PARIS – The leaders of European interventional cardiology have thrown down the gauntlet to their colleagues, declaring during a special call-to-action session at EuroPCR that a revolution is underway in the treatment of acute stroke, and interventional cardiologists need to train up and become part of it.

“Something big is going on today. If we want to be transformative and impactful, I think stroke intervention is one of the main points where we can do so as interventional cardiologists,” said Dr. Alberto Cremonesi of Villa Maria Cecilia Hospital in Cotignola, Italy, a past president of the Italian Society of Interventional Cardiology.

Bruce Jancin/Frontline Medical News

Dr. Petr Widimsky highlighted the five prospective, randomized, controlled trials that have come out in the past few months and triggered the revolution in acute stroke therapy. All five studies – MR CLEAN, ESCAPE, EXTENT IA, SWIFT PRIME, and REVASCAT – were halted early because of the significant advantage mechanical endovascular therapy with stents or thrombus retrieval devices demonstrated over standard therapy featuring clot thrombolysis with tissue plasminogen activator.

Collectively, the five trials showed a 60% greater chance for good functional recovery from stroke with endovascular interventions. The rate of a favorable neurologic outcome as reflected in a modified Rankin score of 0-2 was 48% with the use of stent/retriever devices, compared with 30% with thrombolysis alone, noted Dr. Widimsky, professor and chair of the cardiology department at Charles University in Prague.

The Food and Drug Administration began approving these endovascular therapy devices in 2012. The major challenge is how to make this therapy available to the vast numbers of patients in need. After all, the successful clinical trials were carried out by highly skilled interventional neuroradiologists operating in centers of excellence – yet such centers are few and far between.

“There should be no fight between the specialties. In hospitals with high patient volume and good work flow and experienced neuroradiologists available 24/7, there is no need for cardiologists to jump in. But in hospitals where that’s not the case then cardiologists can be of help,” he asserted at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

There aren’t nearly enough interventional neuroradiologists or endovascularly trained neurosurgeons to fill the enormous need, and neurologists simply don’t have the mindset for this sort of work, Dr. Widimsky added.

“Neurologists, with few exceptions, don’t do interventions. In general, they are people who think conservatively. These procedures should be done by someone who is working with procedures every day, and that’s not what neurologists do,” he continued.

Because interventional neuroradiology services weren’t available at Dr. Widimsky’s hospital, he and his fellow interventional cardiologists took on the task several years ago, gaining specialized training and then forming a multidisciplinary acute stroke team. The results, he said, have been gratifying.

The new endovascular therapy for acute stroke has much in common with contemporary management of ST-elevation MI, Dr. Widimsky observed. Just as in an acute MI, where time is heart muscle, in acute stroke time is brain. In most patients, the endovascular procedures are most effective when done within 3 hours after acute stroke onset. By 6 hours, the rate of good functional recovery falls to about 20%. But some patients can derive benefit even with much later intervention provided they have sufficient collateral circulation, which can be determined by sophisticated perfusion imaging techniques.

Dr. Widimsky pointed out a couple of ways to streamline today’s standard acute stroke management flow in order to save substantial time. The typical pathway today is for EMS personnel to take a patient to the emergency department for evaluation for suspected stroke, which can take up to 30 minutes. That patient then goes to CT imaging to determine whether the stroke is ischemic or hemorrhagic, then to the neurology unit for thrombolytic therapy, which can take another 30-60 minutes. Only afterwards, if indicated, does the patient go to the catheterization laboratory for endovascular intervention.

A faster, better approach, he said, is to train EMS personnel to recognize suspected cases of acute stroke, have them bypass the ED and instead take those patients straight to a hospital with high-quality CT imaging available 24/7, and if imaging indicates the patient is a candidate for mechanical revascularization, to then bypass the thrombolysis suite and go directly to the catheterization laboratory. That can save an hour to an hour-and-a-half in total.

Who should be performing these endovascular interventions? Dr. Alain Bonafe presented highlights of a recent joint consensus statement by the European Stroke Organization, the European Society of Minimally Invasive Neurological Therapy, and the European Society of Neuroradiology that declared the decision to undertake these procedures should be made jointly by a multidisciplinary team in experienced centers providing comprehensive stroke care, and that the procedures should be carried out by accredited interventionalists with certified expertise, regardless of their specialty.

“We must offer this intervention to as many patients as possible,” stressed Dr. Bonafe, professor of neuroradiology at the University of Toulouse and president of the French Society of Neuroradiology. “In most places it’s not offered at all, or only part-time by a few experts. So I think cardiologists should join the force, and everybody who is expert in procedural interventions should be trained for this in order to cover the need for the whole population.”

Dr. Kenneth K. Snyder observed that as recently as 2013, the rumor was that endovascular stroke therapy was dead. Three randomized trials published in the New England Journal of Medicine – IMS III, SYNTHESIS, and MR RESCUE – had found no difference between endovascular therapy and standard medical therapy.

But only 5% of the participants in those trials were treated with modern clot retrievers, which are much more effective than earlier-generation devices. And the negative trials didn’t specifically target large-vessel occlusions, which is where device therapy clearly works best.

“Stroke is now a surgical disease. Many of us have believed this from the get go. In centers with advanced systems of stroke care, endovascular therapy can significantly improve functional outcomes without compromising safety as compared to standard therapy,” said Dr. Snyder, a neurosurgeon specializing in endovascular therapy at the State University of New York at Buffalo.

In the United States, he noted, stroke is the fourth leading cause of mortality, the No. 1 cause of long-term disability, the most common discharge diagnosis to nursing homes, and carries a cost of $70 billion annually. Worldwide, stroke is the second leading cause of mortality. And stroke rates will continue to grow.

He said conflict between specialties regarding provision of state-of-the-art acute stroke therapy is not inevitable, as can be seen at the acute stroke unit at SUNY Buffalo.

“Our center is collaborative and multidisciplinary. We have 20 interventional suites. We all work next to each other and with each other – the cardiologists next to the interventional radiologists next to the neurosurgeons. It forces a great deal of collaboration. And we have a track record of training cardiologists both in observerships and also in formal training programs,” Dr. Snyder said.

The speakers declared having no financial conflicts.

[email protected]

PARIS – The leaders of European interventional cardiology have thrown down the gauntlet to their colleagues, declaring during a special call-to-action session at EuroPCR that a revolution is underway in the treatment of acute stroke, and interventional cardiologists need to train up and become part of it.

“Something big is going on today. If we want to be transformative and impactful, I think stroke intervention is one of the main points where we can do so as interventional cardiologists,” said Dr. Alberto Cremonesi of Villa Maria Cecilia Hospital in Cotignola, Italy, a past president of the Italian Society of Interventional Cardiology.

Bruce Jancin/Frontline Medical News

Dr. Petr Widimsky highlighted the five prospective, randomized, controlled trials that have come out in the past few months and triggered the revolution in acute stroke therapy. All five studies – MR CLEAN, ESCAPE, EXTENT IA, SWIFT PRIME, and REVASCAT – were halted early because of the significant advantage mechanical endovascular therapy with stents or thrombus retrieval devices demonstrated over standard therapy featuring clot thrombolysis with tissue plasminogen activator.

Collectively, the five trials showed a 60% greater chance for good functional recovery from stroke with endovascular interventions. The rate of a favorable neurologic outcome as reflected in a modified Rankin score of 0-2 was 48% with the use of stent/retriever devices, compared with 30% with thrombolysis alone, noted Dr. Widimsky, professor and chair of the cardiology department at Charles University in Prague.

The Food and Drug Administration began approving these endovascular therapy devices in 2012. The major challenge is how to make this therapy available to the vast numbers of patients in need. After all, the successful clinical trials were carried out by highly skilled interventional neuroradiologists operating in centers of excellence – yet such centers are few and far between.

“There should be no fight between the specialties. In hospitals with high patient volume and good work flow and experienced neuroradiologists available 24/7, there is no need for cardiologists to jump in. But in hospitals where that’s not the case then cardiologists can be of help,” he asserted at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

There aren’t nearly enough interventional neuroradiologists or endovascularly trained neurosurgeons to fill the enormous need, and neurologists simply don’t have the mindset for this sort of work, Dr. Widimsky added.

“Neurologists, with few exceptions, don’t do interventions. In general, they are people who think conservatively. These procedures should be done by someone who is working with procedures every day, and that’s not what neurologists do,” he continued.

Because interventional neuroradiology services weren’t available at Dr. Widimsky’s hospital, he and his fellow interventional cardiologists took on the task several years ago, gaining specialized training and then forming a multidisciplinary acute stroke team. The results, he said, have been gratifying.

The new endovascular therapy for acute stroke has much in common with contemporary management of ST-elevation MI, Dr. Widimsky observed. Just as in an acute MI, where time is heart muscle, in acute stroke time is brain. In most patients, the endovascular procedures are most effective when done within 3 hours after acute stroke onset. By 6 hours, the rate of good functional recovery falls to about 20%. But some patients can derive benefit even with much later intervention provided they have sufficient collateral circulation, which can be determined by sophisticated perfusion imaging techniques.

Dr. Widimsky pointed out a couple of ways to streamline today’s standard acute stroke management flow in order to save substantial time. The typical pathway today is for EMS personnel to take a patient to the emergency department for evaluation for suspected stroke, which can take up to 30 minutes. That patient then goes to CT imaging to determine whether the stroke is ischemic or hemorrhagic, then to the neurology unit for thrombolytic therapy, which can take another 30-60 minutes. Only afterwards, if indicated, does the patient go to the catheterization laboratory for endovascular intervention.

A faster, better approach, he said, is to train EMS personnel to recognize suspected cases of acute stroke, have them bypass the ED and instead take those patients straight to a hospital with high-quality CT imaging available 24/7, and if imaging indicates the patient is a candidate for mechanical revascularization, to then bypass the thrombolysis suite and go directly to the catheterization laboratory. That can save an hour to an hour-and-a-half in total.

Who should be performing these endovascular interventions? Dr. Alain Bonafe presented highlights of a recent joint consensus statement by the European Stroke Organization, the European Society of Minimally Invasive Neurological Therapy, and the European Society of Neuroradiology that declared the decision to undertake these procedures should be made jointly by a multidisciplinary team in experienced centers providing comprehensive stroke care, and that the procedures should be carried out by accredited interventionalists with certified expertise, regardless of their specialty.

“We must offer this intervention to as many patients as possible,” stressed Dr. Bonafe, professor of neuroradiology at the University of Toulouse and president of the French Society of Neuroradiology. “In most places it’s not offered at all, or only part-time by a few experts. So I think cardiologists should join the force, and everybody who is expert in procedural interventions should be trained for this in order to cover the need for the whole population.”

Dr. Kenneth K. Snyder observed that as recently as 2013, the rumor was that endovascular stroke therapy was dead. Three randomized trials published in the New England Journal of Medicine – IMS III, SYNTHESIS, and MR RESCUE – had found no difference between endovascular therapy and standard medical therapy.

But only 5% of the participants in those trials were treated with modern clot retrievers, which are much more effective than earlier-generation devices. And the negative trials didn’t specifically target large-vessel occlusions, which is where device therapy clearly works best.

“Stroke is now a surgical disease. Many of us have believed this from the get go. In centers with advanced systems of stroke care, endovascular therapy can significantly improve functional outcomes without compromising safety as compared to standard therapy,” said Dr. Snyder, a neurosurgeon specializing in endovascular therapy at the State University of New York at Buffalo.

In the United States, he noted, stroke is the fourth leading cause of mortality, the No. 1 cause of long-term disability, the most common discharge diagnosis to nursing homes, and carries a cost of $70 billion annually. Worldwide, stroke is the second leading cause of mortality. And stroke rates will continue to grow.

He said conflict between specialties regarding provision of state-of-the-art acute stroke therapy is not inevitable, as can be seen at the acute stroke unit at SUNY Buffalo.

