PAs are highly educated, trusted health care providers who lead patient-centered medical teams. Trained as experts in general medicine, we often pursue multiple specialties over the course of our careers—typically in three or four. PAs can decide to work in surgery, emergency care, orthopedics, oncology, pediatrics, dermatology, and many other areas. Moving among and between specialties is a hallmark of our profession. Unfortunately, a new proposal would alter how PAs are tested in order to maintain their certification—and, in 20 states, potentially jeopardize their license to practice.

The National Commission on Certification of PAs (NCCPA) has proposed significant changes to how PAs are recertified by requiring multiple exams, including a proctored, closed-book exam in a specialty area and two or three take-home exams during every 10-year recertification cycle. The proposal would in effect force PAs to choose a specialty and as a result undermine their ability to fill care gaps in hospitals, health systems, and communities.

The new requirements are cumbersome and unnecessary. PAs already undergo rigorous medical training and have initial licensing requirements that are similar to those of our physician, nurse practitioner, and pharmacist colleagues—none of whom are required to retest. PAs must graduate from an accredited program and take a test in general medicine in order to be licensed and certified in the first place. Throughout their careers, they have to complete extensive continuing medical education (CME). They also practice in clinical settings that continually inform and enhance their experience and base of knowledge.

Additional testing would take valuable time away from patients and could even discourage PAs from staying in a profession that is in high demand. More to the point, NCCPA has pursued its proposal even though studies have shown that recertification testing is not related to improvements in patient outcomes or safety.

AAPA recently received a message from longtime PA Peter Schuman, who is as passionate about patient care as he is leery of NCCPA’s recertification plan. “[NCCPA has] no significant, scientifically valid evidence to support their claims. I can honestly say that their testing requirements have not helped me care for patients better or become more knowledgeable in my field of practice/expertise one bit,” he wrote. “The PANRE is a waste of time and effort and is a source of great stress, taking time away from my patients, practice, and family. Enough is enough, NCCPA!”

The AAPA board has reached out to NCCPA and still hopes that it will engage in substantive discussions. Given the seriousness of our concerns, however, the AAPA Board voted recently to take steps toward the creation of an alternative certifying body for PAs. This vote came after careful deliberation and in response to the concerns of the thousands of professionals that AAPA represents. The decision was not made lightly and it reflects the priority of PAs to put patient care ahead of unnecessary testing.

AAPA is not alone in its opposition to recertification testing. A growing number of medical associations, including the American Medical Association (AMA), reject it as unnecessary and overly burdensome. AMA has rightly identified these exams as high-stakes tests because, it said, “failure to pass can result in a physician’s loss of privileges or employment.” Every PA would face similar consequences and, in 20 states, put their license at risk. At least 19 state medical associations have adopted similar resolutions in opposition to unnecessary retesting.

To be clear, AAPA does not oppose initial testing for certification and licensing and embraces the value of an exam in the licensing process. AAPA also strongly supports extensive CME and the benefits it provides.

We have not yet decided whether to establish a new certification organization. But we do know that there is no reason PAs should be singled out for additional testing when the extra requirement does not help patients and when other medical professionals are not required to do the same. Let PAs focus on patient care, not unwarranted test-taking. 

PAs are highly educated, trusted health care providers who lead patient-centered medical teams. Trained as experts in general medicine, we often pursue multiple specialties over the course of our careers—typically in three or four. PAs can decide to work in surgery, emergency care, orthopedics, oncology, pediatrics, dermatology, and many other areas. Moving among and between specialties is a hallmark of our profession. Unfortunately, a new proposal would alter how PAs are tested in order to maintain their certification—and, in 20 states, potentially jeopardize their license to practice.

The National Commission on Certification of PAs (NCCPA) has proposed significant changes to how PAs are recertified by requiring multiple exams, including a proctored, closed-book exam in a specialty area and two or three take-home exams during every 10-year recertification cycle. The proposal would in effect force PAs to choose a specialty and as a result undermine their ability to fill care gaps in hospitals, health systems, and communities.

The new requirements are cumbersome and unnecessary. PAs already undergo rigorous medical training and have initial licensing requirements that are similar to those of our physician, nurse practitioner, and pharmacist colleagues—none of whom are required to retest. PAs must graduate from an accredited program and take a test in general medicine in order to be licensed and certified in the first place. Throughout their careers, they have to complete extensive continuing medical education (CME). They also practice in clinical settings that continually inform and enhance their experience and base of knowledge.

Additional testing would take valuable time away from patients and could even discourage PAs from staying in a profession that is in high demand. More to the point, NCCPA has pursued its proposal even though studies have shown that recertification testing is not related to improvements in patient outcomes or safety.

AAPA recently received a message from longtime PA Peter Schuman, who is as passionate about patient care as he is leery of NCCPA’s recertification plan. “[NCCPA has] no significant, scientifically valid evidence to support their claims. I can honestly say that their testing requirements have not helped me care for patients better or become more knowledgeable in my field of practice/expertise one bit,” he wrote. “The PANRE is a waste of time and effort and is a source of great stress, taking time away from my patients, practice, and family. Enough is enough, NCCPA!”

The AAPA board has reached out to NCCPA and still hopes that it will engage in substantive discussions. Given the seriousness of our concerns, however, the AAPA Board voted recently to take steps toward the creation of an alternative certifying body for PAs. This vote came after careful deliberation and in response to the concerns of the thousands of professionals that AAPA represents. The decision was not made lightly and it reflects the priority of PAs to put patient care ahead of unnecessary testing.

AAPA is not alone in its opposition to recertification testing. A growing number of medical associations, including the American Medical Association (AMA), reject it as unnecessary and overly burdensome. AMA has rightly identified these exams as high-stakes tests because, it said, “failure to pass can result in a physician’s loss of privileges or employment.” Every PA would face similar consequences and, in 20 states, put their license at risk. At least 19 state medical associations have adopted similar resolutions in opposition to unnecessary retesting.

To be clear, AAPA does not oppose initial testing for certification and licensing and embraces the value of an exam in the licensing process. AAPA also strongly supports extensive CME and the benefits it provides.

We have not yet decided whether to establish a new certification organization. But we do know that there is no reason PAs should be singled out for additional testing when the extra requirement does not help patients and when other medical professionals are not required to do the same. Let PAs focus on patient care, not unwarranted test-taking. 

PAs are highly educated, trusted health care providers who lead patient-centered medical teams. Trained as experts in general medicine, we often pursue multiple specialties over the course of our careers—typically in three or four. PAs can decide to work in surgery, emergency care, orthopedics, oncology, pediatrics, dermatology, and many other areas. Moving among and between specialties is a hallmark of our profession. Unfortunately, a new proposal would alter how PAs are tested in order to maintain their certification—and, in 20 states, potentially jeopardize their license to practice.

The National Commission on Certification of PAs (NCCPA) has proposed significant changes to how PAs are recertified by requiring multiple exams, including a proctored, closed-book exam in a specialty area and two or three take-home exams during every 10-year recertification cycle. The proposal would in effect force PAs to choose a specialty and as a result undermine their ability to fill care gaps in hospitals, health systems, and communities.

The new requirements are cumbersome and unnecessary. PAs already undergo rigorous medical training and have initial licensing requirements that are similar to those of our physician, nurse practitioner, and pharmacist colleagues—none of whom are required to retest. PAs must graduate from an accredited program and take a test in general medicine in order to be licensed and certified in the first place. Throughout their careers, they have to complete extensive continuing medical education (CME). They also practice in clinical settings that continually inform and enhance their experience and base of knowledge.

Additional testing would take valuable time away from patients and could even discourage PAs from staying in a profession that is in high demand. More to the point, NCCPA has pursued its proposal even though studies have shown that recertification testing is not related to improvements in patient outcomes or safety.

AAPA recently received a message from longtime PA Peter Schuman, who is as passionate about patient care as he is leery of NCCPA’s recertification plan. “[NCCPA has] no significant, scientifically valid evidence to support their claims. I can honestly say that their testing requirements have not helped me care for patients better or become more knowledgeable in my field of practice/expertise one bit,” he wrote. “The PANRE is a waste of time and effort and is a source of great stress, taking time away from my patients, practice, and family. Enough is enough, NCCPA!”

The AAPA board has reached out to NCCPA and still hopes that it will engage in substantive discussions. Given the seriousness of our concerns, however, the AAPA Board voted recently to take steps toward the creation of an alternative certifying body for PAs. This vote came after careful deliberation and in response to the concerns of the thousands of professionals that AAPA represents. The decision was not made lightly and it reflects the priority of PAs to put patient care ahead of unnecessary testing.

AAPA is not alone in its opposition to recertification testing. A growing number of medical associations, including the American Medical Association (AMA), reject it as unnecessary and overly burdensome. AMA has rightly identified these exams as high-stakes tests because, it said, “failure to pass can result in a physician’s loss of privileges or employment.” Every PA would face similar consequences and, in 20 states, put their license at risk. At least 19 state medical associations have adopted similar resolutions in opposition to unnecessary retesting.

To be clear, AAPA does not oppose initial testing for certification and licensing and embraces the value of an exam in the licensing process. AAPA also strongly supports extensive CME and the benefits it provides.

We have not yet decided whether to establish a new certification organization. But we do know that there is no reason PAs should be singled out for additional testing when the extra requirement does not help patients and when other medical professionals are not required to do the same. Let PAs focus on patient care, not unwarranted test-taking. 

Rivaroxaban tablets

ROME—Preliminary results from the ANNEXA-4 study suggest that andexanet alfa, an investigational antidote to factor Xa inhibitors, can be effective in patients with acute major bleeding.

The drug reversed the anticoagulant effects of rivaroxaban, apixaban, and enoxaparin in this study, providing “excellent” or “good” hemostatic efficacy in 79% of patients over 12 hours.

Thrombotic events occurred in 18% of patients, and 15% died during the 30-day follow-up period.

According to investigators, these events occurred within the range expected in this patient population, given the severity of their bleeding, their underlying thrombotic risk, and the low percentage of patients who restarted anticoagulant therapy following their bleeding episode.

Stuart J. Connolly, MD, of McMaster University in Hamilton, Ontario, Canada, presented results from  ANNEXA-4 at ESC Congress 2016 (abstract 5718).

