SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel supported approval of cangrelor, a short-acting, intravenous antiplatelet drug, for use in patients undergoing percutaneous coronary intervention, with precautions that it not be used widely or indiscriminately.

At a meeting on April 15, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-2, with one abstention, that cangrelor should be approved as an adjunct to PCI “for reducing the periprocedural thrombotic events, such as MI, stent thrombosis, and ischemia-driven revascularization.” The proposed indication includes the statement that use is for patients undergoing PCI “who have not received an oral P2Y₁₂ inhibitor prior to the PCI procedure and in whom oral therapy with P2Y₁₂ inhibitors is not feasible or desirable.”

Cangrelor, a P2Y₁₂ receptor inhibitor, has a half-life of 3-6 minutes, and platelet function completely returns to normal within 1 hour of stopping the infusion, according to the product’s sponsor, the Medicines Company.

The vote was based on analyses of revised endpoints of the data from the CHAMPION PHOENIX study, which compared cangrelor to clopidogrel in more than 11,000 patients undergoing PCI. The same panel voted 7-2 against approval in February 2014, for reasons that included doubts about the clinical consequences of some of the endpoints of the trial.

At the request of the FDA, the company reanalyzed the data, dropping intraprocedural stent thrombosis and MIs that did not meet the SCAI (Society for Cardiovascular Angiography Interventions) criteria for a clinically relevant MI from the primary endpoint. At 48 hours, 1.4% of those in the cangrelor arm met this revised endpoint, vs. 2.1% of those in the clopidogrel arm, for an odds ratio of 0.69 (P = .011). Most of the panel agreed that these analyses showed the drug had a beneficial effect.

Deaths and serious adverse events were similar between cangrelor and clopidogrel, but bleeding events were more common among patients treated with cangrelor, according to the company. A risk-benefit analysis, which took into account bleeding events, provided by the FDA concluded that the “benefit of cangrelor is small, but the risk is smaller.”

“There’s a great responsibility that this gets used appropriately and [is] not overused,” said Dr. James de Lemos, who voted against approval at the last meeting but voted for approval at this meeting. Dr. de Lemos, distinguished chair in cardiology and professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said that his concerns about the robustness of the primary endpoint that had been “mostly addressed” by the FDA’s and company’s analyses.

However, he added that he remained concerned by the very narrow clinical benefit of the drug "relative to the risks and relative to what I worry will be the potential use of the drug.”

”What I would hope is that this drug is used very selectively and very narrowly in circumstances where P2Y₁₂ inhibitors cannot be used appropriately,” he commented. “If it is used broadly and indiscriminately, it will not only be expensive but it [also] will expose low-risk patients to unnecessary bleeding, some of which can be quite substantial.”

The FDA usually follows the recommendations of its advisory panels. The members of the panel had no relevant disclosures.

[email protected]

“It’s best to let her cry it out.” Easy advice to give, but not always easy to follow. The simplest recommendations from pediatricians can pose great challenges, at least initially, for parents. As trainees in pediatrics, we learn the script, but we do not always understand the reality of implementing our advice. Before becoming a parent, “crying it out” seemed the obvious and easy choice. Now, as a parent, I have felt the desperate necessity of getting a child to fall asleep. Although I would never condone unsafe sleeping practices, I understand what drives parents to such extremes.

When the dreaded 2-month-visit came around, I also felt the angst of intentionally putting your child through pain. Sweat dripped down my forehead and my vision blurred when I first saw the nurse immunize my son. Before this, I had ordered countless vaccinations for other patients, and I heard their screaming every day in the halls of clinic as background noise. Yet, seeing my own son being held down and jabbed with a needle was hard to bear. His high-pitched scream seemed perfectly calibrated to pound me with guilt. Of course, I knew the science and I had no fear of adverse events, but seeing your own child in pain does strange things to you. It strikes the same evolutionary chord that sends parents running into traffic to save their babies.

As trainees, many of us have put off having children until later in life. There is nothing wrong with this choice; however, it means that many of us lack the firsthand experience of parenting. We may not know that something as simple as getting a toddler to sit at the dinner table to eat anything can be a night-long struggle. To better prepare new parents and to better understand seasoned parents, we ought to solicit their experiences during office visits. By simply listening for 2 minutes, we can give parents a chance to vent (often well needed and deserved), and we can store their experiences in our memory for future use. Just as we stow away the image of the lacy rash of Fifth disease, we also should stockpile parenting tidbits. The only way to empathize with people going through something foreign to us is to acquire surrogate experiences. Parents in our clinics carry expansive libraries of these experiences, and we should not waste this opportunity.

By better understanding the realities of parenting, we can learn to frame our recommendations in terms that resonate with parents. We can preface our advice with challenges the parents can expect. We can remind them that parenting is hard, but their struggles are normal. When we better understand parents, they can better understand us.

Dr. Sisk is a pediatrics resident at St. Louis Children’s Hospital. E-mail him at [email protected].

“It’s best to let her cry it out.” Easy advice to give, but not always easy to follow. The simplest recommendations from pediatricians can pose great challenges, at least initially, for parents. As trainees in pediatrics, we learn the script, but we do not always understand the reality of implementing our advice. Before becoming a parent, “crying it out” seemed the obvious and easy choice. Now, as a parent, I have felt the desperate necessity of getting a child to fall asleep. Although I would never condone unsafe sleeping practices, I understand what drives parents to such extremes.

When the dreaded 2-month-visit came around, I also felt the angst of intentionally putting your child through pain. Sweat dripped down my forehead and my vision blurred when I first saw the nurse immunize my son. Before this, I had ordered countless vaccinations for other patients, and I heard their screaming every day in the halls of clinic as background noise. Yet, seeing my own son being held down and jabbed with a needle was hard to bear. His high-pitched scream seemed perfectly calibrated to pound me with guilt. Of course, I knew the science and I had no fear of adverse events, but seeing your own child in pain does strange things to you. It strikes the same evolutionary chord that sends parents running into traffic to save their babies.

As trainees, many of us have put off having children until later in life. There is nothing wrong with this choice; however, it means that many of us lack the firsthand experience of parenting. We may not know that something as simple as getting a toddler to sit at the dinner table to eat anything can be a night-long struggle. To better prepare new parents and to better understand seasoned parents, we ought to solicit their experiences during office visits. By simply listening for 2 minutes, we can give parents a chance to vent (often well needed and deserved), and we can store their experiences in our memory for future use. Just as we stow away the image of the lacy rash of Fifth disease, we also should stockpile parenting tidbits. The only way to empathize with people going through something foreign to us is to acquire surrogate experiences. Parents in our clinics carry expansive libraries of these experiences, and we should not waste this opportunity.

By better understanding the realities of parenting, we can learn to frame our recommendations in terms that resonate with parents. We can preface our advice with challenges the parents can expect. We can remind them that parenting is hard, but their struggles are normal. When we better understand parents, they can better understand us.

Dr. Sisk is a pediatrics resident at St. Louis Children’s Hospital. E-mail him at [email protected].

“It’s best to let her cry it out.” Easy advice to give, but not always easy to follow. The simplest recommendations from pediatricians can pose great challenges, at least initially, for parents. As trainees in pediatrics, we learn the script, but we do not always understand the reality of implementing our advice. Before becoming a parent, “crying it out” seemed the obvious and easy choice. Now, as a parent, I have felt the desperate necessity of getting a child to fall asleep. Although I would never condone unsafe sleeping practices, I understand what drives parents to such extremes.

When the dreaded 2-month-visit came around, I also felt the angst of intentionally putting your child through pain. Sweat dripped down my forehead and my vision blurred when I first saw the nurse immunize my son. Before this, I had ordered countless vaccinations for other patients, and I heard their screaming every day in the halls of clinic as background noise. Yet, seeing my own son being held down and jabbed with a needle was hard to bear. His high-pitched scream seemed perfectly calibrated to pound me with guilt. Of course, I knew the science and I had no fear of adverse events, but seeing your own child in pain does strange things to you. It strikes the same evolutionary chord that sends parents running into traffic to save their babies.

As trainees, many of us have put off having children until later in life. There is nothing wrong with this choice; however, it means that many of us lack the firsthand experience of parenting. We may not know that something as simple as getting a toddler to sit at the dinner table to eat anything can be a night-long struggle. To better prepare new parents and to better understand seasoned parents, we ought to solicit their experiences during office visits. By simply listening for 2 minutes, we can give parents a chance to vent (often well needed and deserved), and we can store their experiences in our memory for future use. Just as we stow away the image of the lacy rash of Fifth disease, we also should stockpile parenting tidbits. The only way to empathize with people going through something foreign to us is to acquire surrogate experiences. Parents in our clinics carry expansive libraries of these experiences, and we should not waste this opportunity.

By better understanding the realities of parenting, we can learn to frame our recommendations in terms that resonate with parents. We can preface our advice with challenges the parents can expect. We can remind them that parenting is hard, but their struggles are normal. When we better understand parents, they can better understand us.

Dr. Sisk is a pediatrics resident at St. Louis Children’s Hospital. E-mail him at [email protected].

SNOWMASS, COLO.– The sun may be setting on the use of aspirin for thromboprophylaxis in patients with nonvalvular atrial fibrillation. The 2014 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines are unique among the major international guidelines in giving a modest IIb, Level of Evidence C endorsement to the option of aspirin or no treatment in patients with atrial fibrillation (AF) and a CHA₂DS₂-VASc score of 1. In contrast, the 2014 U.K. NICE (National Institute for Health and Care Excellence) guidelines, the 2013 Asian Pacific Heart Rhythm Society guidelines, and the 2012 European Society of Cardiology guidelines all recommend consideration of oral anticoagulation – eschewing aspirin – in patients with a CHA₂DS₂-VASc score of 1 or more, Dr. Bernard J. Gersh noted at the Annual Cardiovascular Conference at Snowmass.

The NICE guidelines put the matter succinctly, stating, “The main departure from prior guidelines is that aspirin should not be used in AF simply to reduce the risk of stroke, as it is not as effective as NOACs [novel oral anticoagulants] ... and can cause more bleeding side effects.”

Dr. Gersh was coauthor of a recently published think piece that argued that exaggerated misperceptions of aspirin’s efficacy and safety have led to its inappropriate status as “the easy option” for stroke prevention in AF (Eur. Heart J. 2015;36:653-6).

“By giving physicians a soft option of aspirin in CHA₂DS₂-VASc 1 patients, we’re allowing them an excuse not to use an oral anticoagulant, which is what they should be using,” Dr. Gersh explained at the conference.