“Our center is collaborative and multidisciplinary. We have 20 interventional suites. We all work next to each other and with each other – the cardiologists next to the interventional radiologists next to the neurosurgeons. It forces a great deal of collaboration. And we have a track record of training cardiologists both in observerships and also in formal training programs,” Dr. Snyder said.

The speakers declared having no financial conflicts.

[email protected]

PARIS – The leaders of European interventional cardiology have thrown down the gauntlet to their colleagues, declaring during a special call-to-action session at EuroPCR that a revolution is underway in the treatment of acute stroke, and interventional cardiologists need to train up and become part of it.

“Something big is going on today. If we want to be transformative and impactful, I think stroke intervention is one of the main points where we can do so as interventional cardiologists,” said Dr. Alberto Cremonesi of Villa Maria Cecilia Hospital in Cotignola, Italy, a past president of the Italian Society of Interventional Cardiology.

Bruce Jancin/Frontline Medical News

Dr. Petr Widimsky highlighted the five prospective, randomized, controlled trials that have come out in the past few months and triggered the revolution in acute stroke therapy. All five studies – MR CLEAN, ESCAPE, EXTENT IA, SWIFT PRIME, and REVASCAT – were halted early because of the significant advantage mechanical endovascular therapy with stents or thrombus retrieval devices demonstrated over standard therapy featuring clot thrombolysis with tissue plasminogen activator.

Collectively, the five trials showed a 60% greater chance for good functional recovery from stroke with endovascular interventions. The rate of a favorable neurologic outcome as reflected in a modified Rankin score of 0-2 was 48% with the use of stent/retriever devices, compared with 30% with thrombolysis alone, noted Dr. Widimsky, professor and chair of the cardiology department at Charles University in Prague.

The Food and Drug Administration began approving these endovascular therapy devices in 2012. The major challenge is how to make this therapy available to the vast numbers of patients in need. After all, the successful clinical trials were carried out by highly skilled interventional neuroradiologists operating in centers of excellence – yet such centers are few and far between.

“There should be no fight between the specialties. In hospitals with high patient volume and good work flow and experienced neuroradiologists available 24/7, there is no need for cardiologists to jump in. But in hospitals where that’s not the case then cardiologists can be of help,” he asserted at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

There aren’t nearly enough interventional neuroradiologists or endovascularly trained neurosurgeons to fill the enormous need, and neurologists simply don’t have the mindset for this sort of work, Dr. Widimsky added.

“Neurologists, with few exceptions, don’t do interventions. In general, they are people who think conservatively. These procedures should be done by someone who is working with procedures every day, and that’s not what neurologists do,” he continued.

Because interventional neuroradiology services weren’t available at Dr. Widimsky’s hospital, he and his fellow interventional cardiologists took on the task several years ago, gaining specialized training and then forming a multidisciplinary acute stroke team. The results, he said, have been gratifying.

The new endovascular therapy for acute stroke has much in common with contemporary management of ST-elevation MI, Dr. Widimsky observed. Just as in an acute MI, where time is heart muscle, in acute stroke time is brain. In most patients, the endovascular procedures are most effective when done within 3 hours after acute stroke onset. By 6 hours, the rate of good functional recovery falls to about 20%. But some patients can derive benefit even with much later intervention provided they have sufficient collateral circulation, which can be determined by sophisticated perfusion imaging techniques.

Dr. Widimsky pointed out a couple of ways to streamline today’s standard acute stroke management flow in order to save substantial time. The typical pathway today is for EMS personnel to take a patient to the emergency department for evaluation for suspected stroke, which can take up to 30 minutes. That patient then goes to CT imaging to determine whether the stroke is ischemic or hemorrhagic, then to the neurology unit for thrombolytic therapy, which can take another 30-60 minutes. Only afterwards, if indicated, does the patient go to the catheterization laboratory for endovascular intervention.

A faster, better approach, he said, is to train EMS personnel to recognize suspected cases of acute stroke, have them bypass the ED and instead take those patients straight to a hospital with high-quality CT imaging available 24/7, and if imaging indicates the patient is a candidate for mechanical revascularization, to then bypass the thrombolysis suite and go directly to the catheterization laboratory. That can save an hour to an hour-and-a-half in total.

Who should be performing these endovascular interventions? Dr. Alain Bonafe presented highlights of a recent joint consensus statement by the European Stroke Organization, the European Society of Minimally Invasive Neurological Therapy, and the European Society of Neuroradiology that declared the decision to undertake these procedures should be made jointly by a multidisciplinary team in experienced centers providing comprehensive stroke care, and that the procedures should be carried out by accredited interventionalists with certified expertise, regardless of their specialty.

“We must offer this intervention to as many patients as possible,” stressed Dr. Bonafe, professor of neuroradiology at the University of Toulouse and president of the French Society of Neuroradiology. “In most places it’s not offered at all, or only part-time by a few experts. So I think cardiologists should join the force, and everybody who is expert in procedural interventions should be trained for this in order to cover the need for the whole population.”

Dr. Kenneth K. Snyder observed that as recently as 2013, the rumor was that endovascular stroke therapy was dead. Three randomized trials published in the New England Journal of Medicine – IMS III, SYNTHESIS, and MR RESCUE – had found no difference between endovascular therapy and standard medical therapy.

But only 5% of the participants in those trials were treated with modern clot retrievers, which are much more effective than earlier-generation devices. And the negative trials didn’t specifically target large-vessel occlusions, which is where device therapy clearly works best.

“Stroke is now a surgical disease. Many of us have believed this from the get go. In centers with advanced systems of stroke care, endovascular therapy can significantly improve functional outcomes without compromising safety as compared to standard therapy,” said Dr. Snyder, a neurosurgeon specializing in endovascular therapy at the State University of New York at Buffalo.

In the United States, he noted, stroke is the fourth leading cause of mortality, the No. 1 cause of long-term disability, the most common discharge diagnosis to nursing homes, and carries a cost of $70 billion annually. Worldwide, stroke is the second leading cause of mortality. And stroke rates will continue to grow.

He said conflict between specialties regarding provision of state-of-the-art acute stroke therapy is not inevitable, as can be seen at the acute stroke unit at SUNY Buffalo.

“Our center is collaborative and multidisciplinary. We have 20 interventional suites. We all work next to each other and with each other – the cardiologists next to the interventional radiologists next to the neurosurgeons. It forces a great deal of collaboration. And we have a track record of training cardiologists both in observerships and also in formal training programs,” Dr. Snyder said.

The speakers declared having no financial conflicts.

[email protected]

The Wells score is only slightly better than a coin toss for predicting deep vein thrombosis (DVT) in hospitalized patients, researchers have found.

"The Wells score risk stratification is not sufficient to rule out DVT or influence management decisions in the inpatient setting," Dr. Patricia C. Silveira from Brigham and Women’s Hospital in Boston says.

Although the Wells score has been validated in outpatient and ED settings, it has not been studied in hospitalized patients in a large prospective trial, Dr. Silveira and her colleagues note in JAMA Internal Medicine, online May 18.

The team evaluated the utility of the tool for risk stratification of inpatients with suspected DVT in a prospective study that included more than 1,100 patients. About one in eight were found on lower-extremity venous duplex ultrasound studies (LEUS) to have proximal DVT and 9.2% to have distal DVT.

The incidence of proximal DVT in the low, moderate, and high Wells pretest probability groups was 5.9%, 9.5%, and 16.4%, respectively, a much narrower range than was previously reported for outpatients (3.0%, 16.6%, and 74.6%).

The AUC for the discriminatory accuracy of the Wells score for risk of proximal DVT identified on LEUS was only 0.6 (a coin toss would yield a predicted AUC of 0.5), the researchers found.

Results were even less informative for distal DVT, where low, moderate, and high pretest probability groups had DVT incidences of 7.4%, 9.1%, and 9.7%, respectively.

"Physician should use their clinical judgment to order lower extremity ultrasound studies for hospitalized patients with suspected DVT," Dr. Silveira concludes. "A new clinical decision rule might be useful to determine a patient's pre-test probability of DVT in the inpatient setting."

Dr. Erika Leemann Price from San Francisco Veterans Affairs Medical Center in California, who coauthored an invited commentary on the new report, told Reuters Health by email, "In the inpatient setting, the Wells score for DVT doesn't do a good job of telling us who has a DVT and who doesn't. Inpatients are different from outpatients in that they are at greater risk for DVT overall, but they also have multiple other comorbidities that can mimic the signs and symptoms of DVT.

"We don't currently have a validated clinical prediction model for DVT in the inpatient setting, although there is clearly a need for one that includes factors more predictive of VTE (venous thromboembolism) specifically in inpatients," Dr. Price says. "For now, if you are worried that your hospitalized patient may have a DVT, skip the Wells score and get an ultrasound." TH

—Reuters Health

The Wells score is only slightly better than a coin toss for predicting deep vein thrombosis (DVT) in hospitalized patients, researchers have found.

"The Wells score risk stratification is not sufficient to rule out DVT or influence management decisions in the inpatient setting," Dr. Patricia C. Silveira from Brigham and Women’s Hospital in Boston says.

Although the Wells score has been validated in outpatient and ED settings, it has not been studied in hospitalized patients in a large prospective trial, Dr. Silveira and her colleagues note in JAMA Internal Medicine, online May 18.

The team evaluated the utility of the tool for risk stratification of inpatients with suspected DVT in a prospective study that included more than 1,100 patients. About one in eight were found on lower-extremity venous duplex ultrasound studies (LEUS) to have proximal DVT and 9.2% to have distal DVT.

The incidence of proximal DVT in the low, moderate, and high Wells pretest probability groups was 5.9%, 9.5%, and 16.4%, respectively, a much narrower range than was previously reported for outpatients (3.0%, 16.6%, and 74.6%).

The AUC for the discriminatory accuracy of the Wells score for risk of proximal DVT identified on LEUS was only 0.6 (a coin toss would yield a predicted AUC of 0.5), the researchers found.

Results were even less informative for distal DVT, where low, moderate, and high pretest probability groups had DVT incidences of 7.4%, 9.1%, and 9.7%, respectively.

"Physician should use their clinical judgment to order lower extremity ultrasound studies for hospitalized patients with suspected DVT," Dr. Silveira concludes. "A new clinical decision rule might be useful to determine a patient's pre-test probability of DVT in the inpatient setting."

Dr. Erika Leemann Price from San Francisco Veterans Affairs Medical Center in California, who coauthored an invited commentary on the new report, told Reuters Health by email, "In the inpatient setting, the Wells score for DVT doesn't do a good job of telling us who has a DVT and who doesn't. Inpatients are different from outpatients in that they are at greater risk for DVT overall, but they also have multiple other comorbidities that can mimic the signs and symptoms of DVT.

"We don't currently have a validated clinical prediction model for DVT in the inpatient setting, although there is clearly a need for one that includes factors more predictive of VTE (venous thromboembolism) specifically in inpatients," Dr. Price says. "For now, if you are worried that your hospitalized patient may have a DVT, skip the Wells score and get an ultrasound." TH

—Reuters Health

The Wells score is only slightly better than a coin toss for predicting deep vein thrombosis (DVT) in hospitalized patients, researchers have found.

"The Wells score risk stratification is not sufficient to rule out DVT or influence management decisions in the inpatient setting," Dr. Patricia C. Silveira from Brigham and Women’s Hospital in Boston says.

Although the Wells score has been validated in outpatient and ED settings, it has not been studied in hospitalized patients in a large prospective trial, Dr. Silveira and her colleagues note in JAMA Internal Medicine, online May 18.

The team evaluated the utility of the tool for risk stratification of inpatients with suspected DVT in a prospective study that included more than 1,100 patients. About one in eight were found on lower-extremity venous duplex ultrasound studies (LEUS) to have proximal DVT and 9.2% to have distal DVT.

The incidence of proximal DVT in the low, moderate, and high Wells pretest probability groups was 5.9%, 9.5%, and 16.4%, respectively, a much narrower range than was previously reported for outpatients (3.0%, 16.6%, and 74.6%).