Results were also published in NEJM. The study was funded by Portola Pharmaceuticals Inc.

Patients and treatment

The preliminary analysis of the phase 3/4 ANNEXA-4 trial included 67 patients. All of these patients were evaluated for safety, and 47 were evaluated for efficacy. The mean age of both populations was 77.1, and slightly more than half of the patients were male.

All patients received andexanet alfa given as a bolus dose over 30 minutes, followed by a 2-hour infusion. Patients received a low or high dose depending on which factor Xa inhibitor they received and the time they received it. The patients were evaluated for 30 days following andexanet alfa administration.

The co-primary efficacy endpoints are the percent change in anti-factor Xa activity at 2 hours and the assessment of hemostasis over 12 hours following the infusion. Hemostatic efficacy is assessed by an independent endpoint adjudication committee as excellent, good, or poor/none.

Efficacy

“In this preliminary analysis, [andexanet alfa] was effective in rapidly reversing anti-factor Xa inhibitor activity and restoring normal blood clotting in real-world patients with factor Xa inhibitor-related bleeding,” Dr Connolly said.

Of the 47 patients evaluable for efficacy, 32 were receiving an anticoagulant due to atrial fibrillation, 12 had venous thromboembolism (VTE), and 3 had both atrial fibrillation and VTE.

Twenty-six patients were receiving rivaroxaban, 20 were receiving apixaban, and 1 was receiving enoxaparin. Twenty-five patients had gastrointestinal bleeding, 20 had intracranial bleeding, and 2 had bleeding at other sites.

Forty-two patients received a low dose of andexanet alfa, and 5 received a high dose. The mean time from presentation to the emergency department and the administration of the andexanet alfa bolus was 4.8 ± 1.8 hours.

After the bolus, the median anti-factor Xa activity decreased by 89% from baseline among patients receiving rivaroxaban and by 93% among those receiving apixaban. At the end of the 2-hour infusion, the decrease from baseline was 86% and 92%, respectively.

Twelve hours after the infusion ended, the median anti-factor Xa activity had decreased 64% from baseline among patients receiving rivaroxaban and 31% among those receiving apixaban.

Overall, at 12 hours, clinical hemostasis was rated excellent or good in 79% of patients. Hemostatic efficacy was rated as excellent or good in 81% of the patients on rivaroxaban, 75% of the patients on apixaban, and in the 1 patient on edoxaban.

Safety

Of the 67 patients in the safety population, 47 were receiving an anticoagulant due to atrial fibrillation, 15 had VTE, and 5 had both atrial fibrillation and VTE.

Thirty-two patients were receiving rivaroxaban, 31 were receiving apixaban, and 4 were receiving edoxaban. Thirty-eight patients had gastrointestinal bleeding, 28 had intracranial bleeding, and 6 had bleeding at other sites.

There were no infusion reactions, no antibodies to factors Xa or X, and no neutralizing antibodies to andexanet alfa.

Twelve patients (18%) experienced thrombotic events—1 with myocardial infarction, 5 with stroke, 7 with deep-vein thrombosis, and 1 with pulmonary embolism. (Some patients had more than 1 event.)

“This rate of events is not unexpected, considering the thrombotic potential of the patients and the fact that, in most of them, anticoagulation was discontinued at the time of bleeding and not restarted,” Dr Connolly said.

Four patients had a thrombotic event within 3 days of andexanet alfa treatment, and the rest occurred between 4 days and 30 days.

Eighteen patients (27%) resumed anticoagulant therapy within 30 days. One of the 12 patients with a thrombotic event restarted anticoagulation at a therapeutic dose before the event. One other patient received prophylactic doses of enoxaparin before developing a deep-vein thrombosis.

There were 10 deaths (15%), 6 due to cardiovascular events.

Andexanet alfa development

Andexanet alfa is being developed as a reversal agent for apixaban, rivaroxaban, edoxaban, and enoxaparin. Andexanet alfa is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

The drug is under review by the US Food and Drug Administration (FDA) and the European Medicines Agency. The FDA recently issued a complete response letter regarding the biologics license application for andexanet alfa.

Portola said it plans to meet with the FDA as soon as possible to resolve the outstanding questions in the letter and determine the appropriate next steps.

Rivaroxaban tablets

ROME—Preliminary results from the ANNEXA-4 study suggest that andexanet alfa, an investigational antidote to factor Xa inhibitors, can be effective in patients with acute major bleeding.

The drug reversed the anticoagulant effects of rivaroxaban, apixaban, and enoxaparin in this study, providing “excellent” or “good” hemostatic efficacy in 79% of patients over 12 hours.

Thrombotic events occurred in 18% of patients, and 15% died during the 30-day follow-up period.

According to investigators, these events occurred within the range expected in this patient population, given the severity of their bleeding, their underlying thrombotic risk, and the low percentage of patients who restarted anticoagulant therapy following their bleeding episode.

Stuart J. Connolly, MD, of McMaster University in Hamilton, Ontario, Canada, presented results from  ANNEXA-4 at ESC Congress 2016 (abstract 5718).

Results were also published in NEJM. The study was funded by Portola Pharmaceuticals Inc.

Patients and treatment

The preliminary analysis of the phase 3/4 ANNEXA-4 trial included 67 patients. All of these patients were evaluated for safety, and 47 were evaluated for efficacy. The mean age of both populations was 77.1, and slightly more than half of the patients were male.

All patients received andexanet alfa given as a bolus dose over 30 minutes, followed by a 2-hour infusion. Patients received a low or high dose depending on which factor Xa inhibitor they received and the time they received it. The patients were evaluated for 30 days following andexanet alfa administration.

The co-primary efficacy endpoints are the percent change in anti-factor Xa activity at 2 hours and the assessment of hemostasis over 12 hours following the infusion. Hemostatic efficacy is assessed by an independent endpoint adjudication committee as excellent, good, or poor/none.

Efficacy

“In this preliminary analysis, [andexanet alfa] was effective in rapidly reversing anti-factor Xa inhibitor activity and restoring normal blood clotting in real-world patients with factor Xa inhibitor-related bleeding,” Dr Connolly said.

Of the 47 patients evaluable for efficacy, 32 were receiving an anticoagulant due to atrial fibrillation, 12 had venous thromboembolism (VTE), and 3 had both atrial fibrillation and VTE.

Twenty-six patients were receiving rivaroxaban, 20 were receiving apixaban, and 1 was receiving enoxaparin. Twenty-five patients had gastrointestinal bleeding, 20 had intracranial bleeding, and 2 had bleeding at other sites.

Forty-two patients received a low dose of andexanet alfa, and 5 received a high dose. The mean time from presentation to the emergency department and the administration of the andexanet alfa bolus was 4.8 ± 1.8 hours.

After the bolus, the median anti-factor Xa activity decreased by 89% from baseline among patients receiving rivaroxaban and by 93% among those receiving apixaban. At the end of the 2-hour infusion, the decrease from baseline was 86% and 92%, respectively.

Twelve hours after the infusion ended, the median anti-factor Xa activity had decreased 64% from baseline among patients receiving rivaroxaban and 31% among those receiving apixaban.

Overall, at 12 hours, clinical hemostasis was rated excellent or good in 79% of patients. Hemostatic efficacy was rated as excellent or good in 81% of the patients on rivaroxaban, 75% of the patients on apixaban, and in the 1 patient on edoxaban.

Safety

Of the 67 patients in the safety population, 47 were receiving an anticoagulant due to atrial fibrillation, 15 had VTE, and 5 had both atrial fibrillation and VTE.

Thirty-two patients were receiving rivaroxaban, 31 were receiving apixaban, and 4 were receiving edoxaban. Thirty-eight patients had gastrointestinal bleeding, 28 had intracranial bleeding, and 6 had bleeding at other sites.

There were no infusion reactions, no antibodies to factors Xa or X, and no neutralizing antibodies to andexanet alfa.

Twelve patients (18%) experienced thrombotic events—1 with myocardial infarction, 5 with stroke, 7 with deep-vein thrombosis, and 1 with pulmonary embolism. (Some patients had more than 1 event.)

“This rate of events is not unexpected, considering the thrombotic potential of the patients and the fact that, in most of them, anticoagulation was discontinued at the time of bleeding and not restarted,” Dr Connolly said.

Four patients had a thrombotic event within 3 days of andexanet alfa treatment, and the rest occurred between 4 days and 30 days.

Eighteen patients (27%) resumed anticoagulant therapy within 30 days. One of the 12 patients with a thrombotic event restarted anticoagulation at a therapeutic dose before the event. One other patient received prophylactic doses of enoxaparin before developing a deep-vein thrombosis.

There were 10 deaths (15%), 6 due to cardiovascular events.

Andexanet alfa development

Andexanet alfa is being developed as a reversal agent for apixaban, rivaroxaban, edoxaban, and enoxaparin. Andexanet alfa is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

The drug is under review by the US Food and Drug Administration (FDA) and the European Medicines Agency. The FDA recently issued a complete response letter regarding the biologics license application for andexanet alfa.

Portola said it plans to meet with the FDA as soon as possible to resolve the outstanding questions in the letter and determine the appropriate next steps.

Rivaroxaban tablets

ROME—Preliminary results from the ANNEXA-4 study suggest that andexanet alfa, an investigational antidote to factor Xa inhibitors, can be effective in patients with acute major bleeding.

The drug reversed the anticoagulant effects of rivaroxaban, apixaban, and enoxaparin in this study, providing “excellent” or “good” hemostatic efficacy in 79% of patients over 12 hours.

Thrombotic events occurred in 18% of patients, and 15% died during the 30-day follow-up period.

According to investigators, these events occurred within the range expected in this patient population, given the severity of their bleeding, their underlying thrombotic risk, and the low percentage of patients who restarted anticoagulant therapy following their bleeding episode.

Stuart J. Connolly, MD, of McMaster University in Hamilton, Ontario, Canada, presented results from  ANNEXA-4 at ESC Congress 2016 (abstract 5718).

Results were also published in NEJM. The study was funded by Portola Pharmaceuticals Inc.

Patients and treatment

The preliminary analysis of the phase 3/4 ANNEXA-4 trial included 67 patients. All of these patients were evaluated for safety, and 47 were evaluated for efficacy. The mean age of both populations was 77.1, and slightly more than half of the patients were male.