He noted that an analysis of more than 41,000 Medicare beneficiaries with AF in 2007-2008 showed that only 66.8% were on warfarin.

“There’s no doubt that warfarin, and for that matter the NOACs, are underutilized, and it’s possible that the misperception that aspirin is effective may contribute to that underutilization,” asserted Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

The cardiologist added that the widely held belief that aspirin reduces stroke risk by roughly 20%, compared with placebo, in patients with AF is based upon seriously flawed data. True, a meta-analysis of six placebo-controlled randomized trials done in an earlier era concluded that aspirin reduced the relative risk of stroke by 19%, but what’s often overlooked is that aspirin significantly outperformed placebo in only one of those six studies – the SPAF 1 trial – where in one arm aspirin achieved an “almost implausible” 94% relative risk reduction.

“Nothing reduces risk by 94%,” Dr. Gersh observed, adding that the SPAF 1 methodology was, upon careful examination, “completely unacceptable” by contemporary standards.

He was a coinvestigator in a study of 7,347 AF patients on oral anticoagulation therapy in 176 U.S. practices participating in the ORBIT-AF registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation). The analysis showed that concomitant use of aspirin and an oral anticoagulant in patients with AF is common in everyday clinical practice, being employed in 35% of the study population. Of note, 39% of these patients had no history of CAD and therefore weren’t on aspirin for secondary cardiovascular prevention, and 17% of them were at elevated bleeding risk because of an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more.

The key, disturbing finding was this: The adjusted risks of major bleeding and hospitalization for bleeding were 53% and 52% greater, respectively, in patients on an oral anticoagulant plus aspirin than with an oral anticoagulant alone (Circulation 2013;128:721-8).

On the basis of this study and other evidence, Dr. Gersh believes the use of aspirin in patients with AF should be considered only in those with CAD, where a case can be made for its use in secondary prevention alongside an oral anticoagulant to reduce stroke risk. But even then, aspirin’s use is reasonable only in those at low risk of bleeding, and extra vigilance and prophylaxis with a proton pump inhibitor are called for.

“If a patient is at high risk of bleeding, I personally would not give aspirin,” the cardiologist added.

The big remaining question – and an area of current controversy – concerns the safety of halting aspirin in AF patients on an oral anticoagulant who’ve undergone coronary stenting. Ongoing studies are looking at this issue, and answers are expected within a year or 2.

Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for Baxter, Medtronic, and Teva.

[email protected]

SNOWMASS, COLO.– The sun may be setting on the use of aspirin for thromboprophylaxis in patients with nonvalvular atrial fibrillation. The 2014 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines are unique among the major international guidelines in giving a modest IIb, Level of Evidence C endorsement to the option of aspirin or no treatment in patients with atrial fibrillation (AF) and a CHA₂DS₂-VASc score of 1. In contrast, the 2014 U.K. NICE (National Institute for Health and Care Excellence) guidelines, the 2013 Asian Pacific Heart Rhythm Society guidelines, and the 2012 European Society of Cardiology guidelines all recommend consideration of oral anticoagulation – eschewing aspirin – in patients with a CHA₂DS₂-VASc score of 1 or more, Dr. Bernard J. Gersh noted at the Annual Cardiovascular Conference at Snowmass.

The NICE guidelines put the matter succinctly, stating, “The main departure from prior guidelines is that aspirin should not be used in AF simply to reduce the risk of stroke, as it is not as effective as NOACs [novel oral anticoagulants] ... and can cause more bleeding side effects.”

Dr. Gersh was coauthor of a recently published think piece that argued that exaggerated misperceptions of aspirin’s efficacy and safety have led to its inappropriate status as “the easy option” for stroke prevention in AF (Eur. Heart J. 2015;36:653-6).

“By giving physicians a soft option of aspirin in CHA₂DS₂-VASc 1 patients, we’re allowing them an excuse not to use an oral anticoagulant, which is what they should be using,” Dr. Gersh explained at the conference.

He noted that an analysis of more than 41,000 Medicare beneficiaries with AF in 2007-2008 showed that only 66.8% were on warfarin.

“There’s no doubt that warfarin, and for that matter the NOACs, are underutilized, and it’s possible that the misperception that aspirin is effective may contribute to that underutilization,” asserted Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

The cardiologist added that the widely held belief that aspirin reduces stroke risk by roughly 20%, compared with placebo, in patients with AF is based upon seriously flawed data. True, a meta-analysis of six placebo-controlled randomized trials done in an earlier era concluded that aspirin reduced the relative risk of stroke by 19%, but what’s often overlooked is that aspirin significantly outperformed placebo in only one of those six studies – the SPAF 1 trial – where in one arm aspirin achieved an “almost implausible” 94% relative risk reduction.

“Nothing reduces risk by 94%,” Dr. Gersh observed, adding that the SPAF 1 methodology was, upon careful examination, “completely unacceptable” by contemporary standards.

He was a coinvestigator in a study of 7,347 AF patients on oral anticoagulation therapy in 176 U.S. practices participating in the ORBIT-AF registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation). The analysis showed that concomitant use of aspirin and an oral anticoagulant in patients with AF is common in everyday clinical practice, being employed in 35% of the study population. Of note, 39% of these patients had no history of CAD and therefore weren’t on aspirin for secondary cardiovascular prevention, and 17% of them were at elevated bleeding risk because of an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more.

The key, disturbing finding was this: The adjusted risks of major bleeding and hospitalization for bleeding were 53% and 52% greater, respectively, in patients on an oral anticoagulant plus aspirin than with an oral anticoagulant alone (Circulation 2013;128:721-8).

On the basis of this study and other evidence, Dr. Gersh believes the use of aspirin in patients with AF should be considered only in those with CAD, where a case can be made for its use in secondary prevention alongside an oral anticoagulant to reduce stroke risk. But even then, aspirin’s use is reasonable only in those at low risk of bleeding, and extra vigilance and prophylaxis with a proton pump inhibitor are called for.

“If a patient is at high risk of bleeding, I personally would not give aspirin,” the cardiologist added.

The big remaining question – and an area of current controversy – concerns the safety of halting aspirin in AF patients on an oral anticoagulant who’ve undergone coronary stenting. Ongoing studies are looking at this issue, and answers are expected within a year or 2.

Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for Baxter, Medtronic, and Teva.

[email protected]

SNOWMASS, COLO.– The sun may be setting on the use of aspirin for thromboprophylaxis in patients with nonvalvular atrial fibrillation. The 2014 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines are unique among the major international guidelines in giving a modest IIb, Level of Evidence C endorsement to the option of aspirin or no treatment in patients with atrial fibrillation (AF) and a CHA₂DS₂-VASc score of 1. In contrast, the 2014 U.K. NICE (National Institute for Health and Care Excellence) guidelines, the 2013 Asian Pacific Heart Rhythm Society guidelines, and the 2012 European Society of Cardiology guidelines all recommend consideration of oral anticoagulation – eschewing aspirin – in patients with a CHA₂DS₂-VASc score of 1 or more, Dr. Bernard J. Gersh noted at the Annual Cardiovascular Conference at Snowmass.

The NICE guidelines put the matter succinctly, stating, “The main departure from prior guidelines is that aspirin should not be used in AF simply to reduce the risk of stroke, as it is not as effective as NOACs [novel oral anticoagulants] ... and can cause more bleeding side effects.”

Dr. Gersh was coauthor of a recently published think piece that argued that exaggerated misperceptions of aspirin’s efficacy and safety have led to its inappropriate status as “the easy option” for stroke prevention in AF (Eur. Heart J. 2015;36:653-6).

“By giving physicians a soft option of aspirin in CHA₂DS₂-VASc 1 patients, we’re allowing them an excuse not to use an oral anticoagulant, which is what they should be using,” Dr. Gersh explained at the conference.

He noted that an analysis of more than 41,000 Medicare beneficiaries with AF in 2007-2008 showed that only 66.8% were on warfarin.

“There’s no doubt that warfarin, and for that matter the NOACs, are underutilized, and it’s possible that the misperception that aspirin is effective may contribute to that underutilization,” asserted Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

The cardiologist added that the widely held belief that aspirin reduces stroke risk by roughly 20%, compared with placebo, in patients with AF is based upon seriously flawed data. True, a meta-analysis of six placebo-controlled randomized trials done in an earlier era concluded that aspirin reduced the relative risk of stroke by 19%, but what’s often overlooked is that aspirin significantly outperformed placebo in only one of those six studies – the SPAF 1 trial – where in one arm aspirin achieved an “almost implausible” 94% relative risk reduction.

“Nothing reduces risk by 94%,” Dr. Gersh observed, adding that the SPAF 1 methodology was, upon careful examination, “completely unacceptable” by contemporary standards.

He was a coinvestigator in a study of 7,347 AF patients on oral anticoagulation therapy in 176 U.S. practices participating in the ORBIT-AF registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation). The analysis showed that concomitant use of aspirin and an oral anticoagulant in patients with AF is common in everyday clinical practice, being employed in 35% of the study population. Of note, 39% of these patients had no history of CAD and therefore weren’t on aspirin for secondary cardiovascular prevention, and 17% of them were at elevated bleeding risk because of an ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score of 5 or more.

The key, disturbing finding was this: The adjusted risks of major bleeding and hospitalization for bleeding were 53% and 52% greater, respectively, in patients on an oral anticoagulant plus aspirin than with an oral anticoagulant alone (Circulation 2013;128:721-8).

On the basis of this study and other evidence, Dr. Gersh believes the use of aspirin in patients with AF should be considered only in those with CAD, where a case can be made for its use in secondary prevention alongside an oral anticoagulant to reduce stroke risk. But even then, aspirin’s use is reasonable only in those at low risk of bleeding, and extra vigilance and prophylaxis with a proton pump inhibitor are called for.

“If a patient is at high risk of bleeding, I personally would not give aspirin,” the cardiologist added.

The big remaining question – and an area of current controversy – concerns the safety of halting aspirin in AF patients on an oral anticoagulant who’ve undergone coronary stenting. Ongoing studies are looking at this issue, and answers are expected within a year or 2.

Dr. Gersh reported serving as a consultant to Merck and Ortho-McNeil-Janssen and on data safety monitoring boards for Baxter, Medtronic, and Teva.

[email protected]

Why has teledermatology never taken off? Technically, we’ve been able to do it for years, yet most providers have been unwilling. This year, however, I expect we will cross the tipping point. The convergence of digital health records, expanding reimbursement, and consumerization of health care have led to a surge in demand, and now a supply of teledermatology services.