The AUC for the discriminatory accuracy of the Wells score for risk of proximal DVT identified on LEUS was only 0.6 (a coin toss would yield a predicted AUC of 0.5), the researchers found.

Results were even less informative for distal DVT, where low, moderate, and high pretest probability groups had DVT incidences of 7.4%, 9.1%, and 9.7%, respectively.

"Physician should use their clinical judgment to order lower extremity ultrasound studies for hospitalized patients with suspected DVT," Dr. Silveira concludes. "A new clinical decision rule might be useful to determine a patient's pre-test probability of DVT in the inpatient setting."

Dr. Erika Leemann Price from San Francisco Veterans Affairs Medical Center in California, who coauthored an invited commentary on the new report, told Reuters Health by email, "In the inpatient setting, the Wells score for DVT doesn't do a good job of telling us who has a DVT and who doesn't. Inpatients are different from outpatients in that they are at greater risk for DVT overall, but they also have multiple other comorbidities that can mimic the signs and symptoms of DVT.

"We don't currently have a validated clinical prediction model for DVT in the inpatient setting, although there is clearly a need for one that includes factors more predictive of VTE (venous thromboembolism) specifically in inpatients," Dr. Price says. "For now, if you are worried that your hospitalized patient may have a DVT, skip the Wells score and get an ultrasound." TH

—Reuters Health

Paul Spagnuolo, PhD, in the

lab, surrounded by avocados

Photo by Light Imaging/

University of Waterloo

A compound derived from avocados could be effective in treating acute myeloid leukemia (AML), according to a study published in Cancer Research.

Investigators discovered that avocatin B, a lipid found in avocados, combats AML by targeting leukemia stem cells.

In in vitro experiments, avocatin B proved cytotoxic to AML stem and progenitor cells but did not affect normal hematopoietic stem cells.

“We’ve performed many rounds of testing to determine how this new drug works at a molecular level and confirmed that it targets stem cells selectively, leaving healthy cells unharmed,” said study author Paul Spagnuolo, PhD, of the University of Waterloo in Ontario, Canada.

Dr Spagnuolo and his colleagues performed a screen of a natural health product library to identify avocatin B. Subsequent experiments showed that avocatin B employs a novel mechanism to induce death in leukemic cells.

Avocatin B induces mitochondria-mediated apoptosis. The mitochondrial localization of avocatin B inhibits fatty acid oxidation and decreases levels of nicotinamide adenine dinucleotide phosphate, which results in elevated reactive oxygen species and leads to apoptosis.

Next steps

Through a partnership with the Centre for Commercialization of Regenerative Medicine, Dr Spagnuolo has filed a patent application for the use of avocatin B to treat AML. He is also performing experiments to prepare the drug for a phase 1 trial.

Dr Spagnuolo said there are other potential applications for avocatin B beyond oncology, and the drug is one of several compounds he and his team have isolated from a library of nutraceuticals. Some labs use food or plant extracts to develop nutraceuticals, but Dr Spagnuolo said he prefers the precision of using nutraceuticals with defined structures.

“Extracts are less refined,” he said. “The contents of an extract can vary from plant to plant and year to year, depending on lots of factors—on the soil, the location, the amount of sunlight, the rain.”

“Evaluating a nutraceutical as a potential clinical drug requires in-depth evaluation at the molecular level. This approach provides a clearer understanding of how the nutraceutical works, and it means we can reproduce the effects more accurately and consistently. This is critical to safely translating our lab work into a reliable drug that could be used in oncology clinics.”

Paul Spagnuolo, PhD, in the

lab, surrounded by avocados

Photo by Light Imaging/

University of Waterloo

A compound derived from avocados could be effective in treating acute myeloid leukemia (AML), according to a study published in Cancer Research.

Investigators discovered that avocatin B, a lipid found in avocados, combats AML by targeting leukemia stem cells.

In in vitro experiments, avocatin B proved cytotoxic to AML stem and progenitor cells but did not affect normal hematopoietic stem cells.

“We’ve performed many rounds of testing to determine how this new drug works at a molecular level and confirmed that it targets stem cells selectively, leaving healthy cells unharmed,” said study author Paul Spagnuolo, PhD, of the University of Waterloo in Ontario, Canada.

Dr Spagnuolo and his colleagues performed a screen of a natural health product library to identify avocatin B. Subsequent experiments showed that avocatin B employs a novel mechanism to induce death in leukemic cells.

Avocatin B induces mitochondria-mediated apoptosis. The mitochondrial localization of avocatin B inhibits fatty acid oxidation and decreases levels of nicotinamide adenine dinucleotide phosphate, which results in elevated reactive oxygen species and leads to apoptosis.

Next steps

Through a partnership with the Centre for Commercialization of Regenerative Medicine, Dr Spagnuolo has filed a patent application for the use of avocatin B to treat AML. He is also performing experiments to prepare the drug for a phase 1 trial.

Dr Spagnuolo said there are other potential applications for avocatin B beyond oncology, and the drug is one of several compounds he and his team have isolated from a library of nutraceuticals. Some labs use food or plant extracts to develop nutraceuticals, but Dr Spagnuolo said he prefers the precision of using nutraceuticals with defined structures.

“Extracts are less refined,” he said. “The contents of an extract can vary from plant to plant and year to year, depending on lots of factors—on the soil, the location, the amount of sunlight, the rain.”

“Evaluating a nutraceutical as a potential clinical drug requires in-depth evaluation at the molecular level. This approach provides a clearer understanding of how the nutraceutical works, and it means we can reproduce the effects more accurately and consistently. This is critical to safely translating our lab work into a reliable drug that could be used in oncology clinics.”

Paul Spagnuolo, PhD, in the

lab, surrounded by avocados

Photo by Light Imaging/

University of Waterloo

A compound derived from avocados could be effective in treating acute myeloid leukemia (AML), according to a study published in Cancer Research.

Investigators discovered that avocatin B, a lipid found in avocados, combats AML by targeting leukemia stem cells.

In in vitro experiments, avocatin B proved cytotoxic to AML stem and progenitor cells but did not affect normal hematopoietic stem cells.

“We’ve performed many rounds of testing to determine how this new drug works at a molecular level and confirmed that it targets stem cells selectively, leaving healthy cells unharmed,” said study author Paul Spagnuolo, PhD, of the University of Waterloo in Ontario, Canada.

Dr Spagnuolo and his colleagues performed a screen of a natural health product library to identify avocatin B. Subsequent experiments showed that avocatin B employs a novel mechanism to induce death in leukemic cells.

Avocatin B induces mitochondria-mediated apoptosis. The mitochondrial localization of avocatin B inhibits fatty acid oxidation and decreases levels of nicotinamide adenine dinucleotide phosphate, which results in elevated reactive oxygen species and leads to apoptosis.

Next steps

Through a partnership with the Centre for Commercialization of Regenerative Medicine, Dr Spagnuolo has filed a patent application for the use of avocatin B to treat AML. He is also performing experiments to prepare the drug for a phase 1 trial.

Dr Spagnuolo said there are other potential applications for avocatin B beyond oncology, and the drug is one of several compounds he and his team have isolated from a library of nutraceuticals. Some labs use food or plant extracts to develop nutraceuticals, but Dr Spagnuolo said he prefers the precision of using nutraceuticals with defined structures.

“Extracts are less refined,” he said. “The contents of an extract can vary from plant to plant and year to year, depending on lots of factors—on the soil, the location, the amount of sunlight, the rain.”

“Evaluating a nutraceutical as a potential clinical drug requires in-depth evaluation at the molecular level. This approach provides a clearer understanding of how the nutraceutical works, and it means we can reproduce the effects more accurately and consistently. This is critical to safely translating our lab work into a reliable drug that could be used in oncology clinics.”

DNA helix

Image by Spencer Phillips

A new algorithm makes it possible to perform genetic analyses on as many as 500,000 individuals—and many traits—at the same time, according to an article in Nature Methods.

The authors noted that determining how genetic variations affect health and disease involves analyzing associations between many different variants and multiple traits and making the best use of data from large cohorts that include hundreds of thousands of individuals.

“It is very challenging to identify genetic variants that underlie phenotypes, or traits, and, usually, we do this by analyzing each phenotype and each variant one by one,” explained Oliver Stegle, PhD, of the European Molecular Biology Laboratory-European Bioinformatics Institute in Cambridge, UK.

“But the simple models we use to do this are too simplistic to uncover the complex dependencies between sets of genetic variants and disease phenotypes.”

On the other hand, complex models that reveal the combined action of many different variants have involved so much computation that it would take a year to run a single complex query. But Dr Stegle and his colleagues said their algorithm can change that.

“The breakthrough here is that we’ve made it possible to perform an integrative analysis involving many variants and phenotypes at the same speed as current approaches,” Dr Stegle said.

He and his colleagues tested their new method, called mtSet, on data from 2 studies and compared the results with existing tools used for genetic analysis. The researchers found that mtSet was substantially faster than existing methods and could explain a larger proportion of traits in terms of the genetics that drive them.

The team said mtSet will allow researchers to explore several variants of a gene at once, while comparing them with several related phenotypes. This makes it easier to pinpoint which genes—or locations on genes—are involved in a particular function.

“What’s important about this work is that it improves statistical power and provides the tools people need to analyze multiple traits in very large cohorts,” Dr Stegle said. “Our algorithm can be used to study up to half a million individuals. That hasn’t been possible until now.”

DNA helix

Image by Spencer Phillips

A new algorithm makes it possible to perform genetic analyses on as many as 500,000 individuals—and many traits—at the same time, according to an article in Nature Methods.

The authors noted that determining how genetic variations affect health and disease involves analyzing associations between many different variants and multiple traits and making the best use of data from large cohorts that include hundreds of thousands of individuals.

“It is very challenging to identify genetic variants that underlie phenotypes, or traits, and, usually, we do this by analyzing each phenotype and each variant one by one,” explained Oliver Stegle, PhD, of the European Molecular Biology Laboratory-European Bioinformatics Institute in Cambridge, UK.

“But the simple models we use to do this are too simplistic to uncover the complex dependencies between sets of genetic variants and disease phenotypes.”

On the other hand, complex models that reveal the combined action of many different variants have involved so much computation that it would take a year to run a single complex query. But Dr Stegle and his colleagues said their algorithm can change that.

“The breakthrough here is that we’ve made it possible to perform an integrative analysis involving many variants and phenotypes at the same speed as current approaches,” Dr Stegle said.

He and his colleagues tested their new method, called mtSet, on data from 2 studies and compared the results with existing tools used for genetic analysis. The researchers found that mtSet was substantially faster than existing methods and could explain a larger proportion of traits in terms of the genetics that drive them.

The team said mtSet will allow researchers to explore several variants of a gene at once, while comparing them with several related phenotypes. This makes it easier to pinpoint which genes—or locations on genes—are involved in a particular function.

“What’s important about this work is that it improves statistical power and provides the tools people need to analyze multiple traits in very large cohorts,” Dr Stegle said. “Our algorithm can be used to study up to half a million individuals. That hasn’t been possible until now.”

DNA helix

Image by Spencer Phillips

A new algorithm makes it possible to perform genetic analyses on as many as 500,000 individuals—and many traits—at the same time, according to an article in Nature Methods.

The authors noted that determining how genetic variations affect health and disease involves analyzing associations between many different variants and multiple traits and making the best use of data from large cohorts that include hundreds of thousands of individuals.

“It is very challenging to identify genetic variants that underlie phenotypes, or traits, and, usually, we do this by analyzing each phenotype and each variant one by one,” explained Oliver Stegle, PhD, of the European Molecular Biology Laboratory-European Bioinformatics Institute in Cambridge, UK.

“But the simple models we use to do this are too simplistic to uncover the complex dependencies between sets of genetic variants and disease phenotypes.”

On the other hand, complex models that reveal the combined action of many different variants have involved so much computation that it would take a year to run a single complex query. But Dr Stegle and his colleagues said their algorithm can change that.