All patients received andexanet alfa given as a bolus dose over 30 minutes, followed by a 2-hour infusion. Patients received a low or high dose depending on which factor Xa inhibitor they received and the time they received it. The patients were evaluated for 30 days following andexanet alfa administration.

The co-primary efficacy endpoints are the percent change in anti-factor Xa activity at 2 hours and the assessment of hemostasis over 12 hours following the infusion. Hemostatic efficacy is assessed by an independent endpoint adjudication committee as excellent, good, or poor/none.

Efficacy

“In this preliminary analysis, [andexanet alfa] was effective in rapidly reversing anti-factor Xa inhibitor activity and restoring normal blood clotting in real-world patients with factor Xa inhibitor-related bleeding,” Dr Connolly said.

Of the 47 patients evaluable for efficacy, 32 were receiving an anticoagulant due to atrial fibrillation, 12 had venous thromboembolism (VTE), and 3 had both atrial fibrillation and VTE.

Twenty-six patients were receiving rivaroxaban, 20 were receiving apixaban, and 1 was receiving enoxaparin. Twenty-five patients had gastrointestinal bleeding, 20 had intracranial bleeding, and 2 had bleeding at other sites.

Forty-two patients received a low dose of andexanet alfa, and 5 received a high dose. The mean time from presentation to the emergency department and the administration of the andexanet alfa bolus was 4.8 ± 1.8 hours.

After the bolus, the median anti-factor Xa activity decreased by 89% from baseline among patients receiving rivaroxaban and by 93% among those receiving apixaban. At the end of the 2-hour infusion, the decrease from baseline was 86% and 92%, respectively.

Twelve hours after the infusion ended, the median anti-factor Xa activity had decreased 64% from baseline among patients receiving rivaroxaban and 31% among those receiving apixaban.

Overall, at 12 hours, clinical hemostasis was rated excellent or good in 79% of patients. Hemostatic efficacy was rated as excellent or good in 81% of the patients on rivaroxaban, 75% of the patients on apixaban, and in the 1 patient on edoxaban.

Safety

Of the 67 patients in the safety population, 47 were receiving an anticoagulant due to atrial fibrillation, 15 had VTE, and 5 had both atrial fibrillation and VTE.

Thirty-two patients were receiving rivaroxaban, 31 were receiving apixaban, and 4 were receiving edoxaban. Thirty-eight patients had gastrointestinal bleeding, 28 had intracranial bleeding, and 6 had bleeding at other sites.

There were no infusion reactions, no antibodies to factors Xa or X, and no neutralizing antibodies to andexanet alfa.

Twelve patients (18%) experienced thrombotic events—1 with myocardial infarction, 5 with stroke, 7 with deep-vein thrombosis, and 1 with pulmonary embolism. (Some patients had more than 1 event.)

“This rate of events is not unexpected, considering the thrombotic potential of the patients and the fact that, in most of them, anticoagulation was discontinued at the time of bleeding and not restarted,” Dr Connolly said.

Four patients had a thrombotic event within 3 days of andexanet alfa treatment, and the rest occurred between 4 days and 30 days.

Eighteen patients (27%) resumed anticoagulant therapy within 30 days. One of the 12 patients with a thrombotic event restarted anticoagulation at a therapeutic dose before the event. One other patient received prophylactic doses of enoxaparin before developing a deep-vein thrombosis.

There were 10 deaths (15%), 6 due to cardiovascular events.

Andexanet alfa development

Andexanet alfa is being developed as a reversal agent for apixaban, rivaroxaban, edoxaban, and enoxaparin. Andexanet alfa is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

The drug is under review by the US Food and Drug Administration (FDA) and the European Medicines Agency. The FDA recently issued a complete response letter regarding the biologics license application for andexanet alfa.

Portola said it plans to meet with the FDA as soon as possible to resolve the outstanding questions in the letter and determine the appropriate next steps.

Ticagrelor tablets

Photo courtesy of AstraZeneca

ROME—The antiplatelet drugs prasugrel and ticagrelor produce similar early results in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), according to PRAGUE-18, the first randomized, head-to-head comparison of the drugs.

“Our findings confirm previous indirect—non-randomized—comparisons of these 2 drugs, based on analyses of various registries,” said study investigator Petr Widimsky MD, DSc, of Charles University in Prague, Czech Republic.

“Thus, both drugs are very effective and safe and significantly contribute to the excellent outcomes of patients with acute myocardial infarction in modern cardiology.”

Dr Widimsky presented results from PRAGUE-18 at ESC Congress 2016 (abstract 5028). This was an investigator-initiated study, so there was no industry support.

The trial included 1230 AMI patients who were randomized to receive prasugrel (n=634) or ticagrelor (n=596) prior to PCI. There were no significant differences in baseline characteristics between the treatment arms.

Randomization took place immediately after a patient’s arrival to the PCI center. Patients received prasugrel at 60 mg, followed by 10 mg per day (5 mg per day if they were older than 75 or weighed less than 60 kg) for 1 year. Patients received ticagrelor at 180 mg, followed by 90 mg twice a day for 1 year.

The study’s primary endpoint was the occurrence of death, re-infarction, urgent target vessel revascularization, stroke, prolonged hospitalization, or serious bleeding requiring transfusion at 7 days (or discharge if earlier).

The trial was halted prematurely, after an interim analysis showed no significant difference in the rate of the primary endpoint between the prasugrel and ticagrelor arms—4.0% and 4.1%, respectively (odds ratio=0.98, P=0.939).

Likewise, there was no significant difference between the treatment arms for any of the components of the primary endpoint.

The key secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke within 30 days. There was no significant difference in the rate of this endpoint between the prasugrel and ticagrelor arms—2.7% and 2.5%, respectively (odds ratio=1.06, P=0.864).

“This study did not show any difference between ticagrelor and prasugrel in the early phase of acute myocardial infarction treated by primary PCI,” Dr Widimsky concluded.

He and his colleagues are planning the final follow-up of this study at 1 year, which will be completed in 2017.

Ticagrelor tablets

Photo courtesy of AstraZeneca

ROME—The antiplatelet drugs prasugrel and ticagrelor produce similar early results in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), according to PRAGUE-18, the first randomized, head-to-head comparison of the drugs.

“Our findings confirm previous indirect—non-randomized—comparisons of these 2 drugs, based on analyses of various registries,” said study investigator Petr Widimsky MD, DSc, of Charles University in Prague, Czech Republic.

“Thus, both drugs are very effective and safe and significantly contribute to the excellent outcomes of patients with acute myocardial infarction in modern cardiology.”

Dr Widimsky presented results from PRAGUE-18 at ESC Congress 2016 (abstract 5028). This was an investigator-initiated study, so there was no industry support.

The trial included 1230 AMI patients who were randomized to receive prasugrel (n=634) or ticagrelor (n=596) prior to PCI. There were no significant differences in baseline characteristics between the treatment arms.

Randomization took place immediately after a patient’s arrival to the PCI center. Patients received prasugrel at 60 mg, followed by 10 mg per day (5 mg per day if they were older than 75 or weighed less than 60 kg) for 1 year. Patients received ticagrelor at 180 mg, followed by 90 mg twice a day for 1 year.

The study’s primary endpoint was the occurrence of death, re-infarction, urgent target vessel revascularization, stroke, prolonged hospitalization, or serious bleeding requiring transfusion at 7 days (or discharge if earlier).

The trial was halted prematurely, after an interim analysis showed no significant difference in the rate of the primary endpoint between the prasugrel and ticagrelor arms—4.0% and 4.1%, respectively (odds ratio=0.98, P=0.939).

Likewise, there was no significant difference between the treatment arms for any of the components of the primary endpoint.

The key secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke within 30 days. There was no significant difference in the rate of this endpoint between the prasugrel and ticagrelor arms—2.7% and 2.5%, respectively (odds ratio=1.06, P=0.864).

“This study did not show any difference between ticagrelor and prasugrel in the early phase of acute myocardial infarction treated by primary PCI,” Dr Widimsky concluded.

He and his colleagues are planning the final follow-up of this study at 1 year, which will be completed in 2017.

Ticagrelor tablets

Photo courtesy of AstraZeneca

ROME—The antiplatelet drugs prasugrel and ticagrelor produce similar early results in patients with acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI), according to PRAGUE-18, the first randomized, head-to-head comparison of the drugs.

“Our findings confirm previous indirect—non-randomized—comparisons of these 2 drugs, based on analyses of various registries,” said study investigator Petr Widimsky MD, DSc, of Charles University in Prague, Czech Republic.

“Thus, both drugs are very effective and safe and significantly contribute to the excellent outcomes of patients with acute myocardial infarction in modern cardiology.”

Dr Widimsky presented results from PRAGUE-18 at ESC Congress 2016 (abstract 5028). This was an investigator-initiated study, so there was no industry support.

The trial included 1230 AMI patients who were randomized to receive prasugrel (n=634) or ticagrelor (n=596) prior to PCI. There were no significant differences in baseline characteristics between the treatment arms.

Randomization took place immediately after a patient’s arrival to the PCI center. Patients received prasugrel at 60 mg, followed by 10 mg per day (5 mg per day if they were older than 75 or weighed less than 60 kg) for 1 year. Patients received ticagrelor at 180 mg, followed by 90 mg twice a day for 1 year.

The study’s primary endpoint was the occurrence of death, re-infarction, urgent target vessel revascularization, stroke, prolonged hospitalization, or serious bleeding requiring transfusion at 7 days (or discharge if earlier).

The trial was halted prematurely, after an interim analysis showed no significant difference in the rate of the primary endpoint between the prasugrel and ticagrelor arms—4.0% and 4.1%, respectively (odds ratio=0.98, P=0.939).

Likewise, there was no significant difference between the treatment arms for any of the components of the primary endpoint.

The key secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and stroke within 30 days. There was no significant difference in the rate of this endpoint between the prasugrel and ticagrelor arms—2.7% and 2.5%, respectively (odds ratio=1.06, P=0.864).

“This study did not show any difference between ticagrelor and prasugrel in the early phase of acute myocardial infarction treated by primary PCI,” Dr Widimsky concluded.

