
- , , , et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood. 2008;112(12):4432–4436.
- , . Testing for thrombophilia: an evidence‐based approach. Postgrad Med J. 2006;82(973):699–704.
- , , , , . Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA. 2005;293(19):2352–2361.
- , , , . Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med. 2006;166(7):729–736.
- , , , . Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest. 1986;77(2):416–425.
- , . Inherited antithrombin deficiency: a review. Haemophilia. 2008;14(6):1229–1239.
- , , , . Decline of proteins C and S and factors II, VII, IX and X during the initiation of warfarin therapy. Thromb Res. 1987;45(6):783–790.
- . Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007:127–135.
- , , . Activated protein C resistance testing for factor V Leiden. Am J Hematol. 2014;89(12):1147–1150.
- , . Quantitation of human protein S in the plasma of normal and warfarin‐treated individuals by radioimmunoassay. Thromb Res. 1984;36(6):527–535.
- , , , . Social aspects of genetic testing for factor V Leiden mutation in healthy individuals and their importance for daily practice. Thromb Res. 2004;113(1):7–12.
- , . Hypercoagulability: clinical assessment and treatment. South Med J. 2001;94(10):1013–1020.
- , , . An evaluation of thrombophilia screening in an urban tertiary care medical center: A “real world” experience. Am J Clin Pathol. 2006;126(1):120–127.
- CodeMap. Available at: https://www.codemap.com. Accessed January 18, 2016.
- Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Genet Med. 2011;13(1):67–76.
- , , , et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group. N Engl J Med. 2000;343(20):1439–1444.
- , , , et al. Frequency of pregnancy‐related venous thromboembolism in anticoagulant factor‐deficient women: implications for prophylaxis. Ann Intern Med. 1996;125(12):955–960.
- , , , ; Guideline Development Group. Management of venous thromboembolic diseases and the role of thrombophilia testing: summary of NICE guidance. BMJ. 2012;344:e3979.
- American Society of Hematology. Ten things physicians and patients should question. Choosing Wisely website. Available at: http://www.choosingwisely.org/societies/american‐society‐of‐hematology. Published December 4, 2013. Accessed January 18, 2016.
- American College of Medical Genetics and Genomics. Five Things patients and providers should question. Choosing Wisely website. Available at: http://www.choosingwisely.org/societies/american‐college‐of‐medical‐genetics‐and‐genomics. Published July 10, 2015. Accessed March 13, 2016.
© 2016 Society of Hospital Medicine
New mechanical ventilation guidelines unveiled
LOS ANGELES – Acutely hospitalized patients who have been on mechanical ventilation for more than 24 hours, are at high risk for extubation failure, and have passed a spontaneous breathing trial should be extubated to noninvasive ventilation.
The recommendation comes from new clinical practice guidelines from the American College of Chest Physicians and the American Thoracic Society. Moderate-quality evidence suggests that early extubation and a switch to noninvasive ventilation reduces ventilator-related and ICU-related complications, including infections and injury to the lungs and other organs. Extubation also cuts costs by reducing ICU stays.
At the annual meeting of the American College of Chest Physicians, one of the six project cochairs, Daniel R. Ouellette, MD, said that the guidelines were intended to address “new territory” from the evidence-based guidelines for weaning and discontinuing ventilator support that were published in 2001. That effort, chaired by Neil R. MacIntyre, MD, “was a landmark article that helped us learn about the steps that we needed to take to liberate patients from mechanical ventilation,” said Dr. Ouellette of the Henry Ford Hospital Department of Pulmonary and Critical Care Medicine, Detroit. “We hope that this guideline lives up to the importance of that one. We wanted to look over new information and give new recommendations about things that haven’t been addressed in the past.”
Six recommendations from the guideline panel include:
We suggest that the initial spontaneous breathing trial be conducted with inspiratory pressure augmentation rather than T-piece or continuous positive airway pressure. The committee wrote that conducting the initial spontaneous breathing trial with pressure augmentation was more likely to be successful, produced a higher rate of extubation success, and was associated with a trend towards lower intensive care unit mortality.
We suggest protocols attempting to minimize sedation. The committee found that sedation protocols reduced ICU length of stay. However, the protocols did not appear to decrease time on the ventilator or reduce short-term mortality. The authors could not recommend one protocol over another but said the burden of providing sedation by any of the protocols was “very low.”
We suggest protocolized rehabilitation directed toward early mobilization. The committee wrote that patients receiving the intervention spent less time on the ventilator and were more likely to be able to walk when they left the hospital. However, their mortality rate appeared unchanged. The authors noted the exercises created additional work for ICU staff that might have come at the expense of other care priorities.