“The breakthrough here is that we’ve made it possible to perform an integrative analysis involving many variants and phenotypes at the same speed as current approaches,” Dr Stegle said.

He and his colleagues tested their new method, called mtSet, on data from 2 studies and compared the results with existing tools used for genetic analysis. The researchers found that mtSet was substantially faster than existing methods and could explain a larger proportion of traits in terms of the genetics that drive them.

The team said mtSet will allow researchers to explore several variants of a gene at once, while comparing them with several related phenotypes. This makes it easier to pinpoint which genes—or locations on genes—are involved in a particular function.

“What’s important about this work is that it improves statistical power and provides the tools people need to analyze multiple traits in very large cohorts,” Dr Stegle said. “Our algorithm can be used to study up to half a million individuals. That hasn’t been possible until now.”

Researchers in the lab

Photo by Rhoda Baer

ROME, ITALY—Interleukin-1β (IL-1β) is a crucial factor in the development of blood-induced cartilage damage, according to research presented at the European League Against Rheumatism Annual Congress (EULAR 2015).

This discovery suggests that therapeutically targeting IL-1β could provide a new way to protect cartilage after a joint bleed, which can occur after joint trauma, major joint surgery, or due to hemophilia.

Whatever the cause, joint bleeds are expected to lead to an inflammatory response in the joint and to significant destruction of joint cartilage. So a treatment that could limit the damage from a joint bleed could potentially minimize future disability.

“As therapeutic agents opposing the activity of IL-1β are readily available, further research is now warranted to investigate whether an IL-1β antagonist would be effective in preventing and treating joint damage as a result of bleeding into the joint,” said study investigator Simon Mastbergen, PhD, of the University Medical Centre Utrecht in the Netherlands.

“Findings also suggest that the quicker treatment is initiated, the less damage to the joint may be sustained.”

Dr Mastbergen and his colleagues presented these findings at EULAR 2015 as abstract OP0262.

The researchers had cultured healthy human cartilage samples for 4 days in the presence or absence of 50% whole blood. They then added an IL-1β monoclonal antibody (mAb), an IL-1 receptor antagonist (IL-1RA), or a TNF-α mAb during blood exposure and assessed subsequent cartilage damage.

The IL-1β mAb and IL-1RA protected cartilage from blood-induced damage in a dose- and time-dependent manner. Early administration after blood exposure was the most beneficial. And, when the treatments were given at higher concentrations, there was near-complete normalization of cartilage.

The researchers said these effects were accompanied by a reduction in IL-1β and IL-6 production. The level of IL-1β was 74 pg/mL in whole-blood culture, but levels were undetectable after the IL-1RA was added (P=0.028). The level of IL-6 was 21,347 pg/mL in whole-blood culture, 27 pg/mL after the IL-1RA was added, and 289 pg/mL after the IL-1β mAb was added (P=0.028 for both).

However, TNF-α levels were unaffected by the IL-1RA or IL-1β mAb. TNF-α levels wer 35 pg/mL in whole-blood culture and 37 pg/mL after the addition of the IL-1RA or IL-1β mAb (P=0.753 for both).

Of course, the TNF-α mAb inhibited the effects of TNF-α on cartilage, but the mAb had no significant effect on blood-induced cartilage damage.

“This would appear to rule out TNF-α inhibitors, a class of drug currently used to treat various forms of arthritis, for this new indication,” Dr Mastbergen said.

Researchers in the lab

Photo by Rhoda Baer

ROME, ITALY—Interleukin-1β (IL-1β) is a crucial factor in the development of blood-induced cartilage damage, according to research presented at the European League Against Rheumatism Annual Congress (EULAR 2015).

This discovery suggests that therapeutically targeting IL-1β could provide a new way to protect cartilage after a joint bleed, which can occur after joint trauma, major joint surgery, or due to hemophilia.

Whatever the cause, joint bleeds are expected to lead to an inflammatory response in the joint and to significant destruction of joint cartilage. So a treatment that could limit the damage from a joint bleed could potentially minimize future disability.

“As therapeutic agents opposing the activity of IL-1β are readily available, further research is now warranted to investigate whether an IL-1β antagonist would be effective in preventing and treating joint damage as a result of bleeding into the joint,” said study investigator Simon Mastbergen, PhD, of the University Medical Centre Utrecht in the Netherlands.

“Findings also suggest that the quicker treatment is initiated, the less damage to the joint may be sustained.”

Dr Mastbergen and his colleagues presented these findings at EULAR 2015 as abstract OP0262.

The researchers had cultured healthy human cartilage samples for 4 days in the presence or absence of 50% whole blood. They then added an IL-1β monoclonal antibody (mAb), an IL-1 receptor antagonist (IL-1RA), or a TNF-α mAb during blood exposure and assessed subsequent cartilage damage.

The IL-1β mAb and IL-1RA protected cartilage from blood-induced damage in a dose- and time-dependent manner. Early administration after blood exposure was the most beneficial. And, when the treatments were given at higher concentrations, there was near-complete normalization of cartilage.

The researchers said these effects were accompanied by a reduction in IL-1β and IL-6 production. The level of IL-1β was 74 pg/mL in whole-blood culture, but levels were undetectable after the IL-1RA was added (P=0.028). The level of IL-6 was 21,347 pg/mL in whole-blood culture, 27 pg/mL after the IL-1RA was added, and 289 pg/mL after the IL-1β mAb was added (P=0.028 for both).

However, TNF-α levels were unaffected by the IL-1RA or IL-1β mAb. TNF-α levels wer 35 pg/mL in whole-blood culture and 37 pg/mL after the addition of the IL-1RA or IL-1β mAb (P=0.753 for both).

Of course, the TNF-α mAb inhibited the effects of TNF-α on cartilage, but the mAb had no significant effect on blood-induced cartilage damage.

“This would appear to rule out TNF-α inhibitors, a class of drug currently used to treat various forms of arthritis, for this new indication,” Dr Mastbergen said.

Researchers in the lab

Photo by Rhoda Baer

ROME, ITALY—Interleukin-1β (IL-1β) is a crucial factor in the development of blood-induced cartilage damage, according to research presented at the European League Against Rheumatism Annual Congress (EULAR 2015).

This discovery suggests that therapeutically targeting IL-1β could provide a new way to protect cartilage after a joint bleed, which can occur after joint trauma, major joint surgery, or due to hemophilia.

Whatever the cause, joint bleeds are expected to lead to an inflammatory response in the joint and to significant destruction of joint cartilage. So a treatment that could limit the damage from a joint bleed could potentially minimize future disability.

“As therapeutic agents opposing the activity of IL-1β are readily available, further research is now warranted to investigate whether an IL-1β antagonist would be effective in preventing and treating joint damage as a result of bleeding into the joint,” said study investigator Simon Mastbergen, PhD, of the University Medical Centre Utrecht in the Netherlands.

“Findings also suggest that the quicker treatment is initiated, the less damage to the joint may be sustained.”

Dr Mastbergen and his colleagues presented these findings at EULAR 2015 as abstract OP0262.

The researchers had cultured healthy human cartilage samples for 4 days in the presence or absence of 50% whole blood. They then added an IL-1β monoclonal antibody (mAb), an IL-1 receptor antagonist (IL-1RA), or a TNF-α mAb during blood exposure and assessed subsequent cartilage damage.

The IL-1β mAb and IL-1RA protected cartilage from blood-induced damage in a dose- and time-dependent manner. Early administration after blood exposure was the most beneficial. And, when the treatments were given at higher concentrations, there was near-complete normalization of cartilage.

The researchers said these effects were accompanied by a reduction in IL-1β and IL-6 production. The level of IL-1β was 74 pg/mL in whole-blood culture, but levels were undetectable after the IL-1RA was added (P=0.028). The level of IL-6 was 21,347 pg/mL in whole-blood culture, 27 pg/mL after the IL-1RA was added, and 289 pg/mL after the IL-1β mAb was added (P=0.028 for both).

However, TNF-α levels were unaffected by the IL-1RA or IL-1β mAb. TNF-α levels wer 35 pg/mL in whole-blood culture and 37 pg/mL after the addition of the IL-1RA or IL-1β mAb (P=0.753 for both).

Of course, the TNF-α mAb inhibited the effects of TNF-α on cartilage, but the mAb had no significant effect on blood-induced cartilage damage.

“This would appear to rule out TNF-α inhibitors, a class of drug currently used to treat various forms of arthritis, for this new indication,” Dr Mastbergen said.

Anopheles gambiae mosquito

Photo courtesy of the CDC

Researchers say they have located a new, more precise target for a mosquito-based vaccine to block the transmission of malaria.

The team created a 3-D crystal structure of AnAPN1, a protein found in the gut of the Anopheles mosquito that is considered essential to malaria transmission.

In studying the entire protein, the researchers found that previous incarnations of a proposed vaccine included irrelevant regions of AnAPN1.

Rhoel R. Dinglasan, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues described this work in Nature Structural & Molecular Biology.

AnAPN1 is found on the apical surface of the Anopheles gambiae midgut and is potentially a receptor for the Plasmodium parasite. As a vaccine antigen, AnAPN1 prompts antibody production, but only some of these antibodies block parasite transmission.

“This dilution of the overall antibody response to AnAPN1 is problematic,” Dr Dinglasan said. “To further improve vaccine immunogenicity at the preclinical stage, we need to immuno-focus the antibody response to only the critical, transmission-blocking regions of the protein.”

Using the Australian Synchrotron, the researchers were able to visualize the crystal structure of AnAPN1 for the first time. This allowed the team to pinpoint the binding site of AnAPN1 antibodies that can and cannot block parasite development.

“We now know much more about which parts of the AnAPN1 protein are involved in generating transmission-blocking antibodies and have a new hypothesis as to how they might work,” said Natalie Borg, PhD, of Monash University in Clayton, Victoria, Australia.

The researchers identified a particularly potent antibody, 4H5B7, and tested it in blood samples from children carrying the Plasmodium falciparum parasite. 4H5B7 exhibited “complete transmission-blocking activity” against these naturally circulating strains of P falciparum.

The team said their data indicate the mechanism underlying this activity is the recognition of a conformation-dependent epitope that is predominantly found on peptide 4, which is part of peptide 7 on domain 1 of AnAPN1.

These findings suggest that, previously, researchers were asking the immune system to target too many regions on AnAPN1, which diluted the response to the relevant regions of the protein.

Anopheles gambiae mosquito

Photo courtesy of the CDC

Researchers say they have located a new, more precise target for a mosquito-based vaccine to block the transmission of malaria.

The team created a 3-D crystal structure of AnAPN1, a protein found in the gut of the Anopheles mosquito that is considered essential to malaria transmission.

In studying the entire protein, the researchers found that previous incarnations of a proposed vaccine included irrelevant regions of AnAPN1.

Rhoel R. Dinglasan, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues described this work in Nature Structural & Molecular Biology.

AnAPN1 is found on the apical surface of the Anopheles gambiae midgut and is potentially a receptor for the Plasmodium parasite. As a vaccine antigen, AnAPN1 prompts antibody production, but only some of these antibodies block parasite transmission.

“This dilution of the overall antibody response to AnAPN1 is problematic,” Dr Dinglasan said. “To further improve vaccine immunogenicity at the preclinical stage, we need to immuno-focus the antibody response to only the critical, transmission-blocking regions of the protein.”

Using the Australian Synchrotron, the researchers were able to visualize the crystal structure of AnAPN1 for the first time. This allowed the team to pinpoint the binding site of AnAPN1 antibodies that can and cannot block parasite development.

“We now know much more about which parts of the AnAPN1 protein are involved in generating transmission-blocking antibodies and have a new hypothesis as to how they might work,” said Natalie Borg, PhD, of Monash University in Clayton, Victoria, Australia.

The researchers identified a particularly potent antibody, 4H5B7, and tested it in blood samples from children carrying the Plasmodium falciparum parasite. 4H5B7 exhibited “complete transmission-blocking activity” against these naturally circulating strains of P falciparum.