Much of this growth is from direct-to-consumer teledermatology providers. These are telehealth services marketed to patients where they access a dermatologist directly, paying out of pocket or with insurance. One such company is the aptly named Direct Dermatology.

Founded in 2009, it is an online dermatology clinic that provides 24/7 access to board-certified dermatologists. It is experiencing rapid growth and is currently looking to expand its network of dermatologists. For this month’s column, I share an interview with Dr. David Wong, cofounder of Direct Dermatology and clinical associate professor at Stanford (Calif.) University. I have no financial or other conflicts of interest to disclose.

Initially, telehealth was designed to serve rural communities with limited access to health care. Today it is used more widely. Would you share some examples of its use?

Dr. Wong: Much of the initial telehealth efforts and success have been in rural communities because telehealth solves a major problem of access to medical care in underserved areas. But it can be extremely valuable in all geographic areas, not just rural communities. Access is a problem even in urban areas, where wait time for a dermatologist appointment averages over 1 month. Telehealth has the potential to not only improve access, but also to improve quality of care and deliver care more efficiently for the patient, provider, and overall health system.

Teledermatology is being used by several employers as a benefit to their employees to provide convenient and timely access to dermatologists and decrease employee time away from work. There are several direct-to-consumer online teledermatology services that are being used by patients in all communities, especially urban communities.

The fact is that the majority of dermatology cases are seen by primary care physicians. If teledermatology can provide rapid, efficient, and reliable access to experienced dermatologists, the quality of dermatology care in the country will improve.

Please share some of the tangible benefits of teledermatology, such as triage, reducing the disparity in access to dermatologists, employer benefits, etc.

Another factor is that dermatology problems don’t occur only during business hours – we are seeing a growing number of cases submitted from our own patients over the weekend or in the evening. The ability to evaluate acutely developing skin problems within a few hours, such as rashes in children, can alleviate a lot of anxiety and avoid unnecessary emergency room costs.

Teledermatology also is beneficial to dermatologists in allowing us to provide care from anywhere on a flexible schedule. We don’t have to go into the office to “see” our patients. Both patient and provider satisfaction in our office’s teledermatology practice is very high.

Reimbursement has been a major drawback with telehealth. For example, Medicare reimburses for telemedicine services in some states, but others have restrictions. There are also more restrictions on the “store-and-forward” format than for the live, interactive format. Would you shed some light on this?

Dr. Wong: Yes, reimbursement has been a barrier to telehealth. But that is changing. A total of 22 states and the District of Columbia have passed parity laws for private insurance coverage of telemedicine, and 10 states have pending legislation. But whether telemedicine is actually covered by each health plan varies even in those 22 states. And coverage can vary depending on whether it is store-and-forward or live interactive teledermatology. Medicare still only covers store-and-forward teledermatology under a federal demonstration program in the states of Hawaii and Alaska. We believe that the ultimate driving force – delivery of high-quality and cost-effective specialty care to more patients – will continue to support the current trend in expanded telemedicine coverage.
 

What type of liability do dermatologists face when using telehealth?

Dr. Wong: The good news is that there have not been any malpractice lawsuits related to teledermatology to date. But physicians performing telehealth services should ensure that their malpractice liability insurance policy covers the exact form of telehealth that will be provided (just as it covers any other medical services that physicians provide), prior to starting to provide those services. Most medical malpractice insurance does not automatically cover telehealth services. In addition, be sure to understand state regulations about licensing, informed consent, and online prescribing.

How do patients feel about teledermatology? Do you notice any differences regarding patients’ gender and age?

Dr. Wong: I’m going to specifically speak about “store-and-forward” teledermatology, which is the predominant mode of teledermatology being used today. Store-and-forward teledermatology is an asynchronous mode where pictures of the skin problem and medical history are sent to the dermatologist. In general, patients love teledermatology. It is convenient; they don’t have to take time off from their busy schedules. They don’t have to wait for the next available appointment in my clinic. They can get answers and are placed on treatment that same day. In our practice, there is an opportunity for rapid, secure communication exchange with the dermatologist during the consultation as well. Of course, there are skeptics who wonder whether dermatologists can really make an accurate diagnosis with a picture. But once patients experience the service, they are typically very satisfied with what our dermatologists can do and with the quality of care. Anecdotally, we’re seeing a nearly equal distribution of male and female consumers seeking care through teledermatology. Individuals in their 30s comprise the largest age segment, but we see patients from all age groups, even pediatric cases sent by parents.

What do you say to physicians who are concerned that teledermatology will eventually replace in-person visits and erode the doctor-patient relationship?

Dr. Wong: Teledermatology will never completely replace in-person visits. But it will become an important component of our practices. Teledermatology can actually improve the doctor-patient relationship because it allows for increased connectivity between doctor and patient. It is important for dermatologists to define how teledermatology enhances our existing practices by improving the quality of care and actually strengthening our relationship with our patients.

What advice do you have for dermatologists who are considering implementing teledermatology in their practice?

Dr. Wong: Speak with other dermatologists who have had experience with providing teledermatology services in their practices. Learn from their best practices. In addition to adopting a new technology, think through how it incorporates into your clinic operations. And pay attention to regulatory and legal compliance in an environment where there is constant change.

What are your predictions for the future of teledermatology?

Dr. Wong: The future of teledermatology is exciting. It is now an important tool to provide even better care to our patients. The technology for high-quality photography from mobile devices has rapidly advanced, and in most cases, when done properly, the resulting images are as good as – or better than – what you can see with the unaided human eye in an exam room. Because of the way our field has thoughtfully implemented teledermatology alongside traditional dermatology, teledermatology will very soon become a standard of care. The term “teledermatology” will no longer be used because it will simply be a standard part of dermatology practice.

For more information and contacts, please visit DirectDermatology.com.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. Dr. Benabio is @dermdoc on Twitter.

Why has teledermatology never taken off? Technically, we’ve been able to do it for years, yet most providers have been unwilling. This year, however, I expect we will cross the tipping point. The convergence of digital health records, expanding reimbursement, and consumerization of health care have led to a surge in demand, and now a supply of teledermatology services.

Much of this growth is from direct-to-consumer teledermatology providers. These are telehealth services marketed to patients where they access a dermatologist directly, paying out of pocket or with insurance. One such company is the aptly named Direct Dermatology.

Founded in 2009, it is an online dermatology clinic that provides 24/7 access to board-certified dermatologists. It is experiencing rapid growth and is currently looking to expand its network of dermatologists. For this month’s column, I share an interview with Dr. David Wong, cofounder of Direct Dermatology and clinical associate professor at Stanford (Calif.) University. I have no financial or other conflicts of interest to disclose.

Initially, telehealth was designed to serve rural communities with limited access to health care. Today it is used more widely. Would you share some examples of its use?

Dr. Wong: Much of the initial telehealth efforts and success have been in rural communities because telehealth solves a major problem of access to medical care in underserved areas. But it can be extremely valuable in all geographic areas, not just rural communities. Access is a problem even in urban areas, where wait time for a dermatologist appointment averages over 1 month. Telehealth has the potential to not only improve access, but also to improve quality of care and deliver care more efficiently for the patient, provider, and overall health system.

Teledermatology is being used by several employers as a benefit to their employees to provide convenient and timely access to dermatologists and decrease employee time away from work. There are several direct-to-consumer online teledermatology services that are being used by patients in all communities, especially urban communities.

The fact is that the majority of dermatology cases are seen by primary care physicians. If teledermatology can provide rapid, efficient, and reliable access to experienced dermatologists, the quality of dermatology care in the country will improve.

Please share some of the tangible benefits of teledermatology, such as triage, reducing the disparity in access to dermatologists, employer benefits, etc.

Another factor is that dermatology problems don’t occur only during business hours – we are seeing a growing number of cases submitted from our own patients over the weekend or in the evening. The ability to evaluate acutely developing skin problems within a few hours, such as rashes in children, can alleviate a lot of anxiety and avoid unnecessary emergency room costs.

Teledermatology also is beneficial to dermatologists in allowing us to provide care from anywhere on a flexible schedule. We don’t have to go into the office to “see” our patients. Both patient and provider satisfaction in our office’s teledermatology practice is very high.

Reimbursement has been a major drawback with telehealth. For example, Medicare reimburses for telemedicine services in some states, but others have restrictions. There are also more restrictions on the “store-and-forward” format than for the live, interactive format. Would you shed some light on this?

Dr. Wong: Yes, reimbursement has been a barrier to telehealth. But that is changing. A total of 22 states and the District of Columbia have passed parity laws for private insurance coverage of telemedicine, and 10 states have pending legislation. But whether telemedicine is actually covered by each health plan varies even in those 22 states. And coverage can vary depending on whether it is store-and-forward or live interactive teledermatology. Medicare still only covers store-and-forward teledermatology under a federal demonstration program in the states of Hawaii and Alaska. We believe that the ultimate driving force – delivery of high-quality and cost-effective specialty care to more patients – will continue to support the current trend in expanded telemedicine coverage.
 

What type of liability do dermatologists face when using telehealth?

Dr. Wong: The good news is that there have not been any malpractice lawsuits related to teledermatology to date. But physicians performing telehealth services should ensure that their malpractice liability insurance policy covers the exact form of telehealth that will be provided (just as it covers any other medical services that physicians provide), prior to starting to provide those services. Most medical malpractice insurance does not automatically cover telehealth services. In addition, be sure to understand state regulations about licensing, informed consent, and online prescribing.

How do patients feel about teledermatology? Do you notice any differences regarding patients’ gender and age?

Dr. Wong: I’m going to specifically speak about “store-and-forward” teledermatology, which is the predominant mode of teledermatology being used today. Store-and-forward teledermatology is an asynchronous mode where pictures of the skin problem and medical history are sent to the dermatologist. In general, patients love teledermatology. It is convenient; they don’t have to take time off from their busy schedules. They don’t have to wait for the next available appointment in my clinic. They can get answers and are placed on treatment that same day. In our practice, there is an opportunity for rapid, secure communication exchange with the dermatologist during the consultation as well. Of course, there are skeptics who wonder whether dermatologists can really make an accurate diagnosis with a picture. But once patients experience the service, they are typically very satisfied with what our dermatologists can do and with the quality of care. Anecdotally, we’re seeing a nearly equal distribution of male and female consumers seeking care through teledermatology. Individuals in their 30s comprise the largest age segment, but we see patients from all age groups, even pediatric cases sent by parents.

What do you say to physicians who are concerned that teledermatology will eventually replace in-person visits and erode the doctor-patient relationship?