He and his colleagues are planning the final follow-up of this study at 1 year, which will be completed in 2017.

Ofatumumab (Arzerra)

Photo courtesy of GSK

The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).

Ofatumumab was previously approved by the FDA for use in combination with chlorambucil to treat previously untreated CLL patients who cannot receive fludarabine-based therapy, as monotherapy for CLL that is refractory to fludarabine and alemtuzumab, and as maintenance therapy for patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.

Ofatumumab is a monoclonal antibody designed to target CD20.

The drug’s prescribing information includes a boxed warning noting that hepatitis B virus reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab. In some cases, this results in fulminant hepatitis, hepatic failure, and death.

The boxed warning also states that progressive multifocal leukoencephalopathy, resulting in death, can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

COMPLEMENT 2 trial

The FDA’s latest approval for ofatumumab is based on results of the phase 3 COMPLEMENT 2 trial. Novartis reported top-line results from this study in April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Ofatumumab (Arzerra)

Photo courtesy of GSK

The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).

Ofatumumab was previously approved by the FDA for use in combination with chlorambucil to treat previously untreated CLL patients who cannot receive fludarabine-based therapy, as monotherapy for CLL that is refractory to fludarabine and alemtuzumab, and as maintenance therapy for patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.

Ofatumumab is a monoclonal antibody designed to target CD20.

The drug’s prescribing information includes a boxed warning noting that hepatitis B virus reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab. In some cases, this results in fulminant hepatitis, hepatic failure, and death.

The boxed warning also states that progressive multifocal leukoencephalopathy, resulting in death, can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

COMPLEMENT 2 trial

The FDA’s latest approval for ofatumumab is based on results of the phase 3 COMPLEMENT 2 trial. Novartis reported top-line results from this study in April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Ofatumumab (Arzerra)

Photo courtesy of GSK

The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).

Ofatumumab was previously approved by the FDA for use in combination with chlorambucil to treat previously untreated CLL patients who cannot receive fludarabine-based therapy, as monotherapy for CLL that is refractory to fludarabine and alemtuzumab, and as maintenance therapy for patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.

Ofatumumab is a monoclonal antibody designed to target CD20.

The drug’s prescribing information includes a boxed warning noting that hepatitis B virus reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab. In some cases, this results in fulminant hepatitis, hepatic failure, and death.

The boxed warning also states that progressive multifocal leukoencephalopathy, resulting in death, can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

COMPLEMENT 2 trial

The FDA’s latest approval for ofatumumab is based on results of the phase 3 COMPLEMENT 2 trial. Novartis reported top-line results from this study in April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Blood in bags and vials

Photo by Daniel Gay

Results of preclinical research may explain why people with blood type O often get more severely ill from cholera than people with other blood types.

The study suggests that, in people with blood type O, cholera toxin hyperactivates a key signaling molecule in intestinal cells.

And high levels of that molecule, cyclic adenosine monophosphate (cAMP), lead to excretion of electrolytes and water—in other words, diarrhea.

“We have shown that blood type influences how strongly cholera toxin activates intestinal cells, leading to diarrhea,” said study author James Fleckenstein, MD, of Washington University School of Medicine in Saint Louis, Missouri.

Dr Fleckenstein and his colleagues reported these findings in The American Journal of Tropical Medicine and Hygiene.

Cholera is caused by Vibrio cholerae, a bacterium that infects cells of the small intestine.

Epidemiologists first noticed 4 decades ago that people with blood type O were more likely to be hospitalized for cholera than people with other blood types, but the reasons for the difference had never been determined.

Although the blood group antigens—A, B, AB, and O—are best known for their presence on red blood cells, they also are found on the surface of many other cell types, including the cells that line the intestine.

To find out what effect cholera toxin has on intestinal cells carrying different blood group antigens, Dr Fleckenstein and his colleagues used clusters of intestinal epithelial stem cells, called enteroids, that can be grown in the lab and differentiated into mature intestinal cells.

The researchers treated 4 groups of enteroids with cholera toxin—2 derived from people with blood type A and 2 from people with blood type O—and measured the amount of cAMP inside the cells. Enteroids from the other 2 blood types—B and AB—were not available at the time the study was done.

The researchers found that levels of cAMP were roughly twice as high in the cells with the type O antigen than in the cells with type A antigen, suggesting that people with type O antigen who were exposed to cholera toxin would suffer more severe diarrhea.

“It is well-established that high levels of this molecule lead to diarrhea, so we’re making the assumption that higher levels lead to even more diarrhea,” said study author F. Matthew Kuhlmann, MD, of Washington University School of Medicine.

“Unfortunately, we have no way directly to link the responses to the volume of diarrhea and, therefore, the severity of disease.”

The researchers confirmed their enteroid results in an intestinal cell line originally derived from a person with blood type A. The cell line was modified to produce the type O antigen instead.

The team found that cholera toxin induced roughly double the amount of cAMP in cells with type O antigen than in those with type A.

Dr Fleckenstein said the researchers are not sure why cholera toxin induces different responses in cells with different blood group antigens on their surfaces.

“The cholera toxin is known to bind weakly to the ABO antigens, so they may be acting as decoys to draw the toxin away from its true target,” Dr Fleckenstein said. “It may be that the type O antigen just isn’t as good of a decoy as the type A antigen.”

Blood in bags and vials

Photo by Daniel Gay

Results of preclinical research may explain why people with blood type O often get more severely ill from cholera than people with other blood types.

The study suggests that, in people with blood type O, cholera toxin hyperactivates a key signaling molecule in intestinal cells.

And high levels of that molecule, cyclic adenosine monophosphate (cAMP), lead to excretion of electrolytes and water—in other words, diarrhea.

“We have shown that blood type influences how strongly cholera toxin activates intestinal cells, leading to diarrhea,” said study author James Fleckenstein, MD, of Washington University School of Medicine in Saint Louis, Missouri.

Dr Fleckenstein and his colleagues reported these findings in The American Journal of Tropical Medicine and Hygiene.

Cholera is caused by Vibrio cholerae, a bacterium that infects cells of the small intestine.

Epidemiologists first noticed 4 decades ago that people with blood type O were more likely to be hospitalized for cholera than people with other blood types, but the reasons for the difference had never been determined.

Although the blood group antigens—A, B, AB, and O—are best known for their presence on red blood cells, they also are found on the surface of many other cell types, including the cells that line the intestine.

To find out what effect cholera toxin has on intestinal cells carrying different blood group antigens, Dr Fleckenstein and his colleagues used clusters of intestinal epithelial stem cells, called enteroids, that can be grown in the lab and differentiated into mature intestinal cells.

The researchers treated 4 groups of enteroids with cholera toxin—2 derived from people with blood type A and 2 from people with blood type O—and measured the amount of cAMP inside the cells. Enteroids from the other 2 blood types—B and AB—were not available at the time the study was done.

The researchers found that levels of cAMP were roughly twice as high in the cells with the type O antigen than in the cells with type A antigen, suggesting that people with type O antigen who were exposed to cholera toxin would suffer more severe diarrhea.

“It is well-established that high levels of this molecule lead to diarrhea, so we’re making the assumption that higher levels lead to even more diarrhea,” said study author F. Matthew Kuhlmann, MD, of Washington University School of Medicine.

“Unfortunately, we have no way directly to link the responses to the volume of diarrhea and, therefore, the severity of disease.”

The researchers confirmed their enteroid results in an intestinal cell line originally derived from a person with blood type A. The cell line was modified to produce the type O antigen instead.

The team found that cholera toxin induced roughly double the amount of cAMP in cells with type O antigen than in those with type A.

Dr Fleckenstein said the researchers are not sure why cholera toxin induces different responses in cells with different blood group antigens on their surfaces.

“The cholera toxin is known to bind weakly to the ABO antigens, so they may be acting as decoys to draw the toxin away from its true target,” Dr Fleckenstein said. “It may be that the type O antigen just isn’t as good of a decoy as the type A antigen.”

Blood in bags and vials

Photo by Daniel Gay

Results of preclinical research may explain why people with blood type O often get more severely ill from cholera than people with other blood types.

The study suggests that, in people with blood type O, cholera toxin hyperactivates a key signaling molecule in intestinal cells.

And high levels of that molecule, cyclic adenosine monophosphate (cAMP), lead to excretion of electrolytes and water—in other words, diarrhea.

“We have shown that blood type influences how strongly cholera toxin activates intestinal cells, leading to diarrhea,” said study author James Fleckenstein, MD, of Washington University School of Medicine in Saint Louis, Missouri.

Dr Fleckenstein and his colleagues reported these findings in The American Journal of Tropical Medicine and Hygiene.

Cholera is caused by Vibrio cholerae, a bacterium that infects cells of the small intestine.

Epidemiologists first noticed 4 decades ago that people with blood type O were more likely to be hospitalized for cholera than people with other blood types, but the reasons for the difference had never been determined.

Although the blood group antigens—A, B, AB, and O—are best known for their presence on red blood cells, they also are found on the surface of many other cell types, including the cells that line the intestine.

To find out what effect cholera toxin has on intestinal cells carrying different blood group antigens, Dr Fleckenstein and his colleagues used clusters of intestinal epithelial stem cells, called enteroids, that can be grown in the lab and differentiated into mature intestinal cells.

The researchers treated 4 groups of enteroids with cholera toxin—2 derived from people with blood type A and 2 from people with blood type O—and measured the amount of cAMP inside the cells. Enteroids from the other 2 blood types—B and AB—were not available at the time the study was done.

The researchers found that levels of cAMP were roughly twice as high in the cells with the type O antigen than in the cells with type A antigen, suggesting that people with type O antigen who were exposed to cholera toxin would suffer more severe diarrhea.

“It is well-established that high levels of this molecule lead to diarrhea, so we’re making the assumption that higher levels lead to even more diarrhea,” said study author F. Matthew Kuhlmann, MD, of Washington University School of Medicine.

“Unfortunately, we have no way directly to link the responses to the volume of diarrhea and, therefore, the severity of disease.”

The researchers confirmed their enteroid results in an intestinal cell line originally derived from a person with blood type A. The cell line was modified to produce the type O antigen instead.