We suggest managing patients with a ventilator liberation protocol. The committee said that patients managed by protocol spent on average 25 fewer hours on mechanical ventilation and were discharged from the ICU a day early. However, their mortality rate appeared unchanged.
We suggest performing a cuff leak test in patients who meet extubation criteria and are deemed at high risk for postextubation stridor. The committee suggested that the test should be used only in patients with a high risk of stridor (abnormal breathing caused by blockage of windpipe) after extubation. Although patients passing the test had lower stridor and reintubation rates, the authors wrote that a high percentage of patients who failed the test could be successfully extubated.
For patients who failed the cuff leak test but are otherwise ready for extubation, we suggest administering systemic steroids at least 4 hours before extubation. The committee said that clinical judgment should take priority over test results, and systemic steroids should be administered to these patients at least 4 hours before extubation. The authors added that the short duration of the steroid therapy was likely to improve success rates without resulting in adverse events.
In a prepared statement, Timothy Girard, MD, of the department of medicine at the University of Pittsburgh and a lead author of the guidelines said the committee hoped the guidelines would help reduce variations in practice that do not benefit patients. “We are not prescribing a specific approach to care for every patient every time,” he said. “But we are trying to summarize the available evidence in as clear and succinct a way as possible so that clinicians know how it applies to most patients.”
Dr. Ouellette disclosed that he has received a research grant from Cardeas Pharma for health care–associated pneumonia.
Daniel R. Ouellette, MD, FCCP, comments: Liberation from mechanical ventilation is one of the most important goals in taking care of critically ill patients receiving mechanical ventilation in the ICU. Patients who have a prolonged ventilator course are at risk for many complications and so physicians who work in the intensive care unit must work carefully to liberate patients from the ventilator at the earliest possible moment. That has to be done in a safe fashion so criteria to ensure that this can be done safely are important as well.
Patients often have medical illness that requires sedation, and it is often necessary to sedate patients so that they can tolerate being on mechanical ventilation; however, we know that oversedation can lead to failure to liberate patients from mechanical ventilation expeditiously. Therefore, one of our recommendations’ suggestions is to design protocols for sedation that focus on minimizing sedation so that patients can be extubated expeditiously.
All of the recommendations ultimately focused on a team approach to liberation from mechanical ventilation, because involvement of team members is always important. However, there are a couple of our recommendations that are particularly important in terms of their implications for the team approach and those include recommendations about using protocols to liberate patients from ventilators, in general, and also to use sedation protocols to minimize sedations.
We began to look at developing this topic, because we had initially published guidelines on [liberation from mechanical ventilation] in 2001. We knew that there was much new information that had emerged since the 2001 guidelines. For that reason we began to think about an update. With the initial inception of this project, we reached out to the American Thoracic Society so as to develop a collaborative effort since this was a topic that interested both societies. This collaboration was at all levels at CHEST and it involved not only the guidelines organization, but also the leadership of both societies and, of course, the panel that was ultimately constructed to address these issues was made up of members from both societies. The entire process [of developing the new guideline] took nearly 3 years.
When one develops a guideline, one makes an effort to make a guideline as comprehensive and globally applicable as possible. I think the practices in Europe are very similar to practices in North America in terms of mechanical ventilation. Several of our panelists are European and some of the important work that we reviewed came from centers in Europe. It’s my opinion that our guideline will be broadly applicable in both North America and Europe, but there may be regional or local differences. Nevertheless, we recognize in different regions in the world, there are different resource allocations for medical treatment, there are different cultural precepts, and there are other factors that implicate medical problems.
Certainly the European Respiratory Society and other European organizations developed guidelines on related topics ... one of the important caveats when CHEST decides to develop a guideline is that we are not reproducing the work that has been done elsewhere and so this guideline represents a project that fills a gap that previously had not been filled.
All guidelines that CHEST develops are living guidelines … it’s hard to envision exactly how often a guideline will be updated. We know that there will be certain areas of our guideline that will stand the test of time, but there will be other areas that will need to be updated, some sooner than others.
The original CHEST guideline on liberation from mechanical ventilation was a very important document that appeared in 2001 and changed the practice of medicine and the practice of managing patients on mechanical ventilation. Nevertheless, the guideline was somewhat limited in scope, because there was only so much information available. … Our goal in developing this guideline was to address some of practitioners’ questions that had emerged in the last decade by looking at newly available data.
[In formulating these guidelines], we purposely chose six new questions that were not directly related to any of the questions [that has been answered] in the previous guideline.
Daniel R. Ouellette, MD, FCCP, comments: Liberation from mechanical ventilation is one of the most important goals in taking care of critically ill patients receiving mechanical ventilation in the ICU. Patients who have a prolonged ventilator course are at risk for many complications and so physicians who work in the intensive care unit must work carefully to liberate patients from the ventilator at the earliest possible moment. That has to be done in a safe fashion so criteria to ensure that this can be done safely are important as well.
Patients often have medical illness that requires sedation, and it is often necessary to sedate patients so that they can tolerate being on mechanical ventilation; however, we know that oversedation can lead to failure to liberate patients from mechanical ventilation expeditiously. Therefore, one of our recommendations’ suggestions is to design protocols for sedation that focus on minimizing sedation so that patients can be extubated expeditiously.
All of the recommendations ultimately focused on a team approach to liberation from mechanical ventilation, because involvement of team members is always important. However, there are a couple of our recommendations that are particularly important in terms of their implications for the team approach and those include recommendations about using protocols to liberate patients from ventilators, in general, and also to use sedation protocols to minimize sedations.
We began to look at developing this topic, because we had initially published guidelines on [liberation from mechanical ventilation] in 2001. We knew that there was much new information that had emerged since the 2001 guidelines. For that reason we began to think about an update. With the initial inception of this project, we reached out to the American Thoracic Society so as to develop a collaborative effort since this was a topic that interested both societies. This collaboration was at all levels at CHEST and it involved not only the guidelines organization, but also the leadership of both societies and, of course, the panel that was ultimately constructed to address these issues was made up of members from both societies. The entire process [of developing the new guideline] took nearly 3 years.
When one develops a guideline, one makes an effort to make a guideline as comprehensive and globally applicable as possible. I think the practices in Europe are very similar to practices in North America in terms of mechanical ventilation. Several of our panelists are European and some of the important work that we reviewed came from centers in Europe. It’s my opinion that our guideline will be broadly applicable in both North America and Europe, but there may be regional or local differences. Nevertheless, we recognize in different regions in the world, there are different resource allocations for medical treatment, there are different cultural precepts, and there are other factors that implicate medical problems.
Certainly the European Respiratory Society and other European organizations developed guidelines on related topics ... one of the important caveats when CHEST decides to develop a guideline is that we are not reproducing the work that has been done elsewhere and so this guideline represents a project that fills a gap that previously had not been filled.
All guidelines that CHEST develops are living guidelines … it’s hard to envision exactly how often a guideline will be updated. We know that there will be certain areas of our guideline that will stand the test of time, but there will be other areas that will need to be updated, some sooner than others.
The original CHEST guideline on liberation from mechanical ventilation was a very important document that appeared in 2001 and changed the practice of medicine and the practice of managing patients on mechanical ventilation. Nevertheless, the guideline was somewhat limited in scope, because there was only so much information available. … Our goal in developing this guideline was to address some of practitioners’ questions that had emerged in the last decade by looking at newly available data.
[In formulating these guidelines], we purposely chose six new questions that were not directly related to any of the questions [that has been answered] in the previous guideline.
Daniel R. Ouellette, MD, FCCP, comments: Liberation from mechanical ventilation is one of the most important goals in taking care of critically ill patients receiving mechanical ventilation in the ICU. Patients who have a prolonged ventilator course are at risk for many complications and so physicians who work in the intensive care unit must work carefully to liberate patients from the ventilator at the earliest possible moment. That has to be done in a safe fashion so criteria to ensure that this can be done safely are important as well.
Patients often have medical illness that requires sedation, and it is often necessary to sedate patients so that they can tolerate being on mechanical ventilation; however, we know that oversedation can lead to failure to liberate patients from mechanical ventilation expeditiously. Therefore, one of our recommendations’ suggestions is to design protocols for sedation that focus on minimizing sedation so that patients can be extubated expeditiously.
All of the recommendations ultimately focused on a team approach to liberation from mechanical ventilation, because involvement of team members is always important. However, there are a couple of our recommendations that are particularly important in terms of their implications for the team approach and those include recommendations about using protocols to liberate patients from ventilators, in general, and also to use sedation protocols to minimize sedations.
We began to look at developing this topic, because we had initially published guidelines on [liberation from mechanical ventilation] in 2001. We knew that there was much new information that had emerged since the 2001 guidelines. For that reason we began to think about an update. With the initial inception of this project, we reached out to the American Thoracic Society so as to develop a collaborative effort since this was a topic that interested both societies. This collaboration was at all levels at CHEST and it involved not only the guidelines organization, but also the leadership of both societies and, of course, the panel that was ultimately constructed to address these issues was made up of members from both societies. The entire process [of developing the new guideline] took nearly 3 years.
When one develops a guideline, one makes an effort to make a guideline as comprehensive and globally applicable as possible. I think the practices in Europe are very similar to practices in North America in terms of mechanical ventilation. Several of our panelists are European and some of the important work that we reviewed came from centers in Europe. It’s my opinion that our guideline will be broadly applicable in both North America and Europe, but there may be regional or local differences. Nevertheless, we recognize in different regions in the world, there are different resource allocations for medical treatment, there are different cultural precepts, and there are other factors that implicate medical problems.
Certainly the European Respiratory Society and other European organizations developed guidelines on related topics ... one of the important caveats when CHEST decides to develop a guideline is that we are not reproducing the work that has been done elsewhere and so this guideline represents a project that fills a gap that previously had not been filled.
All guidelines that CHEST develops are living guidelines … it’s hard to envision exactly how often a guideline will be updated. We know that there will be certain areas of our guideline that will stand the test of time, but there will be other areas that will need to be updated, some sooner than others.
The original CHEST guideline on liberation from mechanical ventilation was a very important document that appeared in 2001 and changed the practice of medicine and the practice of managing patients on mechanical ventilation. Nevertheless, the guideline was somewhat limited in scope, because there was only so much information available. … Our goal in developing this guideline was to address some of practitioners’ questions that had emerged in the last decade by looking at newly available data.
[In formulating these guidelines], we purposely chose six new questions that were not directly related to any of the questions [that has been answered] in the previous guideline.
LOS ANGELES – Acutely hospitalized patients who have been on mechanical ventilation for more than 24 hours, are at high risk for extubation failure, and have passed a spontaneous breathing trial should be extubated to noninvasive ventilation.
The recommendation comes from new clinical practice guidelines from the American College of Chest Physicians and the American Thoracic Society. Moderate-quality evidence suggests that early extubation and a switch to noninvasive ventilation reduces ventilator-related and ICU-related complications, including infections and injury to the lungs and other organs. Extubation also cuts costs by reducing ICU stays.
At the annual meeting of the American College of Chest Physicians, one of the six project cochairs, Daniel R. Ouellette, MD, said that the guidelines were intended to address “new territory” from the evidence-based guidelines for weaning and discontinuing ventilator support that were published in 2001. That effort, chaired by Neil R. MacIntyre, MD, “was a landmark article that helped us learn about the steps that we needed to take to liberate patients from mechanical ventilation,” said Dr. Ouellette of the Henry Ford Hospital Department of Pulmonary and Critical Care Medicine, Detroit. “We hope that this guideline lives up to the importance of that one. We wanted to look over new information and give new recommendations about things that haven’t been addressed in the past.”
Six recommendations from the guideline panel include:
We suggest that the initial spontaneous breathing trial be conducted with inspiratory pressure augmentation rather than T-piece or continuous positive airway pressure. The committee wrote that conducting the initial spontaneous breathing trial with pressure augmentation was more likely to be successful, produced a higher rate of extubation success, and was associated with a trend towards lower intensive care unit mortality.
We suggest protocols attempting to minimize sedation. The committee found that sedation protocols reduced ICU length of stay. However, the protocols did not appear to decrease time on the ventilator or reduce short-term mortality. The authors could not recommend one protocol over another but said the burden of providing sedation by any of the protocols was “very low.”
We suggest protocolized rehabilitation directed toward early mobilization. The committee wrote that patients receiving the intervention spent less time on the ventilator and were more likely to be able to walk when they left the hospital. However, their mortality rate appeared unchanged. The authors noted the exercises created additional work for ICU staff that might have come at the expense of other care priorities.
We suggest managing patients with a ventilator liberation protocol. The committee said that patients managed by protocol spent on average 25 fewer hours on mechanical ventilation and were discharged from the ICU a day early. However, their mortality rate appeared unchanged.
We suggest performing a cuff leak test in patients who meet extubation criteria and are deemed at high risk for postextubation stridor. The committee suggested that the test should be used only in patients with a high risk of stridor (abnormal breathing caused by blockage of windpipe) after extubation. Although patients passing the test had lower stridor and reintubation rates, the authors wrote that a high percentage of patients who failed the test could be successfully extubated.
For patients who failed the cuff leak test but are otherwise ready for extubation, we suggest administering systemic steroids at least 4 hours before extubation. The committee said that clinical judgment should take priority over test results, and systemic steroids should be administered to these patients at least 4 hours before extubation. The authors added that the short duration of the steroid therapy was likely to improve success rates without resulting in adverse events.
In a prepared statement, Timothy Girard, MD, of the department of medicine at the University of Pittsburgh and a lead author of the guidelines said the committee hoped the guidelines would help reduce variations in practice that do not benefit patients. “We are not prescribing a specific approach to care for every patient every time,” he said. “But we are trying to summarize the available evidence in as clear and succinct a way as possible so that clinicians know how it applies to most patients.”
Dr. Ouellette disclosed that he has received a research grant from Cardeas Pharma for health care–associated pneumonia.
LOS ANGELES – Acutely hospitalized patients who have been on mechanical ventilation for more than 24 hours, are at high risk for extubation failure, and have passed a spontaneous breathing trial should be extubated to noninvasive ventilation.
The recommendation comes from new clinical practice guidelines from the American College of Chest Physicians and the American Thoracic Society. Moderate-quality evidence suggests that early extubation and a switch to noninvasive ventilation reduces ventilator-related and ICU-related complications, including infections and injury to the lungs and other organs. Extubation also cuts costs by reducing ICU stays.
At the annual meeting of the American College of Chest Physicians, one of the six project cochairs, Daniel R. Ouellette, MD, said that the guidelines were intended to address “new territory” from the evidence-based guidelines for weaning and discontinuing ventilator support that were published in 2001. That effort, chaired by Neil R. MacIntyre, MD, “was a landmark article that helped us learn about the steps that we needed to take to liberate patients from mechanical ventilation,” said Dr. Ouellette of the Henry Ford Hospital Department of Pulmonary and Critical Care Medicine, Detroit. “We hope that this guideline lives up to the importance of that one. We wanted to look over new information and give new recommendations about things that haven’t been addressed in the past.”
Six recommendations from the guideline panel include:
We suggest that the initial spontaneous breathing trial be conducted with inspiratory pressure augmentation rather than T-piece or continuous positive airway pressure. The committee wrote that conducting the initial spontaneous breathing trial with pressure augmentation was more likely to be successful, produced a higher rate of extubation success, and was associated with a trend towards lower intensive care unit mortality.
We suggest protocols attempting to minimize sedation. The committee found that sedation protocols reduced ICU length of stay. However, the protocols did not appear to decrease time on the ventilator or reduce short-term mortality. The authors could not recommend one protocol over another but said the burden of providing sedation by any of the protocols was “very low.”
We suggest protocolized rehabilitation directed toward early mobilization. The committee wrote that patients receiving the intervention spent less time on the ventilator and were more likely to be able to walk when they left the hospital. However, their mortality rate appeared unchanged. The authors noted the exercises created additional work for ICU staff that might have come at the expense of other care priorities.
We suggest managing patients with a ventilator liberation protocol. The committee said that patients managed by protocol spent on average 25 fewer hours on mechanical ventilation and were discharged from the ICU a day early. However, their mortality rate appeared unchanged.
We suggest performing a cuff leak test in patients who meet extubation criteria and are deemed at high risk for postextubation stridor. The committee suggested that the test should be used only in patients with a high risk of stridor (abnormal breathing caused by blockage of windpipe) after extubation. Although patients passing the test had lower stridor and reintubation rates, the authors wrote that a high percentage of patients who failed the test could be successfully extubated.
For patients who failed the cuff leak test but are otherwise ready for extubation, we suggest administering systemic steroids at least 4 hours before extubation. The committee said that clinical judgment should take priority over test results, and systemic steroids should be administered to these patients at least 4 hours before extubation. The authors added that the short duration of the steroid therapy was likely to improve success rates without resulting in adverse events.
In a prepared statement, Timothy Girard, MD, of the department of medicine at the University of Pittsburgh and a lead author of the guidelines said the committee hoped the guidelines would help reduce variations in practice that do not benefit patients. “We are not prescribing a specific approach to care for every patient every time,” he said. “But we are trying to summarize the available evidence in as clear and succinct a way as possible so that clinicians know how it applies to most patients.”
Dr. Ouellette disclosed that he has received a research grant from Cardeas Pharma for health care–associated pneumonia.
AT CHEST 2016