Dr. Wong: Teledermatology will never completely replace in-person visits. But it will become an important component of our practices. Teledermatology can actually improve the doctor-patient relationship because it allows for increased connectivity between doctor and patient. It is important for dermatologists to define how teledermatology enhances our existing practices by improving the quality of care and actually strengthening our relationship with our patients.

What advice do you have for dermatologists who are considering implementing teledermatology in their practice?

Dr. Wong: Speak with other dermatologists who have had experience with providing teledermatology services in their practices. Learn from their best practices. In addition to adopting a new technology, think through how it incorporates into your clinic operations. And pay attention to regulatory and legal compliance in an environment where there is constant change.

What are your predictions for the future of teledermatology?

Dr. Wong: The future of teledermatology is exciting. It is now an important tool to provide even better care to our patients. The technology for high-quality photography from mobile devices has rapidly advanced, and in most cases, when done properly, the resulting images are as good as – or better than – what you can see with the unaided human eye in an exam room. Because of the way our field has thoughtfully implemented teledermatology alongside traditional dermatology, teledermatology will very soon become a standard of care. The term “teledermatology” will no longer be used because it will simply be a standard part of dermatology practice.

For more information and contacts, please visit DirectDermatology.com.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. Dr. Benabio is @dermdoc on Twitter.

Why has teledermatology never taken off? Technically, we’ve been able to do it for years, yet most providers have been unwilling. This year, however, I expect we will cross the tipping point. The convergence of digital health records, expanding reimbursement, and consumerization of health care have led to a surge in demand, and now a supply of teledermatology services.

Much of this growth is from direct-to-consumer teledermatology providers. These are telehealth services marketed to patients where they access a dermatologist directly, paying out of pocket or with insurance. One such company is the aptly named Direct Dermatology.

Founded in 2009, it is an online dermatology clinic that provides 24/7 access to board-certified dermatologists. It is experiencing rapid growth and is currently looking to expand its network of dermatologists. For this month’s column, I share an interview with Dr. David Wong, cofounder of Direct Dermatology and clinical associate professor at Stanford (Calif.) University. I have no financial or other conflicts of interest to disclose.

Initially, telehealth was designed to serve rural communities with limited access to health care. Today it is used more widely. Would you share some examples of its use?

Dr. Wong: Much of the initial telehealth efforts and success have been in rural communities because telehealth solves a major problem of access to medical care in underserved areas. But it can be extremely valuable in all geographic areas, not just rural communities. Access is a problem even in urban areas, where wait time for a dermatologist appointment averages over 1 month. Telehealth has the potential to not only improve access, but also to improve quality of care and deliver care more efficiently for the patient, provider, and overall health system.

Teledermatology is being used by several employers as a benefit to their employees to provide convenient and timely access to dermatologists and decrease employee time away from work. There are several direct-to-consumer online teledermatology services that are being used by patients in all communities, especially urban communities.

The fact is that the majority of dermatology cases are seen by primary care physicians. If teledermatology can provide rapid, efficient, and reliable access to experienced dermatologists, the quality of dermatology care in the country will improve.

Please share some of the tangible benefits of teledermatology, such as triage, reducing the disparity in access to dermatologists, employer benefits, etc.

Another factor is that dermatology problems don’t occur only during business hours – we are seeing a growing number of cases submitted from our own patients over the weekend or in the evening. The ability to evaluate acutely developing skin problems within a few hours, such as rashes in children, can alleviate a lot of anxiety and avoid unnecessary emergency room costs.

Teledermatology also is beneficial to dermatologists in allowing us to provide care from anywhere on a flexible schedule. We don’t have to go into the office to “see” our patients. Both patient and provider satisfaction in our office’s teledermatology practice is very high.

Reimbursement has been a major drawback with telehealth. For example, Medicare reimburses for telemedicine services in some states, but others have restrictions. There are also more restrictions on the “store-and-forward” format than for the live, interactive format. Would you shed some light on this?

Dr. Wong: Yes, reimbursement has been a barrier to telehealth. But that is changing. A total of 22 states and the District of Columbia have passed parity laws for private insurance coverage of telemedicine, and 10 states have pending legislation. But whether telemedicine is actually covered by each health plan varies even in those 22 states. And coverage can vary depending on whether it is store-and-forward or live interactive teledermatology. Medicare still only covers store-and-forward teledermatology under a federal demonstration program in the states of Hawaii and Alaska. We believe that the ultimate driving force – delivery of high-quality and cost-effective specialty care to more patients – will continue to support the current trend in expanded telemedicine coverage.
 

What type of liability do dermatologists face when using telehealth?

Dr. Wong: The good news is that there have not been any malpractice lawsuits related to teledermatology to date. But physicians performing telehealth services should ensure that their malpractice liability insurance policy covers the exact form of telehealth that will be provided (just as it covers any other medical services that physicians provide), prior to starting to provide those services. Most medical malpractice insurance does not automatically cover telehealth services. In addition, be sure to understand state regulations about licensing, informed consent, and online prescribing.

How do patients feel about teledermatology? Do you notice any differences regarding patients’ gender and age?

Dr. Wong: I’m going to specifically speak about “store-and-forward” teledermatology, which is the predominant mode of teledermatology being used today. Store-and-forward teledermatology is an asynchronous mode where pictures of the skin problem and medical history are sent to the dermatologist. In general, patients love teledermatology. It is convenient; they don’t have to take time off from their busy schedules. They don’t have to wait for the next available appointment in my clinic. They can get answers and are placed on treatment that same day. In our practice, there is an opportunity for rapid, secure communication exchange with the dermatologist during the consultation as well. Of course, there are skeptics who wonder whether dermatologists can really make an accurate diagnosis with a picture. But once patients experience the service, they are typically very satisfied with what our dermatologists can do and with the quality of care. Anecdotally, we’re seeing a nearly equal distribution of male and female consumers seeking care through teledermatology. Individuals in their 30s comprise the largest age segment, but we see patients from all age groups, even pediatric cases sent by parents.

What do you say to physicians who are concerned that teledermatology will eventually replace in-person visits and erode the doctor-patient relationship?

Dr. Wong: Teledermatology will never completely replace in-person visits. But it will become an important component of our practices. Teledermatology can actually improve the doctor-patient relationship because it allows for increased connectivity between doctor and patient. It is important for dermatologists to define how teledermatology enhances our existing practices by improving the quality of care and actually strengthening our relationship with our patients.

What advice do you have for dermatologists who are considering implementing teledermatology in their practice?

Dr. Wong: Speak with other dermatologists who have had experience with providing teledermatology services in their practices. Learn from their best practices. In addition to adopting a new technology, think through how it incorporates into your clinic operations. And pay attention to regulatory and legal compliance in an environment where there is constant change.

What are your predictions for the future of teledermatology?

Dr. Wong: The future of teledermatology is exciting. It is now an important tool to provide even better care to our patients. The technology for high-quality photography from mobile devices has rapidly advanced, and in most cases, when done properly, the resulting images are as good as – or better than – what you can see with the unaided human eye in an exam room. Because of the way our field has thoughtfully implemented teledermatology alongside traditional dermatology, teledermatology will very soon become a standard of care. The term “teledermatology” will no longer be used because it will simply be a standard part of dermatology practice.

For more information and contacts, please visit DirectDermatology.com.

Dr. Benabio is a partner physician in the department of dermatology of the Southern California Permanente Group in San Diego, and a volunteer clinical assistant professor at the University of California, San Diego. Dr. Benabio is @dermdoc on Twitter.

Three women hospitalists, Dr. Danielle Scheurer, chief quality officer at the Medical University of South Carolina; Dr. Sowmya Kanikkannan, hospital medicine director and assistant professor of medicine at Rowan University School of Osteopathic Medicine; and Dr. Vineet Arora, assistant dean at the University of Chicago School of Medicine, discuss the state of gender equity in hospital medicine and offer tips for women seeking careers in HM.

Three women hospitalists, Dr. Danielle Scheurer, chief quality officer at the Medical University of South Carolina; Dr. Sowmya Kanikkannan, hospital medicine director and assistant professor of medicine at Rowan University School of Osteopathic Medicine; and Dr. Vineet Arora, assistant dean at the University of Chicago School of Medicine, discuss the state of gender equity in hospital medicine and offer tips for women seeking careers in HM.

Three women hospitalists, Dr. Danielle Scheurer, chief quality officer at the Medical University of South Carolina; Dr. Sowmya Kanikkannan, hospital medicine director and assistant professor of medicine at Rowan University School of Osteopathic Medicine; and Dr. Vineet Arora, assistant dean at the University of Chicago School of Medicine, discuss the state of gender equity in hospital medicine and offer tips for women seeking careers in HM.

When I last wrote about the International Classification of Diseases, 10th Revision (ICD-10) – last year, at about this time – the switchover was scheduled to take place on Oct. 1. Shortly thereafter, of course, Congress decided to delay the inevitable for 1 year. While the House Energy and Commerce Committee has hinted at the possibility of further postponements, we must all assume, until we hear otherwise, that the day of reckoning will arrive as scheduled. You will need to be ready if you expect to be paid come October.

Remember, on Sept. 30 you will be using ICD-9 codes, and the next day you will have to begin using ICD-10. There is no transition period; all ICD-9–coded claims will be rejected from Oct. 1 forward, and no ICD-10 codes can be used before that date. Failure to prepare will be an unmitigated disaster for your practice’s cash flow.

First, decide which parts of your coding and billing systems – and EHR, if you have one – need to be upgraded, how you will do it, and what it will cost. Then, you must get familiar with the new system.

Coders and billers will need the most training on the new methodology, but physicians and other providers must also learn how the new codes are different from the old ones. In general, most differences are in specificity and level of documentation (left/right, acute/chronic, etc.), but there are new codes as well.

I suggest you start by identifying your most-used 20 or 30 diagnosis codes, and then study in detail the differences between the ICD-9 and ICD-10 versions of them. Once you have mastered those, you can go on to other, less-used codes. Take as much time as you need to do this: Remember, everything changes abruptly on Oct. 1, and you will have to get it right the first time.

Be sure to cross-train your coders and other staff members. If a crucial employee quits in the middle of September, you don’t want to have to start from square one. Also, ask your employees to plan their vacations well in advance – and not during the last 3 months of the year. That goes for you, too. This will not be a good time for you to be away, or for the office to run short-staffed.

Next, I suggest you contact all of your third-party payers, billing services, and clearinghouses. Be aggressive; ask them how, exactly, they are preparing for the changeover, and stay in continuous contact with them. Unfortunately, many of these organizations are as behind as most medical practices in their preparations.