The team found that cholera toxin induced roughly double the amount of cAMP in cells with type O antigen than in those with type A.

Dr Fleckenstein said the researchers are not sure why cholera toxin induces different responses in cells with different blood group antigens on their surfaces.

“The cholera toxin is known to bind weakly to the ABO antigens, so they may be acting as decoys to draw the toxin away from its true target,” Dr Fleckenstein said. “It may be that the type O antigen just isn’t as good of a decoy as the type A antigen.”

Purpose: The purpose of this study is to determine the efficacy of inhibition of mitochondrial antioxidant defense against mesothelioma and whether the cyclin-dependent kinase 4 (CDK4) inhibitor palbociclib sensitizes mesothelioma cells to inhibition of mitochondrial antioxidant defense.

Background: Mesothelioma is a highly fatal cancer with limited therapeutic options. Low expression of the endogenous CDK4 inhibitor p16INK4A has been demonstrated in up to 90% of mesothelioma tumors. CDK4 has also been demonstrated to activate manganese superoxide dismutase, which can decrease superoxide levels in cells and may make them less susceptible to induction of apoptosis. Downregulation of the key mitochondrial antioxidant protein, thioredoxin 2 (Trx2) has been demonstrated to increase reactive oxygen species production in mesothelioma cells resulting in reduced mesothelioma tumor growth. Gentian violet has been demonstrated to result in decreased expression of Trx2, a key mitochondrial antioxidant protein. The goal of this project is to determine whether concomitant targeting of the cell cycle and mitochondrial antioxidant pathways lead to improved efficacy against mesothelioma.

Methods: Mesothelioma cells were treated with compound or control and proliferation was evaluated using Cell Counting Kit 8 (Dojindo). For immunoblotting experiments, detection was performed using enhanced chemiluminescence. Apoptosis was detected via Cell Death Detection ELISAPLUS (Sigma-Aldrich). All experiments were done in duplicate or triplicate.

Data Analysis: IC50 curves were fitted via Origin software.

Results: Previously, we have demonstrated that palbociclib inhibits mesothelioma cell proliferation, inhibits retinoblastoma protein (Rb) phosphorylation, and results in cell cycle arrest. Mesothelioma cells in culture were treated with palbociclib and gentian violet alone and in combination. After 72h incubation with gentian violet, decreased cell proliferation was observed for 3 separate cell lines (IC50 = 365 nM, 870 nM, and 920 nM, respectively). Incubation with gentian violet for 24h resulted in decreased expression of Trx2 in all cell lines and also induced apoptosis in all cell lines. Gentian violetsensitized mesothelioma cells to palbociclib in a cell proliferation assay.

Implications: Gentian violet resulted in a significant decrease in mesothelioma cell proliferation. Palbociclib also sensitizes mesothelioma cells to gentian violet. Further investigation of this combination approach may demonstrate these combinations are useful for mesothelioma treatment.

Purpose: The purpose of this study is to determine the efficacy of inhibition of mitochondrial antioxidant defense against mesothelioma and whether the cyclin-dependent kinase 4 (CDK4) inhibitor palbociclib sensitizes mesothelioma cells to inhibition of mitochondrial antioxidant defense.

Background: Mesothelioma is a highly fatal cancer with limited therapeutic options. Low expression of the endogenous CDK4 inhibitor p16INK4A has been demonstrated in up to 90% of mesothelioma tumors. CDK4 has also been demonstrated to activate manganese superoxide dismutase, which can decrease superoxide levels in cells and may make them less susceptible to induction of apoptosis. Downregulation of the key mitochondrial antioxidant protein, thioredoxin 2 (Trx2) has been demonstrated to increase reactive oxygen species production in mesothelioma cells resulting in reduced mesothelioma tumor growth. Gentian violet has been demonstrated to result in decreased expression of Trx2, a key mitochondrial antioxidant protein. The goal of this project is to determine whether concomitant targeting of the cell cycle and mitochondrial antioxidant pathways lead to improved efficacy against mesothelioma.

Methods: Mesothelioma cells were treated with compound or control and proliferation was evaluated using Cell Counting Kit 8 (Dojindo). For immunoblotting experiments, detection was performed using enhanced chemiluminescence. Apoptosis was detected via Cell Death Detection ELISAPLUS (Sigma-Aldrich). All experiments were done in duplicate or triplicate.

Data Analysis: IC50 curves were fitted via Origin software.

Results: Previously, we have demonstrated that palbociclib inhibits mesothelioma cell proliferation, inhibits retinoblastoma protein (Rb) phosphorylation, and results in cell cycle arrest. Mesothelioma cells in culture were treated with palbociclib and gentian violet alone and in combination. After 72h incubation with gentian violet, decreased cell proliferation was observed for 3 separate cell lines (IC50 = 365 nM, 870 nM, and 920 nM, respectively). Incubation with gentian violet for 24h resulted in decreased expression of Trx2 in all cell lines and also induced apoptosis in all cell lines. Gentian violetsensitized mesothelioma cells to palbociclib in a cell proliferation assay.

Implications: Gentian violet resulted in a significant decrease in mesothelioma cell proliferation. Palbociclib also sensitizes mesothelioma cells to gentian violet. Further investigation of this combination approach may demonstrate these combinations are useful for mesothelioma treatment.

Purpose: The purpose of this study is to determine the efficacy of inhibition of mitochondrial antioxidant defense against mesothelioma and whether the cyclin-dependent kinase 4 (CDK4) inhibitor palbociclib sensitizes mesothelioma cells to inhibition of mitochondrial antioxidant defense.

Background: Mesothelioma is a highly fatal cancer with limited therapeutic options. Low expression of the endogenous CDK4 inhibitor p16INK4A has been demonstrated in up to 90% of mesothelioma tumors. CDK4 has also been demonstrated to activate manganese superoxide dismutase, which can decrease superoxide levels in cells and may make them less susceptible to induction of apoptosis. Downregulation of the key mitochondrial antioxidant protein, thioredoxin 2 (Trx2) has been demonstrated to increase reactive oxygen species production in mesothelioma cells resulting in reduced mesothelioma tumor growth. Gentian violet has been demonstrated to result in decreased expression of Trx2, a key mitochondrial antioxidant protein. The goal of this project is to determine whether concomitant targeting of the cell cycle and mitochondrial antioxidant pathways lead to improved efficacy against mesothelioma.

Methods: Mesothelioma cells were treated with compound or control and proliferation was evaluated using Cell Counting Kit 8 (Dojindo). For immunoblotting experiments, detection was performed using enhanced chemiluminescence. Apoptosis was detected via Cell Death Detection ELISAPLUS (Sigma-Aldrich). All experiments were done in duplicate or triplicate.

Data Analysis: IC50 curves were fitted via Origin software.

Results: Previously, we have demonstrated that palbociclib inhibits mesothelioma cell proliferation, inhibits retinoblastoma protein (Rb) phosphorylation, and results in cell cycle arrest. Mesothelioma cells in culture were treated with palbociclib and gentian violet alone and in combination. After 72h incubation with gentian violet, decreased cell proliferation was observed for 3 separate cell lines (IC50 = 365 nM, 870 nM, and 920 nM, respectively). Incubation with gentian violet for 24h resulted in decreased expression of Trx2 in all cell lines and also induced apoptosis in all cell lines. Gentian violetsensitized mesothelioma cells to palbociclib in a cell proliferation assay.

Implications: Gentian violet resulted in a significant decrease in mesothelioma cell proliferation. Palbociclib also sensitizes mesothelioma cells to gentian violet. Further investigation of this combination approach may demonstrate these combinations are useful for mesothelioma treatment.

Click here to access the September 2016 Digital Edition. 

Table of Contents

• Finally, Some Good News!
• Emerging Cataract Surgery Practice Patterns in the VHA
• Medication List Discrepancies and Therapeutic Duplications Among Dual Use Veterans
• Laboring in the Shadow of the Media: Care and Perceptions of Care in the VA
• Providing Quality Epilepsy Care for Veterans
• Is It All in the Eye of the Beholder? Comparing Pulmonologists’ and Radiologists’ Performance
• Angiomyomatous Hamartoma With Unexplained Hepatosplenomegaly
• Veteran Perceptions, Interest, and Use of Complementary and Alternative Medicine

Click here to access the September 2016 Digital Edition. 

Table of Contents

• Finally, Some Good News!
• Emerging Cataract Surgery Practice Patterns in the VHA
• Medication List Discrepancies and Therapeutic Duplications Among Dual Use Veterans
• Laboring in the Shadow of the Media: Care and Perceptions of Care in the VA
• Providing Quality Epilepsy Care for Veterans
• Is It All in the Eye of the Beholder? Comparing Pulmonologists’ and Radiologists’ Performance
• Angiomyomatous Hamartoma With Unexplained Hepatosplenomegaly
• Veteran Perceptions, Interest, and Use of Complementary and Alternative Medicine

Click here to access the September 2016 Digital Edition. 

Table of Contents

• Finally, Some Good News!
• Emerging Cataract Surgery Practice Patterns in the VHA
• Medication List Discrepancies and Therapeutic Duplications Among Dual Use Veterans
• Laboring in the Shadow of the Media: Care and Perceptions of Care in the VA
• Providing Quality Epilepsy Care for Veterans
• Is It All in the Eye of the Beholder? Comparing Pulmonologists’ and Radiologists’ Performance
• Angiomyomatous Hamartoma With Unexplained Hepatosplenomegaly
• Veteran Perceptions, Interest, and Use of Complementary and Alternative Medicine

Eight weeks of a two-drug combination led to sustained viral response (SVR) in 94% of noncirrhotic, treatment-naive, genotype 1 hepatitis C virus–infected patients, based on a retrospective study of Veterans Affairs health system data presented in the September issue of Gastroenterology.

But VA clinicians prescribed the 8-week regimen to less than half of eligible patients, said George Ioannou, MD, of the Veterans Affairs Puget Sound Health Care System in Seattle. Increasing its use, when appropriate, “could save on costs,” although the currently available interferon-free regimens “leave substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections,” he and his associates wrote.