The team said their data indicate the mechanism underlying this activity is the recognition of a conformation-dependent epitope that is predominantly found on peptide 4, which is part of peptide 7 on domain 1 of AnAPN1.

These findings suggest that, previously, researchers were asking the immune system to target too many regions on AnAPN1, which diluted the response to the relevant regions of the protein.

Anopheles gambiae mosquito

Photo courtesy of the CDC

Researchers say they have located a new, more precise target for a mosquito-based vaccine to block the transmission of malaria.

The team created a 3-D crystal structure of AnAPN1, a protein found in the gut of the Anopheles mosquito that is considered essential to malaria transmission.

In studying the entire protein, the researchers found that previous incarnations of a proposed vaccine included irrelevant regions of AnAPN1.

Rhoel R. Dinglasan, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues described this work in Nature Structural & Molecular Biology.

AnAPN1 is found on the apical surface of the Anopheles gambiae midgut and is potentially a receptor for the Plasmodium parasite. As a vaccine antigen, AnAPN1 prompts antibody production, but only some of these antibodies block parasite transmission.

“This dilution of the overall antibody response to AnAPN1 is problematic,” Dr Dinglasan said. “To further improve vaccine immunogenicity at the preclinical stage, we need to immuno-focus the antibody response to only the critical, transmission-blocking regions of the protein.”

Using the Australian Synchrotron, the researchers were able to visualize the crystal structure of AnAPN1 for the first time. This allowed the team to pinpoint the binding site of AnAPN1 antibodies that can and cannot block parasite development.

“We now know much more about which parts of the AnAPN1 protein are involved in generating transmission-blocking antibodies and have a new hypothesis as to how they might work,” said Natalie Borg, PhD, of Monash University in Clayton, Victoria, Australia.

The researchers identified a particularly potent antibody, 4H5B7, and tested it in blood samples from children carrying the Plasmodium falciparum parasite. 4H5B7 exhibited “complete transmission-blocking activity” against these naturally circulating strains of P falciparum.

The team said their data indicate the mechanism underlying this activity is the recognition of a conformation-dependent epitope that is predominantly found on peptide 4, which is part of peptide 7 on domain 1 of AnAPN1.

These findings suggest that, previously, researchers were asking the immune system to target too many regions on AnAPN1, which diluted the response to the relevant regions of the protein.

The lead author of a new Journal of Hospital Medicine report says one step hospitalists can take toward reducing preventable rehospitalizations is identifying the common traits of frequently admitted patients.

Marilyn Szekendi, PhD, RN, director of quality research at University Health System Consortium (UHC) in Chicago, says learning the characteristics that lead to frequent admissions—defined as patients who are admitted five or more times within one year—can help identify solutions for preventing repeated hospitalizations. UHC is an alliance of nonprofit academic medical centers and their affiliated hospitals.

"The good news here is that this is very doable," Dr. Szekendi says. "Every hospital can run this analysis…and actually create a list of who these patients are, along with their names and medical record numbers, so you can look at their diagnosis, you can look at other characteristics of the patient, and do a real-time assessment of who they are."

For their report, Dr. Szekendi and colleagues studied 28,291 patients admitted 180,185 times to academic medical centers in the U.S. from 2011 to 2012. While the cohort comprised just 1.6% of all patients, it accounted for 8% of all admissions and 7% of direct costs.

Common factors linked with frequent readmissions included having significantly more comorbidities (an average of 7.1 versus 2.5), and 84% of their admissions are to medical services. In addition, this patient population has higher rates of psychosis or substance abuse, the researchers note. Although frequently admitted patients are slightly more likely than other patients to be on Medicaid or to be uninsured (27.6% versus 21.6%), nearly three-quarters have private or Medicare coverage.

"We know that there are many other factors that we didn't have data for, [such as] housing status, patients' preexisting access to other kinds of medical care," Dr. Szekendi says. "If we could do some further look at factors that define these patients, both nationally and individually, hospitals then would have some additional, really useful information about the patients that would further inform their improvement efforts. Going beyond the data...is the next step.”

Visit our website for more information on hospitalists' role in preventing readmissions.

The lead author of a new Journal of Hospital Medicine report says one step hospitalists can take toward reducing preventable rehospitalizations is identifying the common traits of frequently admitted patients.

Marilyn Szekendi, PhD, RN, director of quality research at University Health System Consortium (UHC) in Chicago, says learning the characteristics that lead to frequent admissions—defined as patients who are admitted five or more times within one year—can help identify solutions for preventing repeated hospitalizations. UHC is an alliance of nonprofit academic medical centers and their affiliated hospitals.

"The good news here is that this is very doable," Dr. Szekendi says. "Every hospital can run this analysis…and actually create a list of who these patients are, along with their names and medical record numbers, so you can look at their diagnosis, you can look at other characteristics of the patient, and do a real-time assessment of who they are."

For their report, Dr. Szekendi and colleagues studied 28,291 patients admitted 180,185 times to academic medical centers in the U.S. from 2011 to 2012. While the cohort comprised just 1.6% of all patients, it accounted for 8% of all admissions and 7% of direct costs.

Common factors linked with frequent readmissions included having significantly more comorbidities (an average of 7.1 versus 2.5), and 84% of their admissions are to medical services. In addition, this patient population has higher rates of psychosis or substance abuse, the researchers note. Although frequently admitted patients are slightly more likely than other patients to be on Medicaid or to be uninsured (27.6% versus 21.6%), nearly three-quarters have private or Medicare coverage.

"We know that there are many other factors that we didn't have data for, [such as] housing status, patients' preexisting access to other kinds of medical care," Dr. Szekendi says. "If we could do some further look at factors that define these patients, both nationally and individually, hospitals then would have some additional, really useful information about the patients that would further inform their improvement efforts. Going beyond the data...is the next step.”

Visit our website for more information on hospitalists' role in preventing readmissions.

The lead author of a new Journal of Hospital Medicine report says one step hospitalists can take toward reducing preventable rehospitalizations is identifying the common traits of frequently admitted patients.

Marilyn Szekendi, PhD, RN, director of quality research at University Health System Consortium (UHC) in Chicago, says learning the characteristics that lead to frequent admissions—defined as patients who are admitted five or more times within one year—can help identify solutions for preventing repeated hospitalizations. UHC is an alliance of nonprofit academic medical centers and their affiliated hospitals.

"The good news here is that this is very doable," Dr. Szekendi says. "Every hospital can run this analysis…and actually create a list of who these patients are, along with their names and medical record numbers, so you can look at their diagnosis, you can look at other characteristics of the patient, and do a real-time assessment of who they are."

For their report, Dr. Szekendi and colleagues studied 28,291 patients admitted 180,185 times to academic medical centers in the U.S. from 2011 to 2012. While the cohort comprised just 1.6% of all patients, it accounted for 8% of all admissions and 7% of direct costs.

Common factors linked with frequent readmissions included having significantly more comorbidities (an average of 7.1 versus 2.5), and 84% of their admissions are to medical services. In addition, this patient population has higher rates of psychosis or substance abuse, the researchers note. Although frequently admitted patients are slightly more likely than other patients to be on Medicaid or to be uninsured (27.6% versus 21.6%), nearly three-quarters have private or Medicare coverage.

"We know that there are many other factors that we didn't have data for, [such as] housing status, patients' preexisting access to other kinds of medical care," Dr. Szekendi says. "If we could do some further look at factors that define these patients, both nationally and individually, hospitals then would have some additional, really useful information about the patients that would further inform their improvement efforts. Going beyond the data...is the next step.”

Visit our website for more information on hospitalists' role in preventing readmissions.

Clinical question: What is the impact of statin discontinuation in palliative care setting?

Background: There is compelling evidence for prescribing statins for primary or secondary prevention of cardiovascular disease for patients with long life expectancy, but there is no evidence to guide decisions to discontinue therapy in those with limited prognosis.

Study design: Multicenter, unblinded, randomized, and pragmatic clinical trial.

Setting: Academic and community-based clinical sites as a part of the Palliative Care Research Cooperative Group.

Synopsis: The study analyzed the outcomes of 381 patients who had received a prognosis of one-month to one-year life expectancy, with an average age of 74. The participants were divided into two groups: continued statin group and discontinued statin group. Of the 381 participants, 212 survived beyond 60 days.

There was no significant difference between the proportion of participants who died within 60 days, with 45 (23.8%) in the discontinued statin group and 39 (20.3%) in the continued statin group (90% Cl, -3.5%–10.5%; P=0.36). Total quality of life was better for the group discontinuing statin therapy (mean McGill QOL score 7.11 versus 6.85; P=0.04). The researchers estimated that surviving participants would save $3.37 per day and $716 per patient.

Because of a lack of formal guidelines for discontinuation of statin therapy in patients with life-limiting illness, the discontinuation of statin therapy is mostly based on patient-provider decisions.

The results from this study will help physicians have thoughtful patient-provider discussions regarding statin discontinuation.

Citation: Kutner JS, Blatchford PJ, Taylor DH Jr, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015;175(5):691–700. doi:10.1001/jamainternmed.2015.0289.

Visit our website for more research reviews.

Clinical question: What is the impact of statin discontinuation in palliative care setting?

Background: There is compelling evidence for prescribing statins for primary or secondary prevention of cardiovascular disease for patients with long life expectancy, but there is no evidence to guide decisions to discontinue therapy in those with limited prognosis.

Study design: Multicenter, unblinded, randomized, and pragmatic clinical trial.

Setting: Academic and community-based clinical sites as a part of the Palliative Care Research Cooperative Group.

Synopsis: The study analyzed the outcomes of 381 patients who had received a prognosis of one-month to one-year life expectancy, with an average age of 74. The participants were divided into two groups: continued statin group and discontinued statin group. Of the 381 participants, 212 survived beyond 60 days.

There was no significant difference between the proportion of participants who died within 60 days, with 45 (23.8%) in the discontinued statin group and 39 (20.3%) in the continued statin group (90% Cl, -3.5%–10.5%; P=0.36). Total quality of life was better for the group discontinuing statin therapy (mean McGill QOL score 7.11 versus 6.85; P=0.04). The researchers estimated that surviving participants would save $3.37 per day and $716 per patient.

Because of a lack of formal guidelines for discontinuation of statin therapy in patients with life-limiting illness, the discontinuation of statin therapy is mostly based on patient-provider decisions.

The results from this study will help physicians have thoughtful patient-provider discussions regarding statin discontinuation.

Citation: Kutner JS, Blatchford PJ, Taylor DH Jr, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015;175(5):691–700. doi:10.1001/jamainternmed.2015.0289.

Visit our website for more research reviews.

Clinical question: What is the impact of statin discontinuation in palliative care setting?

Background: There is compelling evidence for prescribing statins for primary or secondary prevention of cardiovascular disease for patients with long life expectancy, but there is no evidence to guide decisions to discontinue therapy in those with limited prognosis.

Study design: Multicenter, unblinded, randomized, and pragmatic clinical trial.

Setting: Academic and community-based clinical sites as a part of the Palliative Care Research Cooperative Group.

Synopsis: The study analyzed the outcomes of 381 patients who had received a prognosis of one-month to one-year life expectancy, with an average age of 74. The participants were divided into two groups: continued statin group and discontinued statin group. Of the 381 participants, 212 survived beyond 60 days.

There was no significant difference between the proportion of participants who died within 60 days, with 45 (23.8%) in the discontinued statin group and 39 (20.3%) in the continued statin group (90% Cl, -3.5%–10.5%; P=0.36). Total quality of life was better for the group discontinuing statin therapy (mean McGill QOL score 7.11 versus 6.85; P=0.04). The researchers estimated that surviving participants would save $3.37 per day and $716 per patient.

Because of a lack of formal guidelines for discontinuation of statin therapy in patients with life-limiting illness, the discontinuation of statin therapy is mostly based on patient-provider decisions.

The results from this study will help physicians have thoughtful patient-provider discussions regarding statin discontinuation.