Many payers and clearinghouses (including the Centers for Medicare & Medicaid Services) are staging test runs during which you can submit practice claims using the new system. Payers will determine whether your ICD-10 code is in the right place and in the right format; whether the code you used is appropriate; and whether the claim would have been accepted, rejected, or held pending additional information. You will need to do this for each payer, because each will have different coding policies. Many of those policies have not yet been released, and, in some cases, have not even been developed.

You can register for CMS testing sessions through your local Medicare Administrative Contractor (MAC) website. Use the sessions to test your internal system as well, to ensure that everything works smoothly from the time you code a claim until payment is received. Select commonly used ICD-9 claims and practice coding them in ICD-10. The American Academy of Dermatology offers an assortment of training aids at its website, aad.org.

Even the best-laid plans can go awry, however, so it would be prudent to put aside a cash reserve or secure a line of credit to cover expenses during the first few months of the transition, in case the payment machinery falters and large numbers of claims go unpaid. For the same reason, consider postponing major capital investments until early 2016.

You may have heard that ICD-10 is only a transition system; that ICD-11 will be following closely on its heels. I doubt it. In all probability, we will be using ICD-10 a lot longer than CMS originally planned. Besides, ICD-11 is essentially a refinement of ICD-10, not the significant departure that the 10th revision is over the 9th.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News.

When I last wrote about the International Classification of Diseases, 10th Revision (ICD-10) – last year, at about this time – the switchover was scheduled to take place on Oct. 1. Shortly thereafter, of course, Congress decided to delay the inevitable for 1 year. While the House Energy and Commerce Committee has hinted at the possibility of further postponements, we must all assume, until we hear otherwise, that the day of reckoning will arrive as scheduled. You will need to be ready if you expect to be paid come October.

Remember, on Sept. 30 you will be using ICD-9 codes, and the next day you will have to begin using ICD-10. There is no transition period; all ICD-9–coded claims will be rejected from Oct. 1 forward, and no ICD-10 codes can be used before that date. Failure to prepare will be an unmitigated disaster for your practice’s cash flow.

First, decide which parts of your coding and billing systems – and EHR, if you have one – need to be upgraded, how you will do it, and what it will cost. Then, you must get familiar with the new system.

Coders and billers will need the most training on the new methodology, but physicians and other providers must also learn how the new codes are different from the old ones. In general, most differences are in specificity and level of documentation (left/right, acute/chronic, etc.), but there are new codes as well.

I suggest you start by identifying your most-used 20 or 30 diagnosis codes, and then study in detail the differences between the ICD-9 and ICD-10 versions of them. Once you have mastered those, you can go on to other, less-used codes. Take as much time as you need to do this: Remember, everything changes abruptly on Oct. 1, and you will have to get it right the first time.

Be sure to cross-train your coders and other staff members. If a crucial employee quits in the middle of September, you don’t want to have to start from square one. Also, ask your employees to plan their vacations well in advance – and not during the last 3 months of the year. That goes for you, too. This will not be a good time for you to be away, or for the office to run short-staffed.

Next, I suggest you contact all of your third-party payers, billing services, and clearinghouses. Be aggressive; ask them how, exactly, they are preparing for the changeover, and stay in continuous contact with them. Unfortunately, many of these organizations are as behind as most medical practices in their preparations.

Many payers and clearinghouses (including the Centers for Medicare & Medicaid Services) are staging test runs during which you can submit practice claims using the new system. Payers will determine whether your ICD-10 code is in the right place and in the right format; whether the code you used is appropriate; and whether the claim would have been accepted, rejected, or held pending additional information. You will need to do this for each payer, because each will have different coding policies. Many of those policies have not yet been released, and, in some cases, have not even been developed.

You can register for CMS testing sessions through your local Medicare Administrative Contractor (MAC) website. Use the sessions to test your internal system as well, to ensure that everything works smoothly from the time you code a claim until payment is received. Select commonly used ICD-9 claims and practice coding them in ICD-10. The American Academy of Dermatology offers an assortment of training aids at its website, aad.org.

Even the best-laid plans can go awry, however, so it would be prudent to put aside a cash reserve or secure a line of credit to cover expenses during the first few months of the transition, in case the payment machinery falters and large numbers of claims go unpaid. For the same reason, consider postponing major capital investments until early 2016.

You may have heard that ICD-10 is only a transition system; that ICD-11 will be following closely on its heels. I doubt it. In all probability, we will be using ICD-10 a lot longer than CMS originally planned. Besides, ICD-11 is essentially a refinement of ICD-10, not the significant departure that the 10th revision is over the 9th.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News.

When I last wrote about the International Classification of Diseases, 10th Revision (ICD-10) – last year, at about this time – the switchover was scheduled to take place on Oct. 1. Shortly thereafter, of course, Congress decided to delay the inevitable for 1 year. While the House Energy and Commerce Committee has hinted at the possibility of further postponements, we must all assume, until we hear otherwise, that the day of reckoning will arrive as scheduled. You will need to be ready if you expect to be paid come October.

Remember, on Sept. 30 you will be using ICD-9 codes, and the next day you will have to begin using ICD-10. There is no transition period; all ICD-9–coded claims will be rejected from Oct. 1 forward, and no ICD-10 codes can be used before that date. Failure to prepare will be an unmitigated disaster for your practice’s cash flow.

First, decide which parts of your coding and billing systems – and EHR, if you have one – need to be upgraded, how you will do it, and what it will cost. Then, you must get familiar with the new system.

Coders and billers will need the most training on the new methodology, but physicians and other providers must also learn how the new codes are different from the old ones. In general, most differences are in specificity and level of documentation (left/right, acute/chronic, etc.), but there are new codes as well.

I suggest you start by identifying your most-used 20 or 30 diagnosis codes, and then study in detail the differences between the ICD-9 and ICD-10 versions of them. Once you have mastered those, you can go on to other, less-used codes. Take as much time as you need to do this: Remember, everything changes abruptly on Oct. 1, and you will have to get it right the first time.

Be sure to cross-train your coders and other staff members. If a crucial employee quits in the middle of September, you don’t want to have to start from square one. Also, ask your employees to plan their vacations well in advance – and not during the last 3 months of the year. That goes for you, too. This will not be a good time for you to be away, or for the office to run short-staffed.

Next, I suggest you contact all of your third-party payers, billing services, and clearinghouses. Be aggressive; ask them how, exactly, they are preparing for the changeover, and stay in continuous contact with them. Unfortunately, many of these organizations are as behind as most medical practices in their preparations.

Many payers and clearinghouses (including the Centers for Medicare & Medicaid Services) are staging test runs during which you can submit practice claims using the new system. Payers will determine whether your ICD-10 code is in the right place and in the right format; whether the code you used is appropriate; and whether the claim would have been accepted, rejected, or held pending additional information. You will need to do this for each payer, because each will have different coding policies. Many of those policies have not yet been released, and, in some cases, have not even been developed.

You can register for CMS testing sessions through your local Medicare Administrative Contractor (MAC) website. Use the sessions to test your internal system as well, to ensure that everything works smoothly from the time you code a claim until payment is received. Select commonly used ICD-9 claims and practice coding them in ICD-10. The American Academy of Dermatology offers an assortment of training aids at its website, aad.org.

Even the best-laid plans can go awry, however, so it would be prudent to put aside a cash reserve or secure a line of credit to cover expenses during the first few months of the transition, in case the payment machinery falters and large numbers of claims go unpaid. For the same reason, consider postponing major capital investments until early 2016.

You may have heard that ICD-10 is only a transition system; that ICD-11 will be following closely on its heels. I doubt it. In all probability, we will be using ICD-10 a lot longer than CMS originally planned. Besides, ICD-11 is essentially a refinement of ICD-10, not the significant departure that the 10th revision is over the 9th.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News.

Patient consults pharmacist

Photo by Rhoda Baer

Pharmacists can greatly improve patients’ adherence to the anticoagulant dabigatran, according to a study published in JAMA.

When patients with atrial fibrillation had their dabigatran prescriptions filled by pharmacists who educated them about the drug and monitored them on a regular basis, these individuals were 80% more likely to adhere to medication guidelines than patients who didn’t receive this kind of support.

“Although pharmacist-led management of [dabigatran and other new oral anticoagulants] is uncommon in the US, the findings make the case that it is still important and can ultimately impact clinical outcomes,” said study author Mintu Turakhia, MD, of Stanford University School of Medicine in California.

Previous studies had suggested that some patients were not adhering well to treatment guidelines for dabigatran. So Dr Turakhia and his colleagues set out to determine if this lack of adherence could be explained by where patients were filling their prescriptions.

The team looked at Veterans Health Administration sites where 20 or more outpatients had dabigatran prescriptions filled between 2010 and 2012.

“Surprisingly, we found that treatment adherence varied not by individual, but by site,” Dr Turakhia said. “We didn’t expect to see that much variation by site.”

So the researchers conducted in-depth telephone interviews with the managers, usually pharmacists, at 41 of these sites.

“We rolled up our sleeves and looked at what each site was doing,” Dr Turakhia said.

At the sites with the highest patient adherence, there was usually a pharmacist actively educating patients on medication adherence, reviewing any possible drug interactions, and following up to make sure patients were taking the medication when they were supposed to and that prescriptions were being refilled on time.

The sites with patients who had the highest adherence levels had some key features in common, among them this type of “pharmacist-led patient management.”

“We determined there was a high level of scrutiny and review to make sure patients were getting the drugs,” Dr Turakhia said. “There was a lot of consideration of the dose, interaction with chronic kidney disease, and review to make sure that patients should be getting these drugs.”

These results suggest an unintended side effect of atrial fibrillation patients switching from warfarin to dabigatran or other new oral anticoagulants may be poorer adherence to medication guidelines because most patients no longer make routine visits to a lab for monitoring.

“This finding challenges the entire framework of healthcare delivery of these new agents,” Dr Turakhia said. “These medicines were pitched as easier for patients and for healthcare providers.”

Since patients on new oral anticoagulants are no longer required to visit labs regularly, in most cases, the physician and/or practice nurses are responsible for checking on adherence. And most doctors’ offices don’t have a system in place to verify how well patients take their medication or get patients their refills promptly before medications run out.

“We’re suggesting that greater structured management of these patients, beyond the doctor just prescribing medications for them, is a good idea,” Dr Turakhia said. “Extra support, like that provided in the VA anticoagulation clinics with supportive pharmacist care, greatly improves medication adherence.”

Patient consults pharmacist

Photo by Rhoda Baer

Pharmacists can greatly improve patients’ adherence to the anticoagulant dabigatran, according to a study published in JAMA.

When patients with atrial fibrillation had their dabigatran prescriptions filled by pharmacists who educated them about the drug and monitored them on a regular basis, these individuals were 80% more likely to adhere to medication guidelines than patients who didn’t receive this kind of support.

“Although pharmacist-led management of [dabigatran and other new oral anticoagulants] is uncommon in the US, the findings make the case that it is still important and can ultimately impact clinical outcomes,” said study author Mintu Turakhia, MD, of Stanford University School of Medicine in California.

Previous studies had suggested that some patients were not adhering well to treatment guidelines for dabigatran. So Dr Turakhia and his colleagues set out to determine if this lack of adherence could be explained by where patients were filling their prescriptions.

The team looked at Veterans Health Administration sites where 20 or more outpatients had dabigatran prescriptions filled between 2010 and 2012.

“Surprisingly, we found that treatment adherence varied not by individual, but by site,” Dr Turakhia said. “We didn’t expect to see that much variation by site.”

So the researchers conducted in-depth telephone interviews with the managers, usually pharmacists, at 41 of these sites.

“We rolled up our sleeves and looked at what each site was doing,” Dr Turakhia said.

At the sites with the highest patient adherence, there was usually a pharmacist actively educating patients on medication adherence, reviewing any possible drug interactions, and following up to make sure patients were taking the medication when they were supposed to and that prescriptions were being refilled on time.

The sites with patients who had the highest adherence levels had some key features in common, among them this type of “pharmacist-led patient management.”

“We determined there was a high level of scrutiny and review to make sure patients were getting the drugs,” Dr Turakhia said. “There was a lot of consideration of the dose, interaction with chronic kidney disease, and review to make sure that patients should be getting these drugs.”

These results suggest an unintended side effect of atrial fibrillation patients switching from warfarin to dabigatran or other new oral anticoagulants may be poorer adherence to medication guidelines because most patients no longer make routine visits to a lab for monitoring.

“This finding challenges the entire framework of healthcare delivery of these new agents,” Dr Turakhia said. “These medicines were pitched as easier for patients and for healthcare providers.”

Since patients on new oral anticoagulants are no longer required to visit labs regularly, in most cases, the physician and/or practice nurses are responsible for checking on adherence. And most doctors’ offices don’t have a system in place to verify how well patients take their medication or get patients their refills promptly before medications run out.

“We’re suggesting that greater structured management of these patients, beyond the doctor just prescribing medications for them, is a good idea,” Dr Turakhia said. “Extra support, like that provided in the VA anticoagulation clinics with supportive pharmacist care, greatly improves medication adherence.”

Patient consults pharmacist

Photo by Rhoda Baer

Pharmacists can greatly improve patients’ adherence to the anticoagulant dabigatran, according to a study published in JAMA.

When patients with atrial fibrillation had their dabigatran prescriptions filled by pharmacists who educated them about the drug and monitored them on a regular basis, these individuals were 80% more likely to adhere to medication guidelines than patients who didn’t receive this kind of support.

“Although pharmacist-led management of [dabigatran and other new oral anticoagulants] is uncommon in the US, the findings make the case that it is still important and can ultimately impact clinical outcomes,” said study author Mintu Turakhia, MD, of Stanford University School of Medicine in California.

Previous studies had suggested that some patients were not adhering well to treatment guidelines for dabigatran. So Dr Turakhia and his colleagues set out to determine if this lack of adherence could be explained by where patients were filling their prescriptions.

The team looked at Veterans Health Administration sites where 20 or more outpatients had dabigatran prescriptions filled between 2010 and 2012.

“Surprisingly, we found that treatment adherence varied not by individual, but by site,” Dr Turakhia said. “We didn’t expect to see that much variation by site.”

So the researchers conducted in-depth telephone interviews with the managers, usually pharmacists, at 41 of these sites.

“We rolled up our sleeves and looked at what each site was doing,” Dr Turakhia said.

At the sites with the highest patient adherence, there was usually a pharmacist actively educating patients on medication adherence, reviewing any possible drug interactions, and following up to make sure patients were taking the medication when they were supposed to and that prescriptions were being refilled on time.

The sites with patients who had the highest adherence levels had some key features in common, among them this type of “pharmacist-led patient management.”

“We determined there was a high level of scrutiny and review to make sure patients were getting the drugs,” Dr Turakhia said. “There was a lot of consideration of the dose, interaction with chronic kidney disease, and review to make sure that patients should be getting these drugs.”

These results suggest an unintended side effect of atrial fibrillation patients switching from warfarin to dabigatran or other new oral anticoagulants may be poorer adherence to medication guidelines because most patients no longer make routine visits to a lab for monitoring.

“This finding challenges the entire framework of healthcare delivery of these new agents,” Dr Turakhia said. “These medicines were pitched as easier for patients and for healthcare providers.”

Since patients on new oral anticoagulants are no longer required to visit labs regularly, in most cases, the physician and/or practice nurses are responsible for checking on adherence. And most doctors’ offices don’t have a system in place to verify how well patients take their medication or get patients their refills promptly before medications run out.

“We’re suggesting that greater structured management of these patients, beyond the doctor just prescribing medications for them, is a good idea,” Dr Turakhia said. “Extra support, like that provided in the VA anticoagulation clinics with supportive pharmacist care, greatly improves medication adherence.”

Micrograph showing APL

Image courtesy of AFIP

New research suggests the vitamin A derivative all-trans retinoic acid (ATRA) inhibits multiple oncogenic pathways and, at the same time, eliminates cancer stem cells by degrading the Pin1 enzyme.

Investigators said this discovery explains how ATRA successfully treats acute promyelocytic leukemia (APL), and it likely has implications for the treatment of other aggressive or drug-resistant cancers.

The team detailed their discovery in Nature Medicine.

“Pin1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease,” said study author Kun Ping Lu, MD, PhD, of Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, Massachusetts.

“Pin1 is a common, key regulator in many types of cancer and, as a result, can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells.”

Until now, agents that inhibit Pin1 have been developed mainly through rational drug design. These inhibitors have proven active against Pin1 in the test tube, but, when tested in a cell model or in vivo, they are unable to efficiently enter cells to successfully inhibit Pin1 function.

In this new work, the investigators decided to take a different approach to identify Pin1 inhibitors. They developed a mechanism-based, high-throughput screen to identify compounds that were targeting active Pin1.

“We had previously identified Pin1 substrate-mimicking peptide inhibitors,” said Xiao Zhen Zhou, MD, also of Beth Israel Deaconess Medical Center.

“We therefore used these as a probe in a competition binding assay and screened approximately 8200 chemical compounds, including both approved drugs and other known bioactive compounds.”

To increase screening success, the investigators chose a probe that specifically binds to the Pin1 enzyme active site very tightly, an approach that is not commonly used for this kind of screen.

“Initially, it appeared that the screening results had no positive hits, so we had to manually sift through them looking for the one that would bind to Pin1,” Dr Zhou said. “We eventually spotted cis retinoic acid, which has the same chemical formula as all-trans retinoic acid but with a different chemical structure.”

It turned out that Pin1 prefers binding to ATRA, and cis retinoic acid needs to convert to ATRA in order to bind Pin1.

ATRA in APL and other cancers

ATRA was first discovered for the treatment of APL in 1987. It was originally thought that ATRA was treating APL by inducing cell differentiation, causing cancer cells to change into normal cells by activating the cellular retinoic acid receptors.

But these new findings suggest that is not the mechanism that is actually behind ATRA’s successful outcomes in treating APL.

“While it has been previously shown that ATRA’s ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL, the underlying mechanism has remained elusive,” Dr Lu said.

“Our new, high-throughput drug screening has revealed the ATRA drug target, unexpectedly showing that ATRA directly binds, inhibits, and ultimately degrades active Pin1 selectively in cancer cells. The Pin1-ATRA complex structure suggests that ATRA is trapped in the Pin1 active site by mimicking an unreleasable enzyme substrate. Importantly, ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RAR and treats APL in cell and animal models as well as in human patients.”

The investigators discovered that ATRA-induced Pin1 ablation inhibits triple-negative breast cancer growth as well. The drug proved active in human cells and in animal models, simultaneously turning off many oncogenes and turning on many tumor suppressors.

The team said these results provide a rationale for trying to extend ATRA’s half-life and for developing more potent, Pin1-targeted ATRA variants for cancer treatment.

“The current ATRA drug has a very short half-life of only 45 minutes in humans,” Dr Lu said. “We think that a more potent Pin1 inhibitor will be able to target many ‘dream targets’ that are not currently druggable.”

“ATRA appears to be well tolerated, with minimal side effects, and offers a promising new approach for targeting a Pin1-dependent, common oncogenic mechanism in numerous cancer-driving pathways in cancer and cancer stem cells. This is especially critical for treating aggressive or drug-resistant cancers.”

Micrograph showing APL

Image courtesy of AFIP

New research suggests the vitamin A derivative all-trans retinoic acid (ATRA) inhibits multiple oncogenic pathways and, at the same time, eliminates cancer stem cells by degrading the Pin1 enzyme.

Investigators said this discovery explains how ATRA successfully treats acute promyelocytic leukemia (APL), and it likely has implications for the treatment of other aggressive or drug-resistant cancers.

The team detailed their discovery in Nature Medicine.

“Pin1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease,” said study author Kun Ping Lu, MD, PhD, of Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, Massachusetts.

“Pin1 is a common, key regulator in many types of cancer and, as a result, can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells.”

Until now, agents that inhibit Pin1 have been developed mainly through rational drug design. These inhibitors have proven active against Pin1 in the test tube, but, when tested in a cell model or in vivo, they are unable to efficiently enter cells to successfully inhibit Pin1 function.

In this new work, the investigators decided to take a different approach to identify Pin1 inhibitors. They developed a mechanism-based, high-throughput screen to identify compounds that were targeting active Pin1.

“We had previously identified Pin1 substrate-mimicking peptide inhibitors,” said Xiao Zhen Zhou, MD, also of Beth Israel Deaconess Medical Center.

“We therefore used these as a probe in a competition binding assay and screened approximately 8200 chemical compounds, including both approved drugs and other known bioactive compounds.”

To increase screening success, the investigators chose a probe that specifically binds to the Pin1 enzyme active site very tightly, an approach that is not commonly used for this kind of screen.

“Initially, it appeared that the screening results had no positive hits, so we had to manually sift through them looking for the one that would bind to Pin1,” Dr Zhou said. “We eventually spotted cis retinoic acid, which has the same chemical formula as all-trans retinoic acid but with a different chemical structure.”

It turned out that Pin1 prefers binding to ATRA, and cis retinoic acid needs to convert to ATRA in order to bind Pin1.

ATRA in APL and other cancers

ATRA was first discovered for the treatment of APL in 1987. It was originally thought that ATRA was treating APL by inducing cell differentiation, causing cancer cells to change into normal cells by activating the cellular retinoic acid receptors.

But these new findings suggest that is not the mechanism that is actually behind ATRA’s successful outcomes in treating APL.

“While it has been previously shown that ATRA’s ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL, the underlying mechanism has remained elusive,” Dr Lu said.

“Our new, high-throughput drug screening has revealed the ATRA drug target, unexpectedly showing that ATRA directly binds, inhibits, and ultimately degrades active Pin1 selectively in cancer cells. The Pin1-ATRA complex structure suggests that ATRA is trapped in the Pin1 active site by mimicking an unreleasable enzyme substrate. Importantly, ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RAR and treats APL in cell and animal models as well as in human patients.”

The investigators discovered that ATRA-induced Pin1 ablation inhibits triple-negative breast cancer growth as well. The drug proved active in human cells and in animal models, simultaneously turning off many oncogenes and turning on many tumor suppressors.

The team said these results provide a rationale for trying to extend ATRA’s half-life and for developing more potent, Pin1-targeted ATRA variants for cancer treatment.

“The current ATRA drug has a very short half-life of only 45 minutes in humans,” Dr Lu said. “We think that a more potent Pin1 inhibitor will be able to target many ‘dream targets’ that are not currently druggable.”

“ATRA appears to be well tolerated, with minimal side effects, and offers a promising new approach for targeting a Pin1-dependent, common oncogenic mechanism in numerous cancer-driving pathways in cancer and cancer stem cells. This is especially critical for treating aggressive or drug-resistant cancers.”

Micrograph showing APL

Image courtesy of AFIP

New research suggests the vitamin A derivative all-trans retinoic acid (ATRA) inhibits multiple oncogenic pathways and, at the same time, eliminates cancer stem cells by degrading the Pin1 enzyme.

Investigators said this discovery explains how ATRA successfully treats acute promyelocytic leukemia (APL), and it likely has implications for the treatment of other aggressive or drug-resistant cancers.

The team detailed their discovery in Nature Medicine.

“Pin1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease,” said study author Kun Ping Lu, MD, PhD, of Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, Massachusetts.

“Pin1 is a common, key regulator in many types of cancer and, as a result, can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells.”

Until now, agents that inhibit Pin1 have been developed mainly through rational drug design. These inhibitors have proven active against Pin1 in the test tube, but, when tested in a cell model or in vivo, they are unable to efficiently enter cells to successfully inhibit Pin1 function.

In this new work, the investigators decided to take a different approach to identify Pin1 inhibitors. They developed a mechanism-based, high-throughput screen to identify compounds that were targeting active Pin1.

“We had previously identified Pin1 substrate-mimicking peptide inhibitors,” said Xiao Zhen Zhou, MD, also of Beth Israel Deaconess Medical Center.

“We therefore used these as a probe in a competition binding assay and screened approximately 8200 chemical compounds, including both approved drugs and other known bioactive compounds.”

To increase screening success, the investigators chose a probe that specifically binds to the Pin1 enzyme active site very tightly, an approach that is not commonly used for this kind of screen.

“Initially, it appeared that the screening results had no positive hits, so we had to manually sift through them looking for the one that would bind to Pin1,” Dr Zhou said. “We eventually spotted cis retinoic acid, which has the same chemical formula as all-trans retinoic acid but with a different chemical structure.”

It turned out that Pin1 prefers binding to ATRA, and cis retinoic acid needs to convert to ATRA in order to bind Pin1.

ATRA in APL and other cancers

ATRA was first discovered for the treatment of APL in 1987. It was originally thought that ATRA was treating APL by inducing cell differentiation, causing cancer cells to change into normal cells by activating the cellular retinoic acid receptors.

But these new findings suggest that is not the mechanism that is actually behind ATRA’s successful outcomes in treating APL.

“While it has been previously shown that ATRA’s ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL, the underlying mechanism has remained elusive,” Dr Lu said.

“Our new, high-throughput drug screening has revealed the ATRA drug target, unexpectedly showing that ATRA directly binds, inhibits, and ultimately degrades active Pin1 selectively in cancer cells. The Pin1-ATRA complex structure suggests that ATRA is trapped in the Pin1 active site by mimicking an unreleasable enzyme substrate. Importantly, ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RAR and treats APL in cell and animal models as well as in human patients.”

The investigators discovered that ATRA-induced Pin1 ablation inhibits triple-negative breast cancer growth as well. The drug proved active in human cells and in animal models, simultaneously turning off many oncogenes and turning on many tumor suppressors.

The team said these results provide a rationale for trying to extend ATRA’s half-life and for developing more potent, Pin1-targeted ATRA variants for cancer treatment.

“The current ATRA drug has a very short half-life of only 45 minutes in humans,” Dr Lu said. “We think that a more potent Pin1 inhibitor will be able to target many ‘dream targets’ that are not currently druggable.”

“ATRA appears to be well tolerated, with minimal side effects, and offers a promising new approach for targeting a Pin1-dependent, common oncogenic mechanism in numerous cancer-driving pathways in cancer and cancer stem cells. This is especially critical for treating aggressive or drug-resistant cancers.”

Doctor and patient

Photo courtesy of NIH

A new study suggests data breaches of protected health information are on the rise in the US.

Researchers found that, between 2010 and 2013, there were data breaches affecting approximately 29 million records of health information covered

under the Health Insurance Portability and Accountability Act (HIPAA).

Breaches were reported in every state, tended to occur via electronic media, and largely resulted from overt criminal activity.

Vincent Liu, MD, of the Kaiser Permanente Division of Research in Oakland, California, and his colleagues published these findings in JAMA.

The researchers evaluated an online database maintained by the US Department of Health and Human Services that describes data breaches of unencrypted, protected health information (ie, individually identifiable information) reported by entities (health plans and clinicians) covered under HIPAA.

The team included breaches affecting 500 individuals or more that were reported as occurring from 2010 through 2013, accounting for 82% of all reports.

The research revealed 949 breaches affecting 29.1 million records. Six breaches involved more than 1 million records each.

The number of reported breaches increased over time, from 214 in 2010 to 265 in 2013.

Breaches were reported in every state, the District of Columbia, and Puerto Rico. Five states (California, Texas, Florida, New York, and Illinois) accounted for 34% of all breaches. However, when adjusted by population estimates, the states with the highest adjusted number of breaches and affected records varied.

Most breaches occurred via electronic media (67%), frequently involving laptop computers or portable electronic devices (33%). Most breaches also occurred via theft (58%).

The combined frequency of breaches resulting from hacking and unauthorized access or disclosure increased during the study period, from 12% in 2010 to 27% in 2013. Breaches involved external vendors in 29% of reports.

The researchers noted that this study was limited to breaches that were already recognized, reported, and affected at least 500 individuals. Therefore, the team likely underestimated the true number of healthcare data breaches occurring in the US each year.

Doctor and patient

Photo courtesy of NIH

A new study suggests data breaches of protected health information are on the rise in the US.

Researchers found that, between 2010 and 2013, there were data breaches affecting approximately 29 million records of health information covered

under the Health Insurance Portability and Accountability Act (HIPAA).

Breaches were reported in every state, tended to occur via electronic media, and largely resulted from overt criminal activity.

Vincent Liu, MD, of the Kaiser Permanente Division of Research in Oakland, California, and his colleagues published these findings in JAMA.

The researchers evaluated an online database maintained by the US Department of Health and Human Services that describes data breaches of unencrypted, protected health information (ie, individually identifiable information) reported by entities (health plans and clinicians) covered under HIPAA.

The team included breaches affecting 500 individuals or more that were reported as occurring from 2010 through 2013, accounting for 82% of all reports.

The research revealed 949 breaches affecting 29.1 million records. Six breaches involved more than 1 million records each.

The number of reported breaches increased over time, from 214 in 2010 to 265 in 2013.

Breaches were reported in every state, the District of Columbia, and Puerto Rico. Five states (California, Texas, Florida, New York, and Illinois) accounted for 34% of all breaches. However, when adjusted by population estimates, the states with the highest adjusted number of breaches and affected records varied.

Most breaches occurred via electronic media (67%), frequently involving laptop computers or portable electronic devices (33%). Most breaches also occurred via theft (58%).

The combined frequency of breaches resulting from hacking and unauthorized access or disclosure increased during the study period, from 12% in 2010 to 27% in 2013. Breaches involved external vendors in 29% of reports.

The researchers noted that this study was limited to breaches that were already recognized, reported, and affected at least 500 individuals. Therefore, the team likely underestimated the true number of healthcare data breaches occurring in the US each year.

Doctor and patient

Photo courtesy of NIH

A new study suggests data breaches of protected health information are on the rise in the US.

Researchers found that, between 2010 and 2013, there were data breaches affecting approximately 29 million records of health information covered

under the Health Insurance Portability and Accountability Act (HIPAA).

Breaches were reported in every state, tended to occur via electronic media, and largely resulted from overt criminal activity.

Vincent Liu, MD, of the Kaiser Permanente Division of Research in Oakland, California, and his colleagues published these findings in JAMA.

The researchers evaluated an online database maintained by the US Department of Health and Human Services that describes data breaches of unencrypted, protected health information (ie, individually identifiable information) reported by entities (health plans and clinicians) covered under HIPAA.

The team included breaches affecting 500 individuals or more that were reported as occurring from 2010 through 2013, accounting for 82% of all reports.

The research revealed 949 breaches affecting 29.1 million records. Six breaches involved more than 1 million records each.

The number of reported breaches increased over time, from 214 in 2010 to 265 in 2013.

Breaches were reported in every state, the District of Columbia, and Puerto Rico. Five states (California, Texas, Florida, New York, and Illinois) accounted for 34% of all breaches. However, when adjusted by population estimates, the states with the highest adjusted number of breaches and affected records varied.

Most breaches occurred via electronic media (67%), frequently involving laptop computers or portable electronic devices (33%). Most breaches also occurred via theft (58%).

The combined frequency of breaches resulting from hacking and unauthorized access or disclosure increased during the study period, from 12% in 2010 to 27% in 2013. Breaches involved external vendors in 29% of reports.

The researchers noted that this study was limited to breaches that were already recognized, reported, and affected at least 500 individuals. Therefore, the team likely underestimated the true number of healthcare data breaches occurring in the US each year.

Doctor using a smartphone

Photo by Daniel Sone

Scientists say a smartphone-based system could bring rapid, accurate molecular diagnosis of cancers and other diseases to locations lacking the latest medical technology.

In PNAS, the group explained how the digital diffraction diagnosis (D3) system collects detailed microscopic images for digital analysis of the molecular composition of cells and tissues.

In pilot experiments, the system enabled accurate diagnoses of lymphoma and cervical cancer.

“The emerging genomic and biological data for various cancers, which can be essential to choosing the most appropriate therapy, supports the need for molecular profiling strategies that are more accessible to providers, clinical investigators, and patients,” said study author Cesar Castro, MD, of Massachusetts General Hospital in Boston.

“And we believe the platform we have developed provides essential features at an extraordinarily low cost.”

The D3 system features an imaging module with a battery-powered LED light clipped onto a standard smartphone that records high-resolution imaging data with its camera.

With a greater field of view than traditional microscopy, the D3 system is capable of recording data on more than 100,000 cells from a blood or tissue sample in a single image. The data can then be transmitted for analysis to a remote graphic-processing server via a secure, encrypted cloud service, and the results returned to the point of care.

For molecular analysis of tumors, a sample of blood or tissue is labeled with microbeads that bind to known cancer-related molecules and loaded into the D3 imaging module.

After the image is recorded and data transmitted to the server, the presence of specific molecules is detected by analyzing the diffraction patterns generated by the microbeads. The use of variously sized or coated beads may offer unique diffraction signatures to facilitate detection.

A numerical algorithm the researchers developed can distinguish cells from beads and analyze as much as 10 MB of data in less than nine hundredths of a second.

In a pilot test with cancer cell lines, the D3 system detected the presence of tumor proteins with an accuracy matching that of the current gold standard for molecular profiling. And the system’s larger field of view enabled simultaneous analysis of more than 100,000 cells at a time.

The researchers also conducted analyses of cervical biopsy samples from 25 women with abnormal PAP smears—samples collected along with those used for clinical diagnosis—using microbeads tagged with antibodies against 3 published markers of cervical cancer.

Based on the number of antibody-tagged microbeads binding to cells, D3 analysis promptly and reliably categorized biopsy samples as high-risk, low-risk, or benign. Results matched those of conventional pathologic analysis.

In addition, D3 analysis of fine-needle lymph node biopsy samples was accurately able to differentiate 4 patients whose lymphoma diagnosis was confirmed by conventional pathology from another 4 patients with benign lymph node enlargement.

Along with protein analyses, the D3 system was enhanced to successfully detect DNA—in this instance, from human papilloma virus—with great sensitivity.

In all of these tests, results were available in under an hour and at a cost of $1.80 per assay, a price that would be expected to drop with further refinement of the D3 system.

“We expect that the D3 platform will enhance the breadth and depth of cancer screening in a way that is feasible and sustainable for resource limited-settings,” said Ralph Weissleder, MD, PhD, also of Massachusetts General Hospital.

“By taking advantage of the increased penetration of mobile phone technology worldwide, the system should allow the prompt triaging of suspicious or high-risk cases that could help to offset delays caused by limited pathology services in those regions and reduce the need for patients to return for follow-up care, which is often challenging for them.”

The researchers’ next steps are to investigate D3’s ability to analyze protein and DNA markers of other disease catalysts, integrate the software with larger databases, and conduct clinical studies in settings such as care-delivery sites in developing countries or rural areas.

Massachusetts General Hospital has filed a patent application covering the D3 technology.

Doctor using a smartphone

Photo by Daniel Sone

Scientists say a smartphone-based system could bring rapid, accurate molecular diagnosis of cancers and other diseases to locations lacking the latest medical technology.

In PNAS, the group explained how the digital diffraction diagnosis (D3) system collects detailed microscopic images for digital analysis of the molecular composition of cells and tissues.

In pilot experiments, the system enabled accurate diagnoses of lymphoma and cervical cancer.

“The emerging genomic and biological data for various cancers, which can be essential to choosing the most appropriate therapy, supports the need for molecular profiling strategies that are more accessible to providers, clinical investigators, and patients,” said study author Cesar Castro, MD, of Massachusetts General Hospital in Boston.

“And we believe the platform we have developed provides essential features at an extraordinarily low cost.”

The D3 system features an imaging module with a battery-powered LED light clipped onto a standard smartphone that records high-resolution imaging data with its camera.

With a greater field of view than traditional microscopy, the D3 system is capable of recording data on more than 100,000 cells from a blood or tissue sample in a single image. The data can then be transmitted for analysis to a remote graphic-processing server via a secure, encrypted cloud service, and the results returned to the point of care.

For molecular analysis of tumors, a sample of blood or tissue is labeled with microbeads that bind to known cancer-related molecules and loaded into the D3 imaging module.

After the image is recorded and data transmitted to the server, the presence of specific molecules is detected by analyzing the diffraction patterns generated by the microbeads. The use of variously sized or coated beads may offer unique diffraction signatures to facilitate detection.

A numerical algorithm the researchers developed can distinguish cells from beads and analyze as much as 10 MB of data in less than nine hundredths of a second.

In a pilot test with cancer cell lines, the D3 system detected the presence of tumor proteins with an accuracy matching that of the current gold standard for molecular profiling. And the system’s larger field of view enabled simultaneous analysis of more than 100,000 cells at a time.

The researchers also conducted analyses of cervical biopsy samples from 25 women with abnormal PAP smears—samples collected along with those used for clinical diagnosis—using microbeads tagged with antibodies against 3 published markers of cervical cancer.

Based on the number of antibody-tagged microbeads binding to cells, D3 analysis promptly and reliably categorized biopsy samples as high-risk, low-risk, or benign. Results matched those of conventional pathologic analysis.

In addition, D3 analysis of fine-needle lymph node biopsy samples was accurately able to differentiate 4 patients whose lymphoma diagnosis was confirmed by conventional pathology from another 4 patients with benign lymph node enlargement.

Along with protein analyses, the D3 system was enhanced to successfully detect DNA—in this instance, from human papilloma virus—with great sensitivity.

In all of these tests, results were available in under an hour and at a cost of $1.80 per assay, a price that would be expected to drop with further refinement of the D3 system.

“We expect that the D3 platform will enhance the breadth and depth of cancer screening in a way that is feasible and sustainable for resource limited-settings,” said Ralph Weissleder, MD, PhD, also of Massachusetts General Hospital.

“By taking advantage of the increased penetration of mobile phone technology worldwide, the system should allow the prompt triaging of suspicious or high-risk cases that could help to offset delays caused by limited pathology services in those regions and reduce the need for patients to return for follow-up care, which is often challenging for them.”

The researchers’ next steps are to investigate D3’s ability to analyze protein and DNA markers of other disease catalysts, integrate the software with larger databases, and conduct clinical studies in settings such as care-delivery sites in developing countries or rural areas.

Massachusetts General Hospital has filed a patent application covering the D3 technology.

Doctor using a smartphone

Photo by Daniel Sone

Scientists say a smartphone-based system could bring rapid, accurate molecular diagnosis of cancers and other diseases to locations lacking the latest medical technology.

In PNAS, the group explained how the digital diffraction diagnosis (D3) system collects detailed microscopic images for digital analysis of the molecular composition of cells and tissues.

In pilot experiments, the system enabled accurate diagnoses of lymphoma and cervical cancer.

“The emerging genomic and biological data for various cancers, which can be essential to choosing the most appropriate therapy, supports the need for molecular profiling strategies that are more accessible to providers, clinical investigators, and patients,” said study author Cesar Castro, MD, of Massachusetts General Hospital in Boston.

“And we believe the platform we have developed provides essential features at an extraordinarily low cost.”

The D3 system features an imaging module with a battery-powered LED light clipped onto a standard smartphone that records high-resolution imaging data with its camera.

With a greater field of view than traditional microscopy, the D3 system is capable of recording data on more than 100,000 cells from a blood or tissue sample in a single image. The data can then be transmitted for analysis to a remote graphic-processing server via a secure, encrypted cloud service, and the results returned to the point of care.

For molecular analysis of tumors, a sample of blood or tissue is labeled with microbeads that bind to known cancer-related molecules and loaded into the D3 imaging module.

After the image is recorded and data transmitted to the server, the presence of specific molecules is detected by analyzing the diffraction patterns generated by the microbeads. The use of variously sized or coated beads may offer unique diffraction signatures to facilitate detection.

A numerical algorithm the researchers developed can distinguish cells from beads and analyze as much as 10 MB of data in less than nine hundredths of a second.

In a pilot test with cancer cell lines, the D3 system detected the presence of tumor proteins with an accuracy matching that of the current gold standard for molecular profiling. And the system’s larger field of view enabled simultaneous analysis of more than 100,000 cells at a time.

The researchers also conducted analyses of cervical biopsy samples from 25 women with abnormal PAP smears—samples collected along with those used for clinical diagnosis—using microbeads tagged with antibodies against 3 published markers of cervical cancer.

Based on the number of antibody-tagged microbeads binding to cells, D3 analysis promptly and reliably categorized biopsy samples as high-risk, low-risk, or benign. Results matched those of conventional pathologic analysis.

In addition, D3 analysis of fine-needle lymph node biopsy samples was accurately able to differentiate 4 patients whose lymphoma diagnosis was confirmed by conventional pathology from another 4 patients with benign lymph node enlargement.

Along with protein analyses, the D3 system was enhanced to successfully detect DNA—in this instance, from human papilloma virus—with great sensitivity.

In all of these tests, results were available in under an hour and at a cost of $1.80 per assay, a price that would be expected to drop with further refinement of the D3 system.

“We expect that the D3 platform will enhance the breadth and depth of cancer screening in a way that is feasible and sustainable for resource limited-settings,” said Ralph Weissleder, MD, PhD, also of Massachusetts General Hospital.

“By taking advantage of the increased penetration of mobile phone technology worldwide, the system should allow the prompt triaging of suspicious or high-risk cases that could help to offset delays caused by limited pathology services in those regions and reduce the need for patients to return for follow-up care, which is often challenging for them.”

The researchers’ next steps are to investigate D3’s ability to analyze protein and DNA markers of other disease catalysts, integrate the software with larger databases, and conduct clinical studies in settings such as care-delivery sites in developing countries or rural areas.

Massachusetts General Hospital has filed a patent application covering the D3 technology.