The two-drug regimen contained sofosbuvir and ledipasvir. Clinical trials of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) have reported SVR rates well above 90%, “with the exception of certain subgroups, such as patients with Child’s B or C cirrhosis and those infected with genotype 3 HCV,” the researchers noted. However, older interferon-based regimens did not perform as well in the real world as in trials, and “it is unclear if this is the case for current interferon-free regimens, or whether the relative ease of administration of these regimens has narrowed the SVR gap between clinical trials and clinical practice.” Questions also persist about how effective the interferon-free regimens are in various HCV genotypes and subgroups, they added (Gastroenterology 2016 Jul 18. doi: 10.1053/j.gastro.2016.05.049). To help answer these questions, they analyzed data from more than 17,000 HCV patients in the VA health care system who received sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir between January 2014 and June 2015. The cohort included about 14,000 patients with genotype 1 infections, about 2,100 patients with genotype 2 infections, about 1,200 patients with genotype 3 infections, and 135 patients with genotype 4 infections. Patients averaged 62 years of age, about half were non-Hispanic white, 29% were non-Hispanic black, and nearly a third had been diagnosed with cirrhosis, including 10% with decompensated cirrhosis.

The VA guidelines recommended 8 weeks instead of 12 weeks of ledipasvir/sofosbuvir for treatment-naive, noncirrhotic, genotype 1 patients with a viral load under 6 million IU/mL, although that recommendation was not FDA approved and was based only on a post hoc analysis of the ION-3 trial, the investigators noted. These concerns seemed to affect practice – of 4,066 eligible patients, only 1,975 (49%) received the 8-week regimen. Notably, however, their rate of SVR 12 weeks after treatment (SVR12) was 95.1% (95% confidence interval, 94% to 96%) – nearly identical to that of patients with the same characteristics who received 12 weeks of treatment (95.8%; 94.7% to 96.8%; P = .6).

Rates of SVR12 did not significantly differ between ledipasvir/sofosbuvir and PrOD regimens, including in multivariable and propensity score–adjusted analyses, the researchers reported. Rates of SVR12 also exceeded 90% in subgroups of treatment-experienced and cirrhotic genotype 1 patients, they added. However, rates of SVR12 were lower for nongenotype 1 infections, as has been observed in trials. Specifically, rates of SVR12 were 90% for genotype 4 patients, 86% for genotype 2 patients who received sofosbuvir and ribavirin, and 75% for genotype 3 patients (including 78% for patients given ledipasvir/sofosbuvir plus ribavirin, 87% for patients given sofosbuvir and pegylated interferon plus ribavirin, and 71% for patients given sofosbuvir monotherapy). For cirrhotic patients, rates of SVR12 were 91% for genotype 1, 77% for genotype 2, 66% for genotype 3, and 84% for genotype 4.

The findings confirm that the new interferon-free regimens “can achieve remarkably high SVR rates in real-world clinical practice, especially in genotype 1–infected patients,” the researchers wrote. The cost of these regimens is “the main obstacle to curing HCV” in as many patients as possible, but is expected to “decline dramatically” as the FDA approves new regimens, they noted. “In fact, costs decreased dramatically within the VA after the completion of our study and after the FDA approved elbasvir/grazoprevir in January 2016.”

The study was funded by the Department of Veterans Affairs. The investigators had no disclosures.

Eight weeks of a two-drug combination led to sustained viral response (SVR) in 94% of noncirrhotic, treatment-naive, genotype 1 hepatitis C virus–infected patients, based on a retrospective study of Veterans Affairs health system data presented in the September issue of Gastroenterology.

But VA clinicians prescribed the 8-week regimen to less than half of eligible patients, said George Ioannou, MD, of the Veterans Affairs Puget Sound Health Care System in Seattle. Increasing its use, when appropriate, “could save on costs,” although the currently available interferon-free regimens “leave substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections,” he and his associates wrote.

The two-drug regimen contained sofosbuvir and ledipasvir. Clinical trials of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) have reported SVR rates well above 90%, “with the exception of certain subgroups, such as patients with Child’s B or C cirrhosis and those infected with genotype 3 HCV,” the researchers noted. However, older interferon-based regimens did not perform as well in the real world as in trials, and “it is unclear if this is the case for current interferon-free regimens, or whether the relative ease of administration of these regimens has narrowed the SVR gap between clinical trials and clinical practice.” Questions also persist about how effective the interferon-free regimens are in various HCV genotypes and subgroups, they added (Gastroenterology 2016 Jul 18. doi: 10.1053/j.gastro.2016.05.049). To help answer these questions, they analyzed data from more than 17,000 HCV patients in the VA health care system who received sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir between January 2014 and June 2015. The cohort included about 14,000 patients with genotype 1 infections, about 2,100 patients with genotype 2 infections, about 1,200 patients with genotype 3 infections, and 135 patients with genotype 4 infections. Patients averaged 62 years of age, about half were non-Hispanic white, 29% were non-Hispanic black, and nearly a third had been diagnosed with cirrhosis, including 10% with decompensated cirrhosis.

The VA guidelines recommended 8 weeks instead of 12 weeks of ledipasvir/sofosbuvir for treatment-naive, noncirrhotic, genotype 1 patients with a viral load under 6 million IU/mL, although that recommendation was not FDA approved and was based only on a post hoc analysis of the ION-3 trial, the investigators noted. These concerns seemed to affect practice – of 4,066 eligible patients, only 1,975 (49%) received the 8-week regimen. Notably, however, their rate of SVR 12 weeks after treatment (SVR12) was 95.1% (95% confidence interval, 94% to 96%) – nearly identical to that of patients with the same characteristics who received 12 weeks of treatment (95.8%; 94.7% to 96.8%; P = .6).

Rates of SVR12 did not significantly differ between ledipasvir/sofosbuvir and PrOD regimens, including in multivariable and propensity score–adjusted analyses, the researchers reported. Rates of SVR12 also exceeded 90% in subgroups of treatment-experienced and cirrhotic genotype 1 patients, they added. However, rates of SVR12 were lower for nongenotype 1 infections, as has been observed in trials. Specifically, rates of SVR12 were 90% for genotype 4 patients, 86% for genotype 2 patients who received sofosbuvir and ribavirin, and 75% for genotype 3 patients (including 78% for patients given ledipasvir/sofosbuvir plus ribavirin, 87% for patients given sofosbuvir and pegylated interferon plus ribavirin, and 71% for patients given sofosbuvir monotherapy). For cirrhotic patients, rates of SVR12 were 91% for genotype 1, 77% for genotype 2, 66% for genotype 3, and 84% for genotype 4.

The findings confirm that the new interferon-free regimens “can achieve remarkably high SVR rates in real-world clinical practice, especially in genotype 1–infected patients,” the researchers wrote. The cost of these regimens is “the main obstacle to curing HCV” in as many patients as possible, but is expected to “decline dramatically” as the FDA approves new regimens, they noted. “In fact, costs decreased dramatically within the VA after the completion of our study and after the FDA approved elbasvir/grazoprevir in January 2016.”

The study was funded by the Department of Veterans Affairs. The investigators had no disclosures.

Eight weeks of a two-drug combination led to sustained viral response (SVR) in 94% of noncirrhotic, treatment-naive, genotype 1 hepatitis C virus–infected patients, based on a retrospective study of Veterans Affairs health system data presented in the September issue of Gastroenterology.

But VA clinicians prescribed the 8-week regimen to less than half of eligible patients, said George Ioannou, MD, of the Veterans Affairs Puget Sound Health Care System in Seattle. Increasing its use, when appropriate, “could save on costs,” although the currently available interferon-free regimens “leave substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections,” he and his associates wrote.

The two-drug regimen contained sofosbuvir and ledipasvir. Clinical trials of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) have reported SVR rates well above 90%, “with the exception of certain subgroups, such as patients with Child’s B or C cirrhosis and those infected with genotype 3 HCV,” the researchers noted. However, older interferon-based regimens did not perform as well in the real world as in trials, and “it is unclear if this is the case for current interferon-free regimens, or whether the relative ease of administration of these regimens has narrowed the SVR gap between clinical trials and clinical practice.” Questions also persist about how effective the interferon-free regimens are in various HCV genotypes and subgroups, they added (Gastroenterology 2016 Jul 18. doi: 10.1053/j.gastro.2016.05.049). To help answer these questions, they analyzed data from more than 17,000 HCV patients in the VA health care system who received sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir between January 2014 and June 2015. The cohort included about 14,000 patients with genotype 1 infections, about 2,100 patients with genotype 2 infections, about 1,200 patients with genotype 3 infections, and 135 patients with genotype 4 infections. Patients averaged 62 years of age, about half were non-Hispanic white, 29% were non-Hispanic black, and nearly a third had been diagnosed with cirrhosis, including 10% with decompensated cirrhosis.

The VA guidelines recommended 8 weeks instead of 12 weeks of ledipasvir/sofosbuvir for treatment-naive, noncirrhotic, genotype 1 patients with a viral load under 6 million IU/mL, although that recommendation was not FDA approved and was based only on a post hoc analysis of the ION-3 trial, the investigators noted. These concerns seemed to affect practice – of 4,066 eligible patients, only 1,975 (49%) received the 8-week regimen. Notably, however, their rate of SVR 12 weeks after treatment (SVR12) was 95.1% (95% confidence interval, 94% to 96%) – nearly identical to that of patients with the same characteristics who received 12 weeks of treatment (95.8%; 94.7% to 96.8%; P = .6).

Rates of SVR12 did not significantly differ between ledipasvir/sofosbuvir and PrOD regimens, including in multivariable and propensity score–adjusted analyses, the researchers reported. Rates of SVR12 also exceeded 90% in subgroups of treatment-experienced and cirrhotic genotype 1 patients, they added. However, rates of SVR12 were lower for nongenotype 1 infections, as has been observed in trials. Specifically, rates of SVR12 were 90% for genotype 4 patients, 86% for genotype 2 patients who received sofosbuvir and ribavirin, and 75% for genotype 3 patients (including 78% for patients given ledipasvir/sofosbuvir plus ribavirin, 87% for patients given sofosbuvir and pegylated interferon plus ribavirin, and 71% for patients given sofosbuvir monotherapy). For cirrhotic patients, rates of SVR12 were 91% for genotype 1, 77% for genotype 2, 66% for genotype 3, and 84% for genotype 4.