Citation: Kutner JS, Blatchford PJ, Taylor DH Jr, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015;175(5):691–700. doi:10.1001/jamainternmed.2015.0289.

Visit our website for more research reviews.

The Internet has changed many facets of modern life, and the practice of medicine has not gone untouched. Consider, for better or worse, the reliance of many patients on WebMD and various other sites for self-diagnosis before consulting with a physician. Even before the Internet, patients would self-diagnose their skin type (more than 80% of them get it wrong). The Internet allows them access to most cosmeceutical brands, the misuse of which leads to unintended consequences that can affect skin health. Clearly, patients who receive advice from a trained medical professional have better outcomes. One reason for this is that the doctor (or aesthetician) spends time with the patient, explaining what products to use and in which order to use them, and follows up with the patient to assess the outcome and adjust the regimen as needed. The problem arises when these patients decide to purchase the products from a source other than their treating physician. Only about 30% of patients buy refills from their doctor for second purchases, and just 15% purchase products from their doctor the third time around. Why is this? It is likely the convenience and the low cost that drive patients to purchase from sources other than their physician or aesthetician. This desire to save money carries significant risks. Many the products online are expired or counterfeit, or are old containers refilled with a different formulation. Patients should be cautioned to only buy products from a source they trust.

I have had dozens of patients bringing in counterfeit products in the last few months. It seems that the problem is becoming more common. I interviewed several companies about this to see whether others were experiencing the same trend. This is what I found:

Some companies report that they have seen their samples and trade size containers being sold on eBay. Joe Ragosta of Topix Pharmaceuticals reports that when his company has asked such sellers if they are obtaining these products – marked as samples – from the company, they hear a range of defensive responses, including: “I got it at a show” or “My doctor gave me samples, and I decided to sell them” and “I work at a doctor’s office, and they let me take products as needed.” Make sure that no one on your staff is taking samples and selling them online.

One example: NeoStrata is concerned about the fraudulent use of their products. They recommend that patients purchase their products only from a known physician, ideally from the physician’s office rather than the website. The company understands that customers may want to save money wherever they can and might prefer to buy products online. NeoStrata urges customers who opt to buy online to make such purchases through physician-affiliated websites, where the doctor is clearly identified. At the very least, the company urges patients to choose only sites where they can contact someone and obtain the name of a physician. Further, they strongly discourage using eBay or other auction sites, which do not vouch for the safety and authenticity of products sold through their services.

Other potential problems with skin care products sold online include the following.

Counterfeit products

Several reports have indicated that counterfeit skin products originating in other countries have made their way into the United States and, according to the article published on the website Fact Based Skin Care, pharmaceuticals and personal care products, including cosmetics, are among the top five types of products seized by U.S. Customs and Border Patrol agents (Coy, C. Dangers of Counterfeit Cosmetics, Aug. 4, 2014). Such products include old bottles refilled with inexpensive imitation creams or bottles made to look like legitimate products that in fact contain imitation creams. I once had a patient present with an adverse reaction to a retinol product, which she brought with her to the visit. I sent the bottle to the company, which confirmed my suspicion that the product was counterfeit – a different bottle with a similar label.

In February 2014, CBS New York ran a segment on the potential inclusion of carcinogenic and other harmful ingredients found in online personal care products touted for their low prices (CBS New York. Counterfeit Cosmetics May Be Harmful To Your Health. Feb. 27, 2014). Not even 2 weeks later, CNN reported on the arrest of two brothers in New York alleged to have masterminded a multimillion-dollar counterfeit health and beauty product ring (CNN. Zulueta A. Massive Fake Health and Beauty Supplies Ring Busted. March 9, 2014). ABC’s Good Morning America followed suit with a segment in April 2014 that exposed aspects of the use of knock-off cosmetic products (ABC News, Good Morning America. Online Beauty Bargains: Is It the Real Deal? April 3, 2014).

The Federal Bureau of Investigation has posted memos concerning counterfeit and potentially compromised and hazardous cosmetics and fragrances, offering tips aimed at readily identifying or avoiding unauthorized products.

Torie Hardee of EltaMD summarized that counterfeit products can sometimes be identified by lack of an expiration date on the bottle, discoloration or slightly different fonts on bottles and packaging, and the manufacturer’s address on the bottle.

Jan Marini Company representative Stuart Mohr noted that their company has received returns of products that they had not manufactured, as well as their own current or discontinued products returned years after the expiration date. The Jan Marini Co., and most other companies, will not guarantee any product purchased via nonauthorized resellers, because the authenticity and safety of such products cannot be verified.

“These unauthorized resellers are sophisticated, often even working in rings, and find it easy to hide their real identity,” said Mr. Mohr. “Addresses are often hidden or vague; emails are not linked to any specific person; and it’s easy to use false names. If a person is caught in an unauthorized online transaction, it’s easy to change the email address or name and start again,” he added.

©Ingram Publishing/Thinkstockphotos.com

FBI’s tips for spotting counterfeit cosmetics and fragrances

• The product is a sample size.

• The packaging differs slightly from the authentic brand (different color or font).

• The product’s wrapping appears haphazard.

• The product is being advertised as a “limited edition” even though the authentic manufacturer doesn’t offer it as a limited edition.

• The product is not listed on the manufacturer’s website.

• The price is drastically lower than the MSRP.

• The product’s consistency or texture doesn’t feel or look like the authentic brand.

• For fragrances, something seems off about the scent, and the color of the fluid in the bottle might be different than the original.

• They are being sold at nonauthorized retailers, including flea markets and discount stores.

• The label does not contain lot number, bar code, manufacturer’s address, or expiration date.

Expired products

Unscrupulous online retailers may slash prices on expired products and remove the expiration date from the package. In my practice, a patient experiencing an erythematous reaction brought in the “SkinMedica” product bottle, which looked suspicious to me. The packaging that the product was in had been discontinued 8 years earlier. It is important to remember that ingredients, particularly retinol, degrade with exposure to air, sun, and heat, and over time. This is most likely what caused my patient’s adverse reaction, and her initial savings from the product caused her several weeks of irritated skin.

Diverted products

SkinMedica reports that diverted products are a trickier issue than counterfeit products, because their packaging and formulas are sufficiently complex to make counterfeiting too difficult to be profitable. Instead, their products have been sold on the so-called gray market below the manufacturer suggested retail price (MSRP), typically online. In these cases, the company cannot help patients with returns or complaints because they cannot verify the chain of custody of the purchased product. They are addressing this problem, though, with an awareness campaign called “Authentic and Authorized.” Its goal is to alert patients and the physicians who dispense their products of the benefits of a physician-dispensed model of skin care, with best outcomes achieved when doctors are prescribing a skin care regimen. SkinMedica emphasizes that no website can guarantee outcomes comparable to a skin care professional and product quality and safety can only be enforced when dispensed through authorized channels.

Potentially illegal or toxic ingredients

Several products that have entered the United States marketed as skin lighteners, antiaging agents, and acne treatment products have been found to contain mercury, according to a consumer update from the FDA. Arsenic, lead, beryllium, and other harmful toxins as well as allergy-inducing fragrances or preservatives not approved as safe in the U.S. may also be found in such products of dubious origin.

Improper storage

Products purveyed online are often stored in hot warehouses. As mentioned above, heat degrades and alters ingredients, rendering compounds such as retinol, benzoyl peroxide, peptides, and ascorbic acid worthless. Extreme cold can also damage the chemical integrity of products. Notably, organic products are more vulnerable because they lack preservatives to gird them against temperature variations and microbes that grow in hot, damp environments.

Lookalike imposters

Generic formulations are packaged to piggyback onto the success of well-known products. Such products found in drugstores may be packaged to look like Cetaphil or Aveeno items, but cost less, and deliver less. While the ingredients on the copycats are identical to those found in the branded preparations, the order in which ingredients are added, the temperature, pH, and even when and how fast ingredients are stirred are part of the proprietary recipe of the company and play a significant role in the potential of the end product and the actions the product exerts on the skin.

Conclusion

Whether or not you sell skin care products in your office, there is much you can do to educate your patients about skin care product safety. Namely, the farther a consumer gets from the source of the product or from reliable endorsers of products, the greater the opportunity for encountering fraudulent or counterfeit products. Patients are best served by sources they can trust, such as their dermatologist. If you sell products in your office, encourage your patients to buy refills from you so they can be assured of the proper formulations. Finally, encourage your patients not to skimp when it comes to the health of their skin, reminding them that it may cost them much more in terms of time, skin irritation, improper treatment, and all related expenses to buy products cheaply from unreliable sources.

Give your patients a copy of this article so that they will understand the enormity of the problem.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

The Internet has changed many facets of modern life, and the practice of medicine has not gone untouched. Consider, for better or worse, the reliance of many patients on WebMD and various other sites for self-diagnosis before consulting with a physician. Even before the Internet, patients would self-diagnose their skin type (more than 80% of them get it wrong). The Internet allows them access to most cosmeceutical brands, the misuse of which leads to unintended consequences that can affect skin health. Clearly, patients who receive advice from a trained medical professional have better outcomes. One reason for this is that the doctor (or aesthetician) spends time with the patient, explaining what products to use and in which order to use them, and follows up with the patient to assess the outcome and adjust the regimen as needed. The problem arises when these patients decide to purchase the products from a source other than their treating physician. Only about 30% of patients buy refills from their doctor for second purchases, and just 15% purchase products from their doctor the third time around. Why is this? It is likely the convenience and the low cost that drive patients to purchase from sources other than their physician or aesthetician. This desire to save money carries significant risks. Many the products online are expired or counterfeit, or are old containers refilled with a different formulation. Patients should be cautioned to only buy products from a source they trust.

I have had dozens of patients bringing in counterfeit products in the last few months. It seems that the problem is becoming more common. I interviewed several companies about this to see whether others were experiencing the same trend. This is what I found:

Some companies report that they have seen their samples and trade size containers being sold on eBay. Joe Ragosta of Topix Pharmaceuticals reports that when his company has asked such sellers if they are obtaining these products – marked as samples – from the company, they hear a range of defensive responses, including: “I got it at a show” or “My doctor gave me samples, and I decided to sell them” and “I work at a doctor’s office, and they let me take products as needed.” Make sure that no one on your staff is taking samples and selling them online.

One example: NeoStrata is concerned about the fraudulent use of their products. They recommend that patients purchase their products only from a known physician, ideally from the physician’s office rather than the website. The company understands that customers may want to save money wherever they can and might prefer to buy products online. NeoStrata urges customers who opt to buy online to make such purchases through physician-affiliated websites, where the doctor is clearly identified. At the very least, the company urges patients to choose only sites where they can contact someone and obtain the name of a physician. Further, they strongly discourage using eBay or other auction sites, which do not vouch for the safety and authenticity of products sold through their services.

Other potential problems with skin care products sold online include the following.

Counterfeit products

Several reports have indicated that counterfeit skin products originating in other countries have made their way into the United States and, according to the article published on the website Fact Based Skin Care, pharmaceuticals and personal care products, including cosmetics, are among the top five types of products seized by U.S. Customs and Border Patrol agents (Coy, C. Dangers of Counterfeit Cosmetics, Aug. 4, 2014). Such products include old bottles refilled with inexpensive imitation creams or bottles made to look like legitimate products that in fact contain imitation creams. I once had a patient present with an adverse reaction to a retinol product, which she brought with her to the visit. I sent the bottle to the company, which confirmed my suspicion that the product was counterfeit – a different bottle with a similar label.

In February 2014, CBS New York ran a segment on the potential inclusion of carcinogenic and other harmful ingredients found in online personal care products touted for their low prices (CBS New York. Counterfeit Cosmetics May Be Harmful To Your Health. Feb. 27, 2014). Not even 2 weeks later, CNN reported on the arrest of two brothers in New York alleged to have masterminded a multimillion-dollar counterfeit health and beauty product ring (CNN. Zulueta A. Massive Fake Health and Beauty Supplies Ring Busted. March 9, 2014). ABC’s Good Morning America followed suit with a segment in April 2014 that exposed aspects of the use of knock-off cosmetic products (ABC News, Good Morning America. Online Beauty Bargains: Is It the Real Deal? April 3, 2014).

The Federal Bureau of Investigation has posted memos concerning counterfeit and potentially compromised and hazardous cosmetics and fragrances, offering tips aimed at readily identifying or avoiding unauthorized products.

Torie Hardee of EltaMD summarized that counterfeit products can sometimes be identified by lack of an expiration date on the bottle, discoloration or slightly different fonts on bottles and packaging, and the manufacturer’s address on the bottle.

Jan Marini Company representative Stuart Mohr noted that their company has received returns of products that they had not manufactured, as well as their own current or discontinued products returned years after the expiration date. The Jan Marini Co., and most other companies, will not guarantee any product purchased via nonauthorized resellers, because the authenticity and safety of such products cannot be verified.

“These unauthorized resellers are sophisticated, often even working in rings, and find it easy to hide their real identity,” said Mr. Mohr. “Addresses are often hidden or vague; emails are not linked to any specific person; and it’s easy to use false names. If a person is caught in an unauthorized online transaction, it’s easy to change the email address or name and start again,” he added.

©Ingram Publishing/Thinkstockphotos.com

FBI’s tips for spotting counterfeit cosmetics and fragrances

• The product is a sample size.

• The packaging differs slightly from the authentic brand (different color or font).

• The product’s wrapping appears haphazard.

• The product is being advertised as a “limited edition” even though the authentic manufacturer doesn’t offer it as a limited edition.

• The product is not listed on the manufacturer’s website.

• The price is drastically lower than the MSRP.

• The product’s consistency or texture doesn’t feel or look like the authentic brand.

• For fragrances, something seems off about the scent, and the color of the fluid in the bottle might be different than the original.

• They are being sold at nonauthorized retailers, including flea markets and discount stores.

• The label does not contain lot number, bar code, manufacturer’s address, or expiration date.

Expired products

Unscrupulous online retailers may slash prices on expired products and remove the expiration date from the package. In my practice, a patient experiencing an erythematous reaction brought in the “SkinMedica” product bottle, which looked suspicious to me. The packaging that the product was in had been discontinued 8 years earlier. It is important to remember that ingredients, particularly retinol, degrade with exposure to air, sun, and heat, and over time. This is most likely what caused my patient’s adverse reaction, and her initial savings from the product caused her several weeks of irritated skin.

Diverted products

SkinMedica reports that diverted products are a trickier issue than counterfeit products, because their packaging and formulas are sufficiently complex to make counterfeiting too difficult to be profitable. Instead, their products have been sold on the so-called gray market below the manufacturer suggested retail price (MSRP), typically online. In these cases, the company cannot help patients with returns or complaints because they cannot verify the chain of custody of the purchased product. They are addressing this problem, though, with an awareness campaign called “Authentic and Authorized.” Its goal is to alert patients and the physicians who dispense their products of the benefits of a physician-dispensed model of skin care, with best outcomes achieved when doctors are prescribing a skin care regimen. SkinMedica emphasizes that no website can guarantee outcomes comparable to a skin care professional and product quality and safety can only be enforced when dispensed through authorized channels.

Potentially illegal or toxic ingredients

Several products that have entered the United States marketed as skin lighteners, antiaging agents, and acne treatment products have been found to contain mercury, according to a consumer update from the FDA. Arsenic, lead, beryllium, and other harmful toxins as well as allergy-inducing fragrances or preservatives not approved as safe in the U.S. may also be found in such products of dubious origin.

Improper storage

Products purveyed online are often stored in hot warehouses. As mentioned above, heat degrades and alters ingredients, rendering compounds such as retinol, benzoyl peroxide, peptides, and ascorbic acid worthless. Extreme cold can also damage the chemical integrity of products. Notably, organic products are more vulnerable because they lack preservatives to gird them against temperature variations and microbes that grow in hot, damp environments.

Lookalike imposters

Generic formulations are packaged to piggyback onto the success of well-known products. Such products found in drugstores may be packaged to look like Cetaphil or Aveeno items, but cost less, and deliver less. While the ingredients on the copycats are identical to those found in the branded preparations, the order in which ingredients are added, the temperature, pH, and even when and how fast ingredients are stirred are part of the proprietary recipe of the company and play a significant role in the potential of the end product and the actions the product exerts on the skin.

Conclusion

Whether or not you sell skin care products in your office, there is much you can do to educate your patients about skin care product safety. Namely, the farther a consumer gets from the source of the product or from reliable endorsers of products, the greater the opportunity for encountering fraudulent or counterfeit products. Patients are best served by sources they can trust, such as their dermatologist. If you sell products in your office, encourage your patients to buy refills from you so they can be assured of the proper formulations. Finally, encourage your patients not to skimp when it comes to the health of their skin, reminding them that it may cost them much more in terms of time, skin irritation, improper treatment, and all related expenses to buy products cheaply from unreliable sources.

Give your patients a copy of this article so that they will understand the enormity of the problem.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

The Internet has changed many facets of modern life, and the practice of medicine has not gone untouched. Consider, for better or worse, the reliance of many patients on WebMD and various other sites for self-diagnosis before consulting with a physician. Even before the Internet, patients would self-diagnose their skin type (more than 80% of them get it wrong). The Internet allows them access to most cosmeceutical brands, the misuse of which leads to unintended consequences that can affect skin health. Clearly, patients who receive advice from a trained medical professional have better outcomes. One reason for this is that the doctor (or aesthetician) spends time with the patient, explaining what products to use and in which order to use them, and follows up with the patient to assess the outcome and adjust the regimen as needed. The problem arises when these patients decide to purchase the products from a source other than their treating physician. Only about 30% of patients buy refills from their doctor for second purchases, and just 15% purchase products from their doctor the third time around. Why is this? It is likely the convenience and the low cost that drive patients to purchase from sources other than their physician or aesthetician. This desire to save money carries significant risks. Many the products online are expired or counterfeit, or are old containers refilled with a different formulation. Patients should be cautioned to only buy products from a source they trust.

I have had dozens of patients bringing in counterfeit products in the last few months. It seems that the problem is becoming more common. I interviewed several companies about this to see whether others were experiencing the same trend. This is what I found:

Some companies report that they have seen their samples and trade size containers being sold on eBay. Joe Ragosta of Topix Pharmaceuticals reports that when his company has asked such sellers if they are obtaining these products – marked as samples – from the company, they hear a range of defensive responses, including: “I got it at a show” or “My doctor gave me samples, and I decided to sell them” and “I work at a doctor’s office, and they let me take products as needed.” Make sure that no one on your staff is taking samples and selling them online.

One example: NeoStrata is concerned about the fraudulent use of their products. They recommend that patients purchase their products only from a known physician, ideally from the physician’s office rather than the website. The company understands that customers may want to save money wherever they can and might prefer to buy products online. NeoStrata urges customers who opt to buy online to make such purchases through physician-affiliated websites, where the doctor is clearly identified. At the very least, the company urges patients to choose only sites where they can contact someone and obtain the name of a physician. Further, they strongly discourage using eBay or other auction sites, which do not vouch for the safety and authenticity of products sold through their services.

Other potential problems with skin care products sold online include the following.

Counterfeit products

Several reports have indicated that counterfeit skin products originating in other countries have made their way into the United States and, according to the article published on the website Fact Based Skin Care, pharmaceuticals and personal care products, including cosmetics, are among the top five types of products seized by U.S. Customs and Border Patrol agents (Coy, C. Dangers of Counterfeit Cosmetics, Aug. 4, 2014). Such products include old bottles refilled with inexpensive imitation creams or bottles made to look like legitimate products that in fact contain imitation creams. I once had a patient present with an adverse reaction to a retinol product, which she brought with her to the visit. I sent the bottle to the company, which confirmed my suspicion that the product was counterfeit – a different bottle with a similar label.

In February 2014, CBS New York ran a segment on the potential inclusion of carcinogenic and other harmful ingredients found in online personal care products touted for their low prices (CBS New York. Counterfeit Cosmetics May Be Harmful To Your Health. Feb. 27, 2014). Not even 2 weeks later, CNN reported on the arrest of two brothers in New York alleged to have masterminded a multimillion-dollar counterfeit health and beauty product ring (CNN. Zulueta A. Massive Fake Health and Beauty Supplies Ring Busted. March 9, 2014). ABC’s Good Morning America followed suit with a segment in April 2014 that exposed aspects of the use of knock-off cosmetic products (ABC News, Good Morning America. Online Beauty Bargains: Is It the Real Deal? April 3, 2014).

The Federal Bureau of Investigation has posted memos concerning counterfeit and potentially compromised and hazardous cosmetics and fragrances, offering tips aimed at readily identifying or avoiding unauthorized products.

Torie Hardee of EltaMD summarized that counterfeit products can sometimes be identified by lack of an expiration date on the bottle, discoloration or slightly different fonts on bottles and packaging, and the manufacturer’s address on the bottle.

Jan Marini Company representative Stuart Mohr noted that their company has received returns of products that they had not manufactured, as well as their own current or discontinued products returned years after the expiration date. The Jan Marini Co., and most other companies, will not guarantee any product purchased via nonauthorized resellers, because the authenticity and safety of such products cannot be verified.

“These unauthorized resellers are sophisticated, often even working in rings, and find it easy to hide their real identity,” said Mr. Mohr. “Addresses are often hidden or vague; emails are not linked to any specific person; and it’s easy to use false names. If a person is caught in an unauthorized online transaction, it’s easy to change the email address or name and start again,” he added.

©Ingram Publishing/Thinkstockphotos.com

FBI’s tips for spotting counterfeit cosmetics and fragrances

• The product is a sample size.

• The packaging differs slightly from the authentic brand (different color or font).

• The product’s wrapping appears haphazard.

• The product is being advertised as a “limited edition” even though the authentic manufacturer doesn’t offer it as a limited edition.

• The product is not listed on the manufacturer’s website.

• The price is drastically lower than the MSRP.

• The product’s consistency or texture doesn’t feel or look like the authentic brand.

• For fragrances, something seems off about the scent, and the color of the fluid in the bottle might be different than the original.

• They are being sold at nonauthorized retailers, including flea markets and discount stores.

• The label does not contain lot number, bar code, manufacturer’s address, or expiration date.

Expired products

Unscrupulous online retailers may slash prices on expired products and remove the expiration date from the package. In my practice, a patient experiencing an erythematous reaction brought in the “SkinMedica” product bottle, which looked suspicious to me. The packaging that the product was in had been discontinued 8 years earlier. It is important to remember that ingredients, particularly retinol, degrade with exposure to air, sun, and heat, and over time. This is most likely what caused my patient’s adverse reaction, and her initial savings from the product caused her several weeks of irritated skin.

Diverted products

SkinMedica reports that diverted products are a trickier issue than counterfeit products, because their packaging and formulas are sufficiently complex to make counterfeiting too difficult to be profitable. Instead, their products have been sold on the so-called gray market below the manufacturer suggested retail price (MSRP), typically online. In these cases, the company cannot help patients with returns or complaints because they cannot verify the chain of custody of the purchased product. They are addressing this problem, though, with an awareness campaign called “Authentic and Authorized.” Its goal is to alert patients and the physicians who dispense their products of the benefits of a physician-dispensed model of skin care, with best outcomes achieved when doctors are prescribing a skin care regimen. SkinMedica emphasizes that no website can guarantee outcomes comparable to a skin care professional and product quality and safety can only be enforced when dispensed through authorized channels.

Potentially illegal or toxic ingredients

Several products that have entered the United States marketed as skin lighteners, antiaging agents, and acne treatment products have been found to contain mercury, according to a consumer update from the FDA. Arsenic, lead, beryllium, and other harmful toxins as well as allergy-inducing fragrances or preservatives not approved as safe in the U.S. may also be found in such products of dubious origin.