The findings confirm that the new interferon-free regimens “can achieve remarkably high SVR rates in real-world clinical practice, especially in genotype 1–infected patients,” the researchers wrote. The cost of these regimens is “the main obstacle to curing HCV” in as many patients as possible, but is expected to “decline dramatically” as the FDA approves new regimens, they noted. “In fact, costs decreased dramatically within the VA after the completion of our study and after the FDA approved elbasvir/grazoprevir in January 2016.”

The study was funded by the Department of Veterans Affairs. The investigators had no disclosures.

Fecal immunochemical testing and colonoscopy detected colorectal cancer (CRC) more effectively and cheaply than did multitarget stool DNA testing, based on a Markov model that assumed equal rates of participation in the three strategies, according to a report in the September issue of Gastroenterology.

Multitarget stool DNA testing (MT-sDNA) “may be a cost-effective alternative if it can achieve patient participation rates that are high enough compared with those of FIT [fecal immunochemical testing] that paying for its higher test cost can be justified,” wrote Uri Ladabaum, MD, and Ajitha Mannalithara, PhD, of Stanford (Calif.) University.

Studies have yielded mixed results about whether FIT or fecal DNA testing are preferable for CRC detection. In one recent large prospective study of patients at average CRC risk, a MT-sDNA test that included KRAS mutations, aberrant NDRG4 and BMP3 methylation, and hemoglobin outperformed FIT for detecting CRC and precancerous lesions but also yielded more false positives, the researchers noted.

Although many decision analyses have examined the efficacy and cost of CRC screening strategies, they have not delved into “the complex patterns of screening participation over time that are now being described (consistent screeners, late entrants, dropouts, intermittent screeners, consistent non-responders),” accounted for variable participation in organized and opportunistic screening programs, or controlled for differential reimbursement rates for public versus private insurance, they added (Gastroenterology 2016 Jun 7. doi: 10.1053/j.gastro.2016.06.003).

Dr. Ladabaum and Dr. Mannalithara therefore constructed a Markov model of patients at average risk for CRC to compare the efficacy and costs of MT-sDNA, colonoscopy, and FIT. The model included numerous variables, such as disease states ranging from a small adenomatous polyp to disseminated CRC, longitudinal changes in rates of participation for both opportunistic screening and organized screening programs, and different rates of commercial and Medicare reimbursement.

Assuming optimal adherence, an annual FIT test and colonoscopy every 10 years were more effective and less costly than MT-sDNA every 3 years, the researchers found. Compared with successful FIT screening programs – which have a 50% rate of consistent participation and a 27% rate of intermittent participation and cost about $153 per patient per testing cycle – an MT-sDNA program would need to have at least a 68% rate of consistent participation and a 32% rate of intermittent (every 3 years) participation, or would need to cost 60% less than it does now ($260 for commercial payment and $197 for Medicare payment in 2015) to be preferable when assuming a threshold of $100,000 for every extra quality-adjusted life year (QALY) gained. MT-sDNA every 3 years, however, would be more cost-effective than opportunistic FIT screening if participation rates were more than 1.7 times those that are typical of opportunistic FIT (15% consistent participation and 30% intermittent participation).

These results held up in various subgroup analyses, and FIT was preferred in 99% of iterations in a Monte Carlo simulation that assumed equal participation rates and the same $100,000 per QALY threshold. “For the MT-sDNA test to be cost-effective, the patient support program included in its cost would need to achieve substantially higher participation rates than those of FIT, whether in organized programs or under the opportunistic screening setting more common in the U.S. than in the rest of the world,” they concluded.

The study was funded by an unrestricted research grant from Exact Science Corp. Dr. Ladabaum reported consulting for ESC in 2014 and disclosed current consulting or advisory relationships with Given Imaging and Mauna Kea Technologies. Dr. Mannalithara had no disclosures.

Fecal immunochemical testing and colonoscopy detected colorectal cancer (CRC) more effectively and cheaply than did multitarget stool DNA testing, based on a Markov model that assumed equal rates of participation in the three strategies, according to a report in the September issue of Gastroenterology.

Multitarget stool DNA testing (MT-sDNA) “may be a cost-effective alternative if it can achieve patient participation rates that are high enough compared with those of FIT [fecal immunochemical testing] that paying for its higher test cost can be justified,” wrote Uri Ladabaum, MD, and Ajitha Mannalithara, PhD, of Stanford (Calif.) University.

Studies have yielded mixed results about whether FIT or fecal DNA testing are preferable for CRC detection. In one recent large prospective study of patients at average CRC risk, a MT-sDNA test that included KRAS mutations, aberrant NDRG4 and BMP3 methylation, and hemoglobin outperformed FIT for detecting CRC and precancerous lesions but also yielded more false positives, the researchers noted.

Although many decision analyses have examined the efficacy and cost of CRC screening strategies, they have not delved into “the complex patterns of screening participation over time that are now being described (consistent screeners, late entrants, dropouts, intermittent screeners, consistent non-responders),” accounted for variable participation in organized and opportunistic screening programs, or controlled for differential reimbursement rates for public versus private insurance, they added (Gastroenterology 2016 Jun 7. doi: 10.1053/j.gastro.2016.06.003).

Dr. Ladabaum and Dr. Mannalithara therefore constructed a Markov model of patients at average risk for CRC to compare the efficacy and costs of MT-sDNA, colonoscopy, and FIT. The model included numerous variables, such as disease states ranging from a small adenomatous polyp to disseminated CRC, longitudinal changes in rates of participation for both opportunistic screening and organized screening programs, and different rates of commercial and Medicare reimbursement.

Assuming optimal adherence, an annual FIT test and colonoscopy every 10 years were more effective and less costly than MT-sDNA every 3 years, the researchers found. Compared with successful FIT screening programs – which have a 50% rate of consistent participation and a 27% rate of intermittent participation and cost about $153 per patient per testing cycle – an MT-sDNA program would need to have at least a 68% rate of consistent participation and a 32% rate of intermittent (every 3 years) participation, or would need to cost 60% less than it does now ($260 for commercial payment and $197 for Medicare payment in 2015) to be preferable when assuming a threshold of $100,000 for every extra quality-adjusted life year (QALY) gained. MT-sDNA every 3 years, however, would be more cost-effective than opportunistic FIT screening if participation rates were more than 1.7 times those that are typical of opportunistic FIT (15% consistent participation and 30% intermittent participation).

These results held up in various subgroup analyses, and FIT was preferred in 99% of iterations in a Monte Carlo simulation that assumed equal participation rates and the same $100,000 per QALY threshold. “For the MT-sDNA test to be cost-effective, the patient support program included in its cost would need to achieve substantially higher participation rates than those of FIT, whether in organized programs or under the opportunistic screening setting more common in the U.S. than in the rest of the world,” they concluded.

The study was funded by an unrestricted research grant from Exact Science Corp. Dr. Ladabaum reported consulting for ESC in 2014 and disclosed current consulting or advisory relationships with Given Imaging and Mauna Kea Technologies. Dr. Mannalithara had no disclosures.

Fecal immunochemical testing and colonoscopy detected colorectal cancer (CRC) more effectively and cheaply than did multitarget stool DNA testing, based on a Markov model that assumed equal rates of participation in the three strategies, according to a report in the September issue of Gastroenterology.

Multitarget stool DNA testing (MT-sDNA) “may be a cost-effective alternative if it can achieve patient participation rates that are high enough compared with those of FIT [fecal immunochemical testing] that paying for its higher test cost can be justified,” wrote Uri Ladabaum, MD, and Ajitha Mannalithara, PhD, of Stanford (Calif.) University.

Studies have yielded mixed results about whether FIT or fecal DNA testing are preferable for CRC detection. In one recent large prospective study of patients at average CRC risk, a MT-sDNA test that included KRAS mutations, aberrant NDRG4 and BMP3 methylation, and hemoglobin outperformed FIT for detecting CRC and precancerous lesions but also yielded more false positives, the researchers noted.

Although many decision analyses have examined the efficacy and cost of CRC screening strategies, they have not delved into “the complex patterns of screening participation over time that are now being described (consistent screeners, late entrants, dropouts, intermittent screeners, consistent non-responders),” accounted for variable participation in organized and opportunistic screening programs, or controlled for differential reimbursement rates for public versus private insurance, they added (Gastroenterology 2016 Jun 7. doi: 10.1053/j.gastro.2016.06.003).

Dr. Ladabaum and Dr. Mannalithara therefore constructed a Markov model of patients at average risk for CRC to compare the efficacy and costs of MT-sDNA, colonoscopy, and FIT. The model included numerous variables, such as disease states ranging from a small adenomatous polyp to disseminated CRC, longitudinal changes in rates of participation for both opportunistic screening and organized screening programs, and different rates of commercial and Medicare reimbursement.

Assuming optimal adherence, an annual FIT test and colonoscopy every 10 years were more effective and less costly than MT-sDNA every 3 years, the researchers found. Compared with successful FIT screening programs – which have a 50% rate of consistent participation and a 27% rate of intermittent participation and cost about $153 per patient per testing cycle – an MT-sDNA program would need to have at least a 68% rate of consistent participation and a 32% rate of intermittent (every 3 years) participation, or would need to cost 60% less than it does now ($260 for commercial payment and $197 for Medicare payment in 2015) to be preferable when assuming a threshold of $100,000 for every extra quality-adjusted life year (QALY) gained. MT-sDNA every 3 years, however, would be more cost-effective than opportunistic FIT screening if participation rates were more than 1.7 times those that are typical of opportunistic FIT (15% consistent participation and 30% intermittent participation).

These results held up in various subgroup analyses, and FIT was preferred in 99% of iterations in a Monte Carlo simulation that assumed equal participation rates and the same $100,000 per QALY threshold. “For the MT-sDNA test to be cost-effective, the patient support program included in its cost would need to achieve substantially higher participation rates than those of FIT, whether in organized programs or under the opportunistic screening setting more common in the U.S. than in the rest of the world,” they concluded.

The study was funded by an unrestricted research grant from Exact Science Corp. Dr. Ladabaum reported consulting for ESC in 2014 and disclosed current consulting or advisory relationships with Given Imaging and Mauna Kea Technologies. Dr. Mannalithara had no disclosures.

Targeted and regular outpatient care before conception helped prevent relapse of inflammatory bowel disease (IBD) during pregnancy, according to a single-center prospective observational study reported in the September issue of Clinical Gastroenterology and Hepatology.

Women who received such care had about 50% lower odds of relapse while pregnant compared with women seen only after conception, said Alison de Lima, MD, PhD, of Erasmus MC–University Medical Hospital Rotterdam (the Netherlands) and her associates. “Preconception care seems effective in achieving desirable behavioral modifications in IBD women in terms of folic acid intake, smoking cessation, and correct IBD medication adherence, eventually reducing disease relapse during pregnancy. Most importantly, preconception care positively influences birth outcomes,” the investigators concluded.

©varaphoto/Thinkstock

Several recent studies have reported “incorrect beliefs, unfounded fears, and insufficient knowledge” among women with IBD when it comes to pregnancy, the researchers noted. These beliefs can undermine medication adherence, potentially increasing the risk of complications and poor birth outcomes, they added. Studies have confirmed the value of preconception care for chronic diseases such as diabetes, but none had done so for IBD (Clin Gastroenterol Hepatol. 2016 Mar 18. doi: 10.1016/j.cgh.2016.03.018). Therefore, Dr. de Lima and her associates prospectively followed 317 women seen at the IBD preconception outpatient clinic at a tertiary referral hospital during 2008-2014. A total of 155 patients first visited the clinic before becoming pregnant, while the other 162 patients did so only after conception. New patient visits lasted about 30-45 minutes and included fecal calprotectin testing to assess disease activity, education about the need to avoid conceiving during a disease flare, and general advice about taking folic acid, quitting smoking, and avoiding alcohol during pregnancy. Follow-up visits, which occurred every 3 months before pregnancy and every 2 months thereafter, included clinical assessments of disease activity, maternal serum testing to assess compliance with antitumor necrosis factor and thiopurine therapy, and assessments of folic acid supplementation, smoking, and alcohol use.

Patients who received such care before conceiving tended to be younger (29.7 vs. 31.4 years; P = .001), were more often nulliparous (76% vs. 51%; P = .0001), and had a shorter history of IBD (5.1 vs. 8 years; P = .0001), compared with the postconception care group, the researchers said. However, after researchers controlled for parity, disease duration, and the number of relapses in the year before pregnancy, the preconception care group had a nearly sixfold greater odds of adhering to IBD medications during pregnancy (adjusted odds ratio, 5.7; 95% confidence interval, 1.9-17.3), about a fivefold greater odds of sufficient folic acid intake (aOR, 5.3; 95% CI, 2.7-10.3), and a more than fourfold odds of smoking cessation during pregnancy (aOR, 4.63; 95% CI, 1.2-17.6). Notably, preconception care was tied to a 49% lower odds of disease relapse during pregnancy (aOR, 0.51; 95% CI; 0.28-0.95) and to a nearly 50% lower rate of low birth weight (birth weight less than 2,500 g).

“To our surprise, this study did not detect an effect of preconception care on periconceptional disease activity,” the researchers said – even though they strove to educate patients on this concept. “We can only speculate about the explanation for this finding, but we believe this could be a result of a discrepancy between physician-declared disease remission and the patient’s own feeling of well-being combined with a strong reproductive desire.”

The investigators reported no funding sources, and Dr. de Lima had no disclosures. Two coinvestigators reported ties to Merck Sharp & Dohme, Abbott, Shire, and Ferring.

Targeted and regular outpatient care before conception helped prevent relapse of inflammatory bowel disease (IBD) during pregnancy, according to a single-center prospective observational study reported in the September issue of Clinical Gastroenterology and Hepatology.

Women who received such care had about 50% lower odds of relapse while pregnant compared with women seen only after conception, said Alison de Lima, MD, PhD, of Erasmus MC–University Medical Hospital Rotterdam (the Netherlands) and her associates. “Preconception care seems effective in achieving desirable behavioral modifications in IBD women in terms of folic acid intake, smoking cessation, and correct IBD medication adherence, eventually reducing disease relapse during pregnancy. Most importantly, preconception care positively influences birth outcomes,” the investigators concluded.

©varaphoto/Thinkstock

Several recent studies have reported “incorrect beliefs, unfounded fears, and insufficient knowledge” among women with IBD when it comes to pregnancy, the researchers noted. These beliefs can undermine medication adherence, potentially increasing the risk of complications and poor birth outcomes, they added. Studies have confirmed the value of preconception care for chronic diseases such as diabetes, but none had done so for IBD (Clin Gastroenterol Hepatol. 2016 Mar 18. doi: 10.1016/j.cgh.2016.03.018). Therefore, Dr. de Lima and her associates prospectively followed 317 women seen at the IBD preconception outpatient clinic at a tertiary referral hospital during 2008-2014. A total of 155 patients first visited the clinic before becoming pregnant, while the other 162 patients did so only after conception. New patient visits lasted about 30-45 minutes and included fecal calprotectin testing to assess disease activity, education about the need to avoid conceiving during a disease flare, and general advice about taking folic acid, quitting smoking, and avoiding alcohol during pregnancy. Follow-up visits, which occurred every 3 months before pregnancy and every 2 months thereafter, included clinical assessments of disease activity, maternal serum testing to assess compliance with antitumor necrosis factor and thiopurine therapy, and assessments of folic acid supplementation, smoking, and alcohol use.

Patients who received such care before conceiving tended to be younger (29.7 vs. 31.4 years; P = .001), were more often nulliparous (76% vs. 51%; P = .0001), and had a shorter history of IBD (5.1 vs. 8 years; P = .0001), compared with the postconception care group, the researchers said. However, after researchers controlled for parity, disease duration, and the number of relapses in the year before pregnancy, the preconception care group had a nearly sixfold greater odds of adhering to IBD medications during pregnancy (adjusted odds ratio, 5.7; 95% confidence interval, 1.9-17.3), about a fivefold greater odds of sufficient folic acid intake (aOR, 5.3; 95% CI, 2.7-10.3), and a more than fourfold odds of smoking cessation during pregnancy (aOR, 4.63; 95% CI, 1.2-17.6). Notably, preconception care was tied to a 49% lower odds of disease relapse during pregnancy (aOR, 0.51; 95% CI; 0.28-0.95) and to a nearly 50% lower rate of low birth weight (birth weight less than 2,500 g).

“To our surprise, this study did not detect an effect of preconception care on periconceptional disease activity,” the researchers said – even though they strove to educate patients on this concept. “We can only speculate about the explanation for this finding, but we believe this could be a result of a discrepancy between physician-declared disease remission and the patient’s own feeling of well-being combined with a strong reproductive desire.”

The investigators reported no funding sources, and Dr. de Lima had no disclosures. Two coinvestigators reported ties to Merck Sharp & Dohme, Abbott, Shire, and Ferring.

Targeted and regular outpatient care before conception helped prevent relapse of inflammatory bowel disease (IBD) during pregnancy, according to a single-center prospective observational study reported in the September issue of Clinical Gastroenterology and Hepatology.

Women who received such care had about 50% lower odds of relapse while pregnant compared with women seen only after conception, said Alison de Lima, MD, PhD, of Erasmus MC–University Medical Hospital Rotterdam (the Netherlands) and her associates. “Preconception care seems effective in achieving desirable behavioral modifications in IBD women in terms of folic acid intake, smoking cessation, and correct IBD medication adherence, eventually reducing disease relapse during pregnancy. Most importantly, preconception care positively influences birth outcomes,” the investigators concluded.

©varaphoto/Thinkstock

Several recent studies have reported “incorrect beliefs, unfounded fears, and insufficient knowledge” among women with IBD when it comes to pregnancy, the researchers noted. These beliefs can undermine medication adherence, potentially increasing the risk of complications and poor birth outcomes, they added. Studies have confirmed the value of preconception care for chronic diseases such as diabetes, but none had done so for IBD (Clin Gastroenterol Hepatol. 2016 Mar 18. doi: 10.1016/j.cgh.2016.03.018). Therefore, Dr. de Lima and her associates prospectively followed 317 women seen at the IBD preconception outpatient clinic at a tertiary referral hospital during 2008-2014. A total of 155 patients first visited the clinic before becoming pregnant, while the other 162 patients did so only after conception. New patient visits lasted about 30-45 minutes and included fecal calprotectin testing to assess disease activity, education about the need to avoid conceiving during a disease flare, and general advice about taking folic acid, quitting smoking, and avoiding alcohol during pregnancy. Follow-up visits, which occurred every 3 months before pregnancy and every 2 months thereafter, included clinical assessments of disease activity, maternal serum testing to assess compliance with antitumor necrosis factor and thiopurine therapy, and assessments of folic acid supplementation, smoking, and alcohol use.

Patients who received such care before conceiving tended to be younger (29.7 vs. 31.4 years; P = .001), were more often nulliparous (76% vs. 51%; P = .0001), and had a shorter history of IBD (5.1 vs. 8 years; P = .0001), compared with the postconception care group, the researchers said. However, after researchers controlled for parity, disease duration, and the number of relapses in the year before pregnancy, the preconception care group had a nearly sixfold greater odds of adhering to IBD medications during pregnancy (adjusted odds ratio, 5.7; 95% confidence interval, 1.9-17.3), about a fivefold greater odds of sufficient folic acid intake (aOR, 5.3; 95% CI, 2.7-10.3), and a more than fourfold odds of smoking cessation during pregnancy (aOR, 4.63; 95% CI, 1.2-17.6). Notably, preconception care was tied to a 49% lower odds of disease relapse during pregnancy (aOR, 0.51; 95% CI; 0.28-0.95) and to a nearly 50% lower rate of low birth weight (birth weight less than 2,500 g).

“To our surprise, this study did not detect an effect of preconception care on periconceptional disease activity,” the researchers said – even though they strove to educate patients on this concept. “We can only speculate about the explanation for this finding, but we believe this could be a result of a discrepancy between physician-declared disease remission and the patient’s own feeling of well-being combined with a strong reproductive desire.”

The investigators reported no funding sources, and Dr. de Lima had no disclosures. Two coinvestigators reported ties to Merck Sharp & Dohme, Abbott, Shire, and Ferring.