Improper storage

Products purveyed online are often stored in hot warehouses. As mentioned above, heat degrades and alters ingredients, rendering compounds such as retinol, benzoyl peroxide, peptides, and ascorbic acid worthless. Extreme cold can also damage the chemical integrity of products. Notably, organic products are more vulnerable because they lack preservatives to gird them against temperature variations and microbes that grow in hot, damp environments.

Lookalike imposters

Generic formulations are packaged to piggyback onto the success of well-known products. Such products found in drugstores may be packaged to look like Cetaphil or Aveeno items, but cost less, and deliver less. While the ingredients on the copycats are identical to those found in the branded preparations, the order in which ingredients are added, the temperature, pH, and even when and how fast ingredients are stirred are part of the proprietary recipe of the company and play a significant role in the potential of the end product and the actions the product exerts on the skin.

Conclusion

Whether or not you sell skin care products in your office, there is much you can do to educate your patients about skin care product safety. Namely, the farther a consumer gets from the source of the product or from reliable endorsers of products, the greater the opportunity for encountering fraudulent or counterfeit products. Patients are best served by sources they can trust, such as their dermatologist. If you sell products in your office, encourage your patients to buy refills from you so they can be assured of the proper formulations. Finally, encourage your patients not to skimp when it comes to the health of their skin, reminding them that it may cost them much more in terms of time, skin irritation, improper treatment, and all related expenses to buy products cheaply from unreliable sources.

Give your patients a copy of this article so that they will understand the enormity of the problem.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

While much has been written about the Center for Medicare & Medicaid Services (CMS) plan to shift its payment system away from fee for service and toward a “value-based” structure, most physicians in small and solo private settings have given little, if any, thought to its potential impact on their practices. That is about to change.

The principal vehicle for the CMS plan is something called the Value-Based Payment Modifier (VBM), a component of the Affordable Care Act (ACA). The VBM has been off the radar of smaller private practices, because up until now it has applied only to groups with more than 10 providers. Starting this year, it applies to everyone. If you accept Medicare patients, regardless of the size of your practice, VBM will become part of your life – because your 2017 Medicare payments will be adjusted based on your 2015 VBM “score.”

That score will be based on your “quality of care” (as defined by the CMS) and how much your care costs the system, compared with care provided by other physicians. The quality component will be calculated from measures reported through the Physician Quality Reporting System (PQRS). Your practice will then be “tiered” to determine whether your performance is statistically better, the same, or worse than the national mean. The CMS has not shared all the details of its “quality tiering” formula, but you can get an idea of their general criteria by reviewing the recently released “Quality Benchmarks for the 2015 Value Modifier” at CMS.org.

To calculate the cost component, the CMS will evaluate measures that include total overall costs per beneficiary, and total costs for a composite of chronic conditions, such as (for internists) chronic obstructive pulmonary disease, heart failure, coronary artery disease, and diabetes; no one has speculated on which diseases might be used for dermatology. Practitioners are eligible for a 1% bonus if their average score is in the top 25% of all scores nationwide. You can get some sense of where you stand in the national hierarchy by studying your Quality Resource and Use Report (QRUR), which gathers information about each practice’s quality and performance rates for the VBM. Reports for the first half of 2014 were released by the CMS in April, and can be downloaded from the QRUR section of CMS.gov.

The ACA requires that the program be budget neutral – which means that all bonuses to physicians in the highest 25% must be offset by penalties – “negative adjustments” – to those in the lowest 25%. The good news is that groups with two to nine providers, and solo practitioners who report successfully for PQRS, receive only the upward or neutral adjustment for 2017, with no downward adjustments. That means you will have at least one penalty-free year to determine where you stand in the VBM pecking order – and perhaps earn a bonus.

So in summary, here is what you have to do now, in 2015, to maximize your chances of earning that upward adjustment in 2017:

• If you haven’t already, make sure your practice data are correct in the Medicare Provider Enrollment, Chain, and Ownership System (PECOS). This is where CMS will gather data for the VBM and the Physician Feedback Reports.

• Study the Quality Benchmarks and download your practice’s QRUR, as mentioned.

• Report successfully for PQRS in 2015, which will also avoid an automatic penalty of 4% in 2017.

Are there serious potential consequences inherent in this unprecedented new system? I think so. For all the talk that the transition from fee-for-service to “value-based” reimbursement would result in better care at a lower cost, there is little evidence that care is improving, and even less that costs are decreasing.

In essence, the VBM establishes arbitrary practice standards and spending ceilings. It creates new incentives to practice “cookbook” medicine, and new disincentives to order tests, consults, or medications, even when doing so would clearly be in a patient’s best interest. Physicians who have the temerity to practice medicine as they see fit, irrespective of the costs involved, will be punished.

Patients will certainly not welcome their physicians’ new reluctance to recommend appropriate interventions for fear of generating excessive costs, and should a less-than-thorough work-up lead to a missed diagnosis, the ACA offers no protection at all from any resulting malpractice litigation.

All of that said, the VBM is a reality, and can no longer be ignored if you treat Medicare patients.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters.

While much has been written about the Center for Medicare & Medicaid Services (CMS) plan to shift its payment system away from fee for service and toward a “value-based” structure, most physicians in small and solo private settings have given little, if any, thought to its potential impact on their practices. That is about to change.

The principal vehicle for the CMS plan is something called the Value-Based Payment Modifier (VBM), a component of the Affordable Care Act (ACA). The VBM has been off the radar of smaller private practices, because up until now it has applied only to groups with more than 10 providers. Starting this year, it applies to everyone. If you accept Medicare patients, regardless of the size of your practice, VBM will become part of your life – because your 2017 Medicare payments will be adjusted based on your 2015 VBM “score.”

That score will be based on your “quality of care” (as defined by the CMS) and how much your care costs the system, compared with care provided by other physicians. The quality component will be calculated from measures reported through the Physician Quality Reporting System (PQRS). Your practice will then be “tiered” to determine whether your performance is statistically better, the same, or worse than the national mean. The CMS has not shared all the details of its “quality tiering” formula, but you can get an idea of their general criteria by reviewing the recently released “Quality Benchmarks for the 2015 Value Modifier” at CMS.org.

To calculate the cost component, the CMS will evaluate measures that include total overall costs per beneficiary, and total costs for a composite of chronic conditions, such as (for internists) chronic obstructive pulmonary disease, heart failure, coronary artery disease, and diabetes; no one has speculated on which diseases might be used for dermatology. Practitioners are eligible for a 1% bonus if their average score is in the top 25% of all scores nationwide. You can get some sense of where you stand in the national hierarchy by studying your Quality Resource and Use Report (QRUR), which gathers information about each practice’s quality and performance rates for the VBM. Reports for the first half of 2014 were released by the CMS in April, and can be downloaded from the QRUR section of CMS.gov.

The ACA requires that the program be budget neutral – which means that all bonuses to physicians in the highest 25% must be offset by penalties – “negative adjustments” – to those in the lowest 25%. The good news is that groups with two to nine providers, and solo practitioners who report successfully for PQRS, receive only the upward or neutral adjustment for 2017, with no downward adjustments. That means you will have at least one penalty-free year to determine where you stand in the VBM pecking order – and perhaps earn a bonus.

So in summary, here is what you have to do now, in 2015, to maximize your chances of earning that upward adjustment in 2017:

• If you haven’t already, make sure your practice data are correct in the Medicare Provider Enrollment, Chain, and Ownership System (PECOS). This is where CMS will gather data for the VBM and the Physician Feedback Reports.

• Study the Quality Benchmarks and download your practice’s QRUR, as mentioned.

• Report successfully for PQRS in 2015, which will also avoid an automatic penalty of 4% in 2017.

Are there serious potential consequences inherent in this unprecedented new system? I think so. For all the talk that the transition from fee-for-service to “value-based” reimbursement would result in better care at a lower cost, there is little evidence that care is improving, and even less that costs are decreasing.

In essence, the VBM establishes arbitrary practice standards and spending ceilings. It creates new incentives to practice “cookbook” medicine, and new disincentives to order tests, consults, or medications, even when doing so would clearly be in a patient’s best interest. Physicians who have the temerity to practice medicine as they see fit, irrespective of the costs involved, will be punished.

Patients will certainly not welcome their physicians’ new reluctance to recommend appropriate interventions for fear of generating excessive costs, and should a less-than-thorough work-up lead to a missed diagnosis, the ACA offers no protection at all from any resulting malpractice litigation.

All of that said, the VBM is a reality, and can no longer be ignored if you treat Medicare patients.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters.

While much has been written about the Center for Medicare & Medicaid Services (CMS) plan to shift its payment system away from fee for service and toward a “value-based” structure, most physicians in small and solo private settings have given little, if any, thought to its potential impact on their practices. That is about to change.

The principal vehicle for the CMS plan is something called the Value-Based Payment Modifier (VBM), a component of the Affordable Care Act (ACA). The VBM has been off the radar of smaller private practices, because up until now it has applied only to groups with more than 10 providers. Starting this year, it applies to everyone. If you accept Medicare patients, regardless of the size of your practice, VBM will become part of your life – because your 2017 Medicare payments will be adjusted based on your 2015 VBM “score.”

That score will be based on your “quality of care” (as defined by the CMS) and how much your care costs the system, compared with care provided by other physicians. The quality component will be calculated from measures reported through the Physician Quality Reporting System (PQRS). Your practice will then be “tiered” to determine whether your performance is statistically better, the same, or worse than the national mean. The CMS has not shared all the details of its “quality tiering” formula, but you can get an idea of their general criteria by reviewing the recently released “Quality Benchmarks for the 2015 Value Modifier” at CMS.org.

To calculate the cost component, the CMS will evaluate measures that include total overall costs per beneficiary, and total costs for a composite of chronic conditions, such as (for internists) chronic obstructive pulmonary disease, heart failure, coronary artery disease, and diabetes; no one has speculated on which diseases might be used for dermatology. Practitioners are eligible for a 1% bonus if their average score is in the top 25% of all scores nationwide. You can get some sense of where you stand in the national hierarchy by studying your Quality Resource and Use Report (QRUR), which gathers information about each practice’s quality and performance rates for the VBM. Reports for the first half of 2014 were released by the CMS in April, and can be downloaded from the QRUR section of CMS.gov.

The ACA requires that the program be budget neutral – which means that all bonuses to physicians in the highest 25% must be offset by penalties – “negative adjustments” – to those in the lowest 25%. The good news is that groups with two to nine providers, and solo practitioners who report successfully for PQRS, receive only the upward or neutral adjustment for 2017, with no downward adjustments. That means you will have at least one penalty-free year to determine where you stand in the VBM pecking order – and perhaps earn a bonus.

So in summary, here is what you have to do now, in 2015, to maximize your chances of earning that upward adjustment in 2017:

• If you haven’t already, make sure your practice data are correct in the Medicare Provider Enrollment, Chain, and Ownership System (PECOS). This is where CMS will gather data for the VBM and the Physician Feedback Reports.

• Study the Quality Benchmarks and download your practice’s QRUR, as mentioned.

• Report successfully for PQRS in 2015, which will also avoid an automatic penalty of 4% in 2017.

Are there serious potential consequences inherent in this unprecedented new system? I think so. For all the talk that the transition from fee-for-service to “value-based” reimbursement would result in better care at a lower cost, there is little evidence that care is improving, and even less that costs are decreasing.

In essence, the VBM establishes arbitrary practice standards and spending ceilings. It creates new incentives to practice “cookbook” medicine, and new disincentives to order tests, consults, or medications, even when doing so would clearly be in a patient’s best interest. Physicians who have the temerity to practice medicine as they see fit, irrespective of the costs involved, will be punished.

Patients will certainly not welcome their physicians’ new reluctance to recommend appropriate interventions for fear of generating excessive costs, and should a less-than-thorough work-up lead to a missed diagnosis, the ACA offers no protection at all from any resulting malpractice litigation.

All of that said, the VBM is a reality, and can no longer be ignored if you treat Medicare patients.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters.