I have been a traveling road show for the last 2 years, explaining the value of dermatology to insurers. It is amazing how poorly understood we are by payers.

Let me give you an example. Currently, dermatologists treat about 70% of all skin cancers. This is up from the 10% we treated 30 years ago, but if you think about it, it should be 98% or 99%. There were 5.4 million skin cancers in the United States in 2012. The great majority were nonmelanoma skin cancers (at an interesting ratio of 1:1 for basal cell carcinoma and squamous cell carcinoma), and only about 75,000 were melanomas. About 80% of all melanomas are less than 1 mm in thickness and undoubtedly appropriate for local excision in the office. Dermatologists treat these skin cancers at less than ¹/₅ the cost of treatment in a facility. We, and a few primary care physicians, are the only physicians who are not operating room dependent. We can remove these cancers under local anesthesia in the office, without an anesthesiologist, multiple nurses, intravenous lines, preop labs, and the other high fixed costs associated with a hospital procedure, and we can do it promptly. Insurers should be pounding their drums to demand that the vast majority of skin cancers be treated in the office setting, rather than in a hospital. Maybe all skin cancer patients should be required to get “precertified” by a dermatologist before they are sent to a hospital for a procedure. This would improve quality and greatly cut costs.

Insurers always drop their jaws when I explain this to them. They have never matched up the costs of the physicians and the costs of the facilities where procedures are performed. They need to consider the value of the dermatologist in providing an accurate, quick diagnosis, with immediate exclusion of benign lesions and elimination of the long wait times to get a cancer removed. It costs less to get a skin cancer diagnosed and removed by a dermatologist than to get a new set of car tires installed, and we can often do it in about the same amount of time. Compare that with $150,000 spent annually to treat metastatic melanoma.

In addition, fewer dermatologists mean longer wait times to see the dermatologist, causing what I call the “spillover” effect. When patients cannot get in to see the dermatologist, they call their primary care physician, who sends them down to the hospital to see their general surgeon on lumps and bumps day. Everything gets removed, benign or not, in the hospital outpatient department.

That is why it is insane for insurers to be eliminating dermatologists wholesale from their “tight” networks. Their software tells them they will save money in the short term, but they won’t because of the spillover, and it is very foolish in the long term. With the advent of the Affordable Care Act, patients cannot be excluded for preexisting conditions, and these patients all become long-term clients of one insurer or another. What is neglected today becomes a nightmare tomorrow. Dermatology offers an extraordinarily high value quotient, but only if insurers have enough sense to let the patients see us.

Dr. Coldiron is in private practice, but maintains a clinical assistant professorship of dermatology at the University of Cincinnati. Email him at [email protected].

I have been a traveling road show for the last 2 years, explaining the value of dermatology to insurers. It is amazing how poorly understood we are by payers.

Let me give you an example. Currently, dermatologists treat about 70% of all skin cancers. This is up from the 10% we treated 30 years ago, but if you think about it, it should be 98% or 99%. There were 5.4 million skin cancers in the United States in 2012. The great majority were nonmelanoma skin cancers (at an interesting ratio of 1:1 for basal cell carcinoma and squamous cell carcinoma), and only about 75,000 were melanomas. About 80% of all melanomas are less than 1 mm in thickness and undoubtedly appropriate for local excision in the office. Dermatologists treat these skin cancers at less than ¹/₅ the cost of treatment in a facility. We, and a few primary care physicians, are the only physicians who are not operating room dependent. We can remove these cancers under local anesthesia in the office, without an anesthesiologist, multiple nurses, intravenous lines, preop labs, and the other high fixed costs associated with a hospital procedure, and we can do it promptly. Insurers should be pounding their drums to demand that the vast majority of skin cancers be treated in the office setting, rather than in a hospital. Maybe all skin cancer patients should be required to get “precertified” by a dermatologist before they are sent to a hospital for a procedure. This would improve quality and greatly cut costs.

Insurers always drop their jaws when I explain this to them. They have never matched up the costs of the physicians and the costs of the facilities where procedures are performed. They need to consider the value of the dermatologist in providing an accurate, quick diagnosis, with immediate exclusion of benign lesions and elimination of the long wait times to get a cancer removed. It costs less to get a skin cancer diagnosed and removed by a dermatologist than to get a new set of car tires installed, and we can often do it in about the same amount of time. Compare that with $150,000 spent annually to treat metastatic melanoma.

In addition, fewer dermatologists mean longer wait times to see the dermatologist, causing what I call the “spillover” effect. When patients cannot get in to see the dermatologist, they call their primary care physician, who sends them down to the hospital to see their general surgeon on lumps and bumps day. Everything gets removed, benign or not, in the hospital outpatient department.

That is why it is insane for insurers to be eliminating dermatologists wholesale from their “tight” networks. Their software tells them they will save money in the short term, but they won’t because of the spillover, and it is very foolish in the long term. With the advent of the Affordable Care Act, patients cannot be excluded for preexisting conditions, and these patients all become long-term clients of one insurer or another. What is neglected today becomes a nightmare tomorrow. Dermatology offers an extraordinarily high value quotient, but only if insurers have enough sense to let the patients see us.

Dr. Coldiron is in private practice, but maintains a clinical assistant professorship of dermatology at the University of Cincinnati. Email him at [email protected].

I have been a traveling road show for the last 2 years, explaining the value of dermatology to insurers. It is amazing how poorly understood we are by payers.

Let me give you an example. Currently, dermatologists treat about 70% of all skin cancers. This is up from the 10% we treated 30 years ago, but if you think about it, it should be 98% or 99%. There were 5.4 million skin cancers in the United States in 2012. The great majority were nonmelanoma skin cancers (at an interesting ratio of 1:1 for basal cell carcinoma and squamous cell carcinoma), and only about 75,000 were melanomas. About 80% of all melanomas are less than 1 mm in thickness and undoubtedly appropriate for local excision in the office. Dermatologists treat these skin cancers at less than ¹/₅ the cost of treatment in a facility. We, and a few primary care physicians, are the only physicians who are not operating room dependent. We can remove these cancers under local anesthesia in the office, without an anesthesiologist, multiple nurses, intravenous lines, preop labs, and the other high fixed costs associated with a hospital procedure, and we can do it promptly. Insurers should be pounding their drums to demand that the vast majority of skin cancers be treated in the office setting, rather than in a hospital. Maybe all skin cancer patients should be required to get “precertified” by a dermatologist before they are sent to a hospital for a procedure. This would improve quality and greatly cut costs.

Insurers always drop their jaws when I explain this to them. They have never matched up the costs of the physicians and the costs of the facilities where procedures are performed. They need to consider the value of the dermatologist in providing an accurate, quick diagnosis, with immediate exclusion of benign lesions and elimination of the long wait times to get a cancer removed. It costs less to get a skin cancer diagnosed and removed by a dermatologist than to get a new set of car tires installed, and we can often do it in about the same amount of time. Compare that with $150,000 spent annually to treat metastatic melanoma.

In addition, fewer dermatologists mean longer wait times to see the dermatologist, causing what I call the “spillover” effect. When patients cannot get in to see the dermatologist, they call their primary care physician, who sends them down to the hospital to see their general surgeon on lumps and bumps day. Everything gets removed, benign or not, in the hospital outpatient department.

That is why it is insane for insurers to be eliminating dermatologists wholesale from their “tight” networks. Their software tells them they will save money in the short term, but they won’t because of the spillover, and it is very foolish in the long term. With the advent of the Affordable Care Act, patients cannot be excluded for preexisting conditions, and these patients all become long-term clients of one insurer or another. What is neglected today becomes a nightmare tomorrow. Dermatology offers an extraordinarily high value quotient, but only if insurers have enough sense to let the patients see us.

Dr. Coldiron is in private practice, but maintains a clinical assistant professorship of dermatology at the University of Cincinnati. Email him at [email protected].

Prescription medications

Photo courtesy of the CDC

Patients admitted to the emergency department (ED) for venous thromboembolism (VTE) can be placed on oral anticoagulation and discharged immediately, according to research published in Academic Emergency Medicine.

The study showed that patients who received anticoagulation with rivaroxaban, were discharged from the ED right away, and did not undergo weekly monitoring had a low rate of VTE recurrence and major or clinically relevant bleeding.

A related study suggested this approach was less costly than standard treatment with heparin and warfarin.

The prospect of being able to send patients home from the ED on the day of admission is a quality of life issue, according to Jeffrey A. Kline, MD, a professor at the Indiana University School of Medicine in Indianapolis and an author of both studies.

“We really do empower the patient more with [rivaroxaban],” he said. “Patients say treatment with no injections is a much better option. [Rivaroxaban] takes a condition that is life-threatening and makes it something the patient can control.”

Safety and efficacy

For the first study, Dr Kline and his colleagues evaluated 106 low-risk patients who were diagnosed with deep vein thrombosis (DVT) or pulmonary embolism (PE) at 2 metropolitan EDs.

The patients were admitted between March 2013 and April 2014. Seventy-one patients had DVT, 30 had PE, and 5 had both.

The standard of care for these patients is heparin injections, followed by oral warfarin and close monitoring to ensure safe dosage levels.

But patients in this study received rivaroxaban, which does not require blood monitoring, and were released from the hospital on the day of admission. The patients did undergo follow up-monitoring at 2 weeks, 5 weeks, 3 months, and 6 months.

The researchers followed patients for a mean of 389 days (range, 213 to 594 days). None of the patients had a VTE recurrence, major bleeding, or clinically relevant bleeding while on therapy.

However, 3 patients (2.8%) experienced DVT recurrence within a year of stopping treatment. All 3 had completed their prescribed treatment.

“This study is about giving patients a new option,” Dr Kline said. “Treating patients at home for blood clots was found to have fewer errors than the standard of care and better outcomes. Patients [receiving standard therapy] have to be taught to give themselves injections, and it scares them to death. Almost everyone has taken a pill, so there is no learning curve for patients [with rivaroxaban].”

Treatment costs

In the second study, Dr Kline and his colleagues compared costs associated with standard treatment and rivaroxaban. Total hospital charges with the rivaroxaban protocol were about half the cost of charges for standard therapy.

The researchers evaluated 97 patients, matching them for age, sex, and the severity of their illness. At 6 months after ED admission, the median cost was $4787 (interquartile range=$3042 to $7596) for the rivaroxaban group and $11,128 (interquartile range=$8110 to $23,390) for the group treated with standard care (P<0.001).

Among patients with PE, costs were 57% lower in the rivaroxaban group than the standard therapy group (P<0.001). For patients with DVT, costs were 56% lower in the rivaroxaban group (P=0.003).

Prescription medications

Photo courtesy of the CDC

Patients admitted to the emergency department (ED) for venous thromboembolism (VTE) can be placed on oral anticoagulation and discharged immediately, according to research published in Academic Emergency Medicine.

The study showed that patients who received anticoagulation with rivaroxaban, were discharged from the ED right away, and did not undergo weekly monitoring had a low rate of VTE recurrence and major or clinically relevant bleeding.

A related study suggested this approach was less costly than standard treatment with heparin and warfarin.

The prospect of being able to send patients home from the ED on the day of admission is a quality of life issue, according to Jeffrey A. Kline, MD, a professor at the Indiana University School of Medicine in Indianapolis and an author of both studies.

“We really do empower the patient more with [rivaroxaban],” he said. “Patients say treatment with no injections is a much better option. [Rivaroxaban] takes a condition that is life-threatening and makes it something the patient can control.”

Safety and efficacy

For the first study, Dr Kline and his colleagues evaluated 106 low-risk patients who were diagnosed with deep vein thrombosis (DVT) or pulmonary embolism (PE) at 2 metropolitan EDs.

The patients were admitted between March 2013 and April 2014. Seventy-one patients had DVT, 30 had PE, and 5 had both.

The standard of care for these patients is heparin injections, followed by oral warfarin and close monitoring to ensure safe dosage levels.

But patients in this study received rivaroxaban, which does not require blood monitoring, and were released from the hospital on the day of admission. The patients did undergo follow up-monitoring at 2 weeks, 5 weeks, 3 months, and 6 months.

The researchers followed patients for a mean of 389 days (range, 213 to 594 days). None of the patients had a VTE recurrence, major bleeding, or clinically relevant bleeding while on therapy.

However, 3 patients (2.8%) experienced DVT recurrence within a year of stopping treatment. All 3 had completed their prescribed treatment.

“This study is about giving patients a new option,” Dr Kline said. “Treating patients at home for blood clots was found to have fewer errors than the standard of care and better outcomes. Patients [receiving standard therapy] have to be taught to give themselves injections, and it scares them to death. Almost everyone has taken a pill, so there is no learning curve for patients [with rivaroxaban].”

Treatment costs

In the second study, Dr Kline and his colleagues compared costs associated with standard treatment and rivaroxaban. Total hospital charges with the rivaroxaban protocol were about half the cost of charges for standard therapy.

The researchers evaluated 97 patients, matching them for age, sex, and the severity of their illness. At 6 months after ED admission, the median cost was $4787 (interquartile range=$3042 to $7596) for the rivaroxaban group and $11,128 (interquartile range=$8110 to $23,390) for the group treated with standard care (P<0.001).

Among patients with PE, costs were 57% lower in the rivaroxaban group than the standard therapy group (P<0.001). For patients with DVT, costs were 56% lower in the rivaroxaban group (P=0.003).

Prescription medications

Photo courtesy of the CDC

Patients admitted to the emergency department (ED) for venous thromboembolism (VTE) can be placed on oral anticoagulation and discharged immediately, according to research published in Academic Emergency Medicine.

The study showed that patients who received anticoagulation with rivaroxaban, were discharged from the ED right away, and did not undergo weekly monitoring had a low rate of VTE recurrence and major or clinically relevant bleeding.

A related study suggested this approach was less costly than standard treatment with heparin and warfarin.

The prospect of being able to send patients home from the ED on the day of admission is a quality of life issue, according to Jeffrey A. Kline, MD, a professor at the Indiana University School of Medicine in Indianapolis and an author of both studies.

“We really do empower the patient more with [rivaroxaban],” he said. “Patients say treatment with no injections is a much better option. [Rivaroxaban] takes a condition that is life-threatening and makes it something the patient can control.”

Safety and efficacy

For the first study, Dr Kline and his colleagues evaluated 106 low-risk patients who were diagnosed with deep vein thrombosis (DVT) or pulmonary embolism (PE) at 2 metropolitan EDs.

The patients were admitted between March 2013 and April 2014. Seventy-one patients had DVT, 30 had PE, and 5 had both.

The standard of care for these patients is heparin injections, followed by oral warfarin and close monitoring to ensure safe dosage levels.

But patients in this study received rivaroxaban, which does not require blood monitoring, and were released from the hospital on the day of admission. The patients did undergo follow up-monitoring at 2 weeks, 5 weeks, 3 months, and 6 months.

The researchers followed patients for a mean of 389 days (range, 213 to 594 days). None of the patients had a VTE recurrence, major bleeding, or clinically relevant bleeding while on therapy.

However, 3 patients (2.8%) experienced DVT recurrence within a year of stopping treatment. All 3 had completed their prescribed treatment.

“This study is about giving patients a new option,” Dr Kline said. “Treating patients at home for blood clots was found to have fewer errors than the standard of care and better outcomes. Patients [receiving standard therapy] have to be taught to give themselves injections, and it scares them to death. Almost everyone has taken a pill, so there is no learning curve for patients [with rivaroxaban].”

Treatment costs

In the second study, Dr Kline and his colleagues compared costs associated with standard treatment and rivaroxaban. Total hospital charges with the rivaroxaban protocol were about half the cost of charges for standard therapy.

The researchers evaluated 97 patients, matching them for age, sex, and the severity of their illness. At 6 months after ED admission, the median cost was $4787 (interquartile range=$3042 to $7596) for the rivaroxaban group and $11,128 (interquartile range=$8110 to $23,390) for the group treated with standard care (P<0.001).

Among patients with PE, costs were 57% lower in the rivaroxaban group than the standard therapy group (P<0.001). For patients with DVT, costs were 56% lower in the rivaroxaban group (P=0.003).

Patient receiving chemotherapy

Photo by Rhoda Baer

New research suggests the polyphenols resveratrol and quercetin could be used to augment treatment with the anthracycline doxorubicin.

Investigators found they could increase the bioavailability of resveratrol and quercetin using copolymers that make the compounds water soluble and allow for their injection into the blood stream.

The team then showed the compounds synergize with doxorubicin while also reducing cardiac toxicity.

Although doxorubicin has proven effective against lymphomas, leukemias, and other cancers, the drug can only be used for a limited time because it confers cardiotoxicity.

The co-administration of resveratrol and quercetin might allow for much more extensive use of doxorubicin, while at the same time improving its efficacy and demonstrating the polyphenols’ own anticancer properties, investigators said.

They described research supporting this idea in the Journal of Controlled Release.

“This has great potential to improve chemotherapeutic cancer treatment,” said Adam Alani, PhD, of Oregon State University in Portland.

“The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of [doxorubicin]. And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug.”

Dr Alani said further research may demonstrate that these compounds can completely eliminate the cardiotoxicity of doxorubicin, as they scavenge the toxic free radicals produced by this drug.

It’s also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves or in combination with a wider range of other chemotherapeutic drugs.

Increasing bioavailability

Resveratrol is a natural compound found in foods such as grapes, red wine, green tea, berries, and dark chocolate. Quercetin reaches some of its highest natural levels in capers, some berries, and leafy greens.

When consumed via food or taken as supplements, these polyphenol compounds reach only a tiny fraction of the level that’s possible with direct injection. Such injection was not possible until Dr Alani and his colleagues adapted the use of polymeric micelles.

Specifically, the investigators combined resveratrol and quercetin in Pluronic F127 micelles (mRQ). Pluronics are triblock copolymers consisting of a polypropylene oxide chain flanked with 2 polyethylene oxide chains that can self-assemble into polymeric micelles. The micelles have hydrophobic cores that help solubilize compounds with poor aqueous solubility.

“There are several advantages with this system,” Dr Alani said. “We can finally reach clinical levels of these polyphenols in the body. We can load both the compounds at one time to help control the cardiotoxicity of the cancer drug, and we can help the polyphenols accumulate in cancer cells where they have their own anticancer properties.”

In combination with doxorubicin

The investigators prepared mRQ micelles that were capable of retaining 1.1 mg/mL of resveratrol and 1.42 mg/mL of quercetin. They then tested mRQ in combination with doxorubicin in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2).

The team found that a resveratrol-quercetin-doxorubicin ratio of 10:10:1 was synergistic in SKOV-3 cells and antagonistic in H9C2 cells.

mRQ did not interfere with doxorubicin’s caspase activity in SKOV-3 cells but significantly decreased the activity in H9C2 cells. Likewise, there were no changes in the generation of reactive oxygen species in SKOV-3 cells, but there was significant scavenging in H9C2 cells.

The investigators also administered doxorubicin, with or without mRQ, to healthy mice and found that mRQ “conferred full cardioprotection.”

Dr Alani noted that previous research suggested resveratrol and quercetin are safe when given at high concentrations, but additional research is needed.

Patient receiving chemotherapy

Photo by Rhoda Baer

New research suggests the polyphenols resveratrol and quercetin could be used to augment treatment with the anthracycline doxorubicin.

Investigators found they could increase the bioavailability of resveratrol and quercetin using copolymers that make the compounds water soluble and allow for their injection into the blood stream.

The team then showed the compounds synergize with doxorubicin while also reducing cardiac toxicity.

Although doxorubicin has proven effective against lymphomas, leukemias, and other cancers, the drug can only be used for a limited time because it confers cardiotoxicity.

The co-administration of resveratrol and quercetin might allow for much more extensive use of doxorubicin, while at the same time improving its efficacy and demonstrating the polyphenols’ own anticancer properties, investigators said.

They described research supporting this idea in the Journal of Controlled Release.

“This has great potential to improve chemotherapeutic cancer treatment,” said Adam Alani, PhD, of Oregon State University in Portland.

“The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of [doxorubicin]. And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug.”

Dr Alani said further research may demonstrate that these compounds can completely eliminate the cardiotoxicity of doxorubicin, as they scavenge the toxic free radicals produced by this drug.

It’s also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves or in combination with a wider range of other chemotherapeutic drugs.

Increasing bioavailability

Resveratrol is a natural compound found in foods such as grapes, red wine, green tea, berries, and dark chocolate. Quercetin reaches some of its highest natural levels in capers, some berries, and leafy greens.

When consumed via food or taken as supplements, these polyphenol compounds reach only a tiny fraction of the level that’s possible with direct injection. Such injection was not possible until Dr Alani and his colleagues adapted the use of polymeric micelles.

Specifically, the investigators combined resveratrol and quercetin in Pluronic F127 micelles (mRQ). Pluronics are triblock copolymers consisting of a polypropylene oxide chain flanked with 2 polyethylene oxide chains that can self-assemble into polymeric micelles. The micelles have hydrophobic cores that help solubilize compounds with poor aqueous solubility.

“There are several advantages with this system,” Dr Alani said. “We can finally reach clinical levels of these polyphenols in the body. We can load both the compounds at one time to help control the cardiotoxicity of the cancer drug, and we can help the polyphenols accumulate in cancer cells where they have their own anticancer properties.”

In combination with doxorubicin

The investigators prepared mRQ micelles that were capable of retaining 1.1 mg/mL of resveratrol and 1.42 mg/mL of quercetin. They then tested mRQ in combination with doxorubicin in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2).

The team found that a resveratrol-quercetin-doxorubicin ratio of 10:10:1 was synergistic in SKOV-3 cells and antagonistic in H9C2 cells.

mRQ did not interfere with doxorubicin’s caspase activity in SKOV-3 cells but significantly decreased the activity in H9C2 cells. Likewise, there were no changes in the generation of reactive oxygen species in SKOV-3 cells, but there was significant scavenging in H9C2 cells.

The investigators also administered doxorubicin, with or without mRQ, to healthy mice and found that mRQ “conferred full cardioprotection.”

Dr Alani noted that previous research suggested resveratrol and quercetin are safe when given at high concentrations, but additional research is needed.

Patient receiving chemotherapy

Photo by Rhoda Baer

New research suggests the polyphenols resveratrol and quercetin could be used to augment treatment with the anthracycline doxorubicin.

Investigators found they could increase the bioavailability of resveratrol and quercetin using copolymers that make the compounds water soluble and allow for their injection into the blood stream.

The team then showed the compounds synergize with doxorubicin while also reducing cardiac toxicity.

Although doxorubicin has proven effective against lymphomas, leukemias, and other cancers, the drug can only be used for a limited time because it confers cardiotoxicity.

The co-administration of resveratrol and quercetin might allow for much more extensive use of doxorubicin, while at the same time improving its efficacy and demonstrating the polyphenols’ own anticancer properties, investigators said.

They described research supporting this idea in the Journal of Controlled Release.

“This has great potential to improve chemotherapeutic cancer treatment,” said Adam Alani, PhD, of Oregon State University in Portland.

“The co-administration of high levels of resveratrol and quercetin, in both in vitro and in vivo studies, shows that it significantly reduces the cardiac toxicity of [doxorubicin]. And these compounds have a synergistic effect that enhances the efficacy of the cancer drug, by sensitizing the cancer cells to the effects of the drug.”

Dr Alani said further research may demonstrate that these compounds can completely eliminate the cardiotoxicity of doxorubicin, as they scavenge the toxic free radicals produced by this drug.

It’s also possible, he said, that administration of these natural polyphenols could have value in cancer therapy by themselves or in combination with a wider range of other chemotherapeutic drugs.

Increasing bioavailability

Resveratrol is a natural compound found in foods such as grapes, red wine, green tea, berries, and dark chocolate. Quercetin reaches some of its highest natural levels in capers, some berries, and leafy greens.

When consumed via food or taken as supplements, these polyphenol compounds reach only a tiny fraction of the level that’s possible with direct injection. Such injection was not possible until Dr Alani and his colleagues adapted the use of polymeric micelles.

Specifically, the investigators combined resveratrol and quercetin in Pluronic F127 micelles (mRQ). Pluronics are triblock copolymers consisting of a polypropylene oxide chain flanked with 2 polyethylene oxide chains that can self-assemble into polymeric micelles. The micelles have hydrophobic cores that help solubilize compounds with poor aqueous solubility.

“There are several advantages with this system,” Dr Alani said. “We can finally reach clinical levels of these polyphenols in the body. We can load both the compounds at one time to help control the cardiotoxicity of the cancer drug, and we can help the polyphenols accumulate in cancer cells where they have their own anticancer properties.”

In combination with doxorubicin

The investigators prepared mRQ micelles that were capable of retaining 1.1 mg/mL of resveratrol and 1.42 mg/mL of quercetin. They then tested mRQ in combination with doxorubicin in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2).

The team found that a resveratrol-quercetin-doxorubicin ratio of 10:10:1 was synergistic in SKOV-3 cells and antagonistic in H9C2 cells.

mRQ did not interfere with doxorubicin’s caspase activity in SKOV-3 cells but significantly decreased the activity in H9C2 cells. Likewise, there were no changes in the generation of reactive oxygen species in SKOV-3 cells, but there was significant scavenging in H9C2 cells.

The investigators also administered doxorubicin, with or without mRQ, to healthy mice and found that mRQ “conferred full cardioprotection.”

Dr Alani noted that previous research suggested resveratrol and quercetin are safe when given at high concentrations, but additional research is needed.

Thalassemia major

Low bioavailability of the amino acid arginine may contribute to cardiopulmonary dysfunction in patients with β-thalassemia, according to researchers.

Via previous work, the team found that arginine deficiency is a major factor in acute pain episodes in sickle cell disease.

With the current study, they discovered that arginase activity and concentration correlate with echocardiographic and cardiac-MRI measurements of cardiopulmonary function.

Claudia R. Morris, MD, of Emory University School of Medicine in Atlanta, Georgia, and her colleagues described this research in the British Journal of Haematology.

“We are finding that arginine dysregulation is an important hematologic mechanism beyond sickle cell disease,” Dr Morris said. “This new study shows that it plays a role in thalassemia patients as well and may contribute to cardiopulmonary dysfunction. Interventions aimed at restoring arginine bioavailability could be a promising area of focus for new therapeutics.”

Dr Morris and her colleagues noted that pulmonary hypertension (PH) is a common problem in patients with thalassemia. An elevated tricuspid-regurgitant jet-velocity (TRV) of 2.5 m/s or greater on Doppler echocardiography can identify patients with an increased risk of PH. But a right heart catheterization is required to confirm the condition.

The researchers wanted to provide a comprehensive description of the cardiopulmonary and biological profile of thalassemia patients at risk of developing PH. So they analyzed 27 patients with β-thalassemia.

Fourteen patients had an elevated TRV (≥ 2.5 m/s). According to echocardiography, these patients had a significantly larger right atrial size (P=0.03), left atrial size (P=0.002), left ventricular (LV) mass (P=0.03), and left septal-wall thickness (P=0.03) than patients with a TRV below 2.5 m/s.

According to MRI, patients with elevated TRV had significantly higher left atrial volume than patients with a TRV < 2.5 m/s (P=0.008).

Patients with an elevated TRV also had elevated lactate dehydrogenase (LDH) levels (P=0.03) and biomarkers of abnormal coagulation, including thrombin-antithrombin complex (P=0.04) and monoclonal prothrombin fragment 1.2 (P=0.02).

Patients with a TRV ≥ 2.5 m/s had significantly lower plasma arginine concentration (P<0.001) and biomarkers of global arginine bioavailability, including plasma arginine/ornithine ratio (P=0.01) and mean plasma global arginine bioavailability ratio (arginine/ornithine + citrulline ratio, P=0.04).

These patients also had significantly higher arginase concentration and activity than patients with TRV below 2.5 m/s (P=0.02).

These findings prompted the researchers to evaluate the relationship between arginase activity/concentration and clinical and laboratory markers of disease severity.

They found that arginase concentration was significantly correlated with several parameters of cardiovascular function, including left atrial volume (echo and MRI), right atrial volume (MRI), LV end systolic volume (echo and MRI), LV end diastolic volume (echo and MRI), LV mass (echo and MRI), and cardiac index (echo).

Arginase concentration was also significantly correlated with white blood cell count (P=0.03), plasma arginine (P=0.0002), arginine/ornithine (P=0.01) and arginine/ornithine + citrulline ratios (P=0.05), and hemoglobin (P=0.02), bilirubin (P=0.02), and LDH levels (P=0.001).

In multiple regression analysis, only cardiac index, bilirubin, and plasma arginine/ornithine ratio remained significantly associated with arginase concentration (P<0.05 for all).

Arginase activity was significantly correlated with several biomarkers of coagulation, including monoclonal prothrombin fragment 1.2 (P=0.04), thrombin-antithrombin complex (P=0.04), and tissue factor concentration (P=0.02).

Considering these results together, the researchers said it seems low arginine bioavailability contributes to cardiopulmonary dysfunction in patients with β-thalassemia.

Thalassemia major

Low bioavailability of the amino acid arginine may contribute to cardiopulmonary dysfunction in patients with β-thalassemia, according to researchers.

Via previous work, the team found that arginine deficiency is a major factor in acute pain episodes in sickle cell disease.

With the current study, they discovered that arginase activity and concentration correlate with echocardiographic and cardiac-MRI measurements of cardiopulmonary function.

Claudia R. Morris, MD, of Emory University School of Medicine in Atlanta, Georgia, and her colleagues described this research in the British Journal of Haematology.

“We are finding that arginine dysregulation is an important hematologic mechanism beyond sickle cell disease,” Dr Morris said. “This new study shows that it plays a role in thalassemia patients as well and may contribute to cardiopulmonary dysfunction. Interventions aimed at restoring arginine bioavailability could be a promising area of focus for new therapeutics.”

Dr Morris and her colleagues noted that pulmonary hypertension (PH) is a common problem in patients with thalassemia. An elevated tricuspid-regurgitant jet-velocity (TRV) of 2.5 m/s or greater on Doppler echocardiography can identify patients with an increased risk of PH. But a right heart catheterization is required to confirm the condition.

The researchers wanted to provide a comprehensive description of the cardiopulmonary and biological profile of thalassemia patients at risk of developing PH. So they analyzed 27 patients with β-thalassemia.

Fourteen patients had an elevated TRV (≥ 2.5 m/s). According to echocardiography, these patients had a significantly larger right atrial size (P=0.03), left atrial size (P=0.002), left ventricular (LV) mass (P=0.03), and left septal-wall thickness (P=0.03) than patients with a TRV below 2.5 m/s.

According to MRI, patients with elevated TRV had significantly higher left atrial volume than patients with a TRV < 2.5 m/s (P=0.008).

Patients with an elevated TRV also had elevated lactate dehydrogenase (LDH) levels (P=0.03) and biomarkers of abnormal coagulation, including thrombin-antithrombin complex (P=0.04) and monoclonal prothrombin fragment 1.2 (P=0.02).

Patients with a TRV ≥ 2.5 m/s had significantly lower plasma arginine concentration (P<0.001) and biomarkers of global arginine bioavailability, including plasma arginine/ornithine ratio (P=0.01) and mean plasma global arginine bioavailability ratio (arginine/ornithine + citrulline ratio, P=0.04).

These patients also had significantly higher arginase concentration and activity than patients with TRV below 2.5 m/s (P=0.02).

These findings prompted the researchers to evaluate the relationship between arginase activity/concentration and clinical and laboratory markers of disease severity.

They found that arginase concentration was significantly correlated with several parameters of cardiovascular function, including left atrial volume (echo and MRI), right atrial volume (MRI), LV end systolic volume (echo and MRI), LV end diastolic volume (echo and MRI), LV mass (echo and MRI), and cardiac index (echo).

Arginase concentration was also significantly correlated with white blood cell count (P=0.03), plasma arginine (P=0.0002), arginine/ornithine (P=0.01) and arginine/ornithine + citrulline ratios (P=0.05), and hemoglobin (P=0.02), bilirubin (P=0.02), and LDH levels (P=0.001).

In multiple regression analysis, only cardiac index, bilirubin, and plasma arginine/ornithine ratio remained significantly associated with arginase concentration (P<0.05 for all).

Arginase activity was significantly correlated with several biomarkers of coagulation, including monoclonal prothrombin fragment 1.2 (P=0.04), thrombin-antithrombin complex (P=0.04), and tissue factor concentration (P=0.02).

Considering these results together, the researchers said it seems low arginine bioavailability contributes to cardiopulmonary dysfunction in patients with β-thalassemia.

Thalassemia major

Low bioavailability of the amino acid arginine may contribute to cardiopulmonary dysfunction in patients with β-thalassemia, according to researchers.

Via previous work, the team found that arginine deficiency is a major factor in acute pain episodes in sickle cell disease.

With the current study, they discovered that arginase activity and concentration correlate with echocardiographic and cardiac-MRI measurements of cardiopulmonary function.

Claudia R. Morris, MD, of Emory University School of Medicine in Atlanta, Georgia, and her colleagues described this research in the British Journal of Haematology.

“We are finding that arginine dysregulation is an important hematologic mechanism beyond sickle cell disease,” Dr Morris said. “This new study shows that it plays a role in thalassemia patients as well and may contribute to cardiopulmonary dysfunction. Interventions aimed at restoring arginine bioavailability could be a promising area of focus for new therapeutics.”

Dr Morris and her colleagues noted that pulmonary hypertension (PH) is a common problem in patients with thalassemia. An elevated tricuspid-regurgitant jet-velocity (TRV) of 2.5 m/s or greater on Doppler echocardiography can identify patients with an increased risk of PH. But a right heart catheterization is required to confirm the condition.

The researchers wanted to provide a comprehensive description of the cardiopulmonary and biological profile of thalassemia patients at risk of developing PH. So they analyzed 27 patients with β-thalassemia.

Fourteen patients had an elevated TRV (≥ 2.5 m/s). According to echocardiography, these patients had a significantly larger right atrial size (P=0.03), left atrial size (P=0.002), left ventricular (LV) mass (P=0.03), and left septal-wall thickness (P=0.03) than patients with a TRV below 2.5 m/s.

According to MRI, patients with elevated TRV had significantly higher left atrial volume than patients with a TRV < 2.5 m/s (P=0.008).

Patients with an elevated TRV also had elevated lactate dehydrogenase (LDH) levels (P=0.03) and biomarkers of abnormal coagulation, including thrombin-antithrombin complex (P=0.04) and monoclonal prothrombin fragment 1.2 (P=0.02).

Patients with a TRV ≥ 2.5 m/s had significantly lower plasma arginine concentration (P<0.001) and biomarkers of global arginine bioavailability, including plasma arginine/ornithine ratio (P=0.01) and mean plasma global arginine bioavailability ratio (arginine/ornithine + citrulline ratio, P=0.04).

These patients also had significantly higher arginase concentration and activity than patients with TRV below 2.5 m/s (P=0.02).

These findings prompted the researchers to evaluate the relationship between arginase activity/concentration and clinical and laboratory markers of disease severity.

They found that arginase concentration was significantly correlated with several parameters of cardiovascular function, including left atrial volume (echo and MRI), right atrial volume (MRI), LV end systolic volume (echo and MRI), LV end diastolic volume (echo and MRI), LV mass (echo and MRI), and cardiac index (echo).

Arginase concentration was also significantly correlated with white blood cell count (P=0.03), plasma arginine (P=0.0002), arginine/ornithine (P=0.01) and arginine/ornithine + citrulline ratios (P=0.05), and hemoglobin (P=0.02), bilirubin (P=0.02), and LDH levels (P=0.001).

In multiple regression analysis, only cardiac index, bilirubin, and plasma arginine/ornithine ratio remained significantly associated with arginase concentration (P<0.05 for all).

Arginase activity was significantly correlated with several biomarkers of coagulation, including monoclonal prothrombin fragment 1.2 (P=0.04), thrombin-antithrombin complex (P=0.04), and tissue factor concentration (P=0.02).

Considering these results together, the researchers said it seems low arginine bioavailability contributes to cardiopulmonary dysfunction in patients with β-thalassemia.

Anopheles stephensi mosquito

Photo courtesy of the CDC

Repeat infection with malaria parasites might make mosquitoes more dangerous, according to a study published in PLOS Pathogens.

The research showed that individual Anopheles mosquitoes can accumulate infections with different strains of malaria parasites, an existing malaria infection makes mosquitoes more susceptible to a second infection, and infections reach higher densities when another strain is already present.

These phenomena could promote the spread of drug-resistant malaria, according to investigators.

Laura Pollitt, PhD, of the University of Edinburgh in the UK, and her colleagues conducted this research.

They wanted to determine if and how mosquitoes can be infected with different strains of Plasmodium parasites, how such heterogeneous parasites interact in the insects, and whether such interactions affect the transmission of malaria to vertebrate hosts.

The investigators set up cages of female Anopheles stephensi mosquitoes and allowed them, at defined times, to feed on mice infected with 2 different Plasmodium chabaudi strains—AJ and ER.

This study design allowed the team to examine how the presence of a co-infecting strain affects parasites that enter the vector first and second, and to test whether co-infection impacts mosquito survival.

The investigators found that mosquitoes can accumulate mixed-strain malaria infections after feeding on multiple hosts. And parasites have a greater chance of establishing a secondary infection if another Plasmodium strain is already present in a mosquito.

Moreover, the presence of the primary infection facilitated replication of the secondary infection while the first infection developed as normal. This resulted in doubly infected mosquitoes having substantially higher parasite loads.

The investigators noted that the large parasite numbers do not appear to kill the insects. And, because it is expected that mosquitoes carrying more parasites are more likely to transmit malaria to vertebrates, mosquitoes taking multiple infective bites might disproportionally contribute to malaria transmission.

This, in turn, would increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains.

Anopheles stephensi mosquito

Photo courtesy of the CDC

Repeat infection with malaria parasites might make mosquitoes more dangerous, according to a study published in PLOS Pathogens.

The research showed that individual Anopheles mosquitoes can accumulate infections with different strains of malaria parasites, an existing malaria infection makes mosquitoes more susceptible to a second infection, and infections reach higher densities when another strain is already present.

These phenomena could promote the spread of drug-resistant malaria, according to investigators.

Laura Pollitt, PhD, of the University of Edinburgh in the UK, and her colleagues conducted this research.

They wanted to determine if and how mosquitoes can be infected with different strains of Plasmodium parasites, how such heterogeneous parasites interact in the insects, and whether such interactions affect the transmission of malaria to vertebrate hosts.

The investigators set up cages of female Anopheles stephensi mosquitoes and allowed them, at defined times, to feed on mice infected with 2 different Plasmodium chabaudi strains—AJ and ER.

This study design allowed the team to examine how the presence of a co-infecting strain affects parasites that enter the vector first and second, and to test whether co-infection impacts mosquito survival.

The investigators found that mosquitoes can accumulate mixed-strain malaria infections after feeding on multiple hosts. And parasites have a greater chance of establishing a secondary infection if another Plasmodium strain is already present in a mosquito.

Moreover, the presence of the primary infection facilitated replication of the secondary infection while the first infection developed as normal. This resulted in doubly infected mosquitoes having substantially higher parasite loads.

The investigators noted that the large parasite numbers do not appear to kill the insects. And, because it is expected that mosquitoes carrying more parasites are more likely to transmit malaria to vertebrates, mosquitoes taking multiple infective bites might disproportionally contribute to malaria transmission.

This, in turn, would increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains.

Anopheles stephensi mosquito

Photo courtesy of the CDC

Repeat infection with malaria parasites might make mosquitoes more dangerous, according to a study published in PLOS Pathogens.

The research showed that individual Anopheles mosquitoes can accumulate infections with different strains of malaria parasites, an existing malaria infection makes mosquitoes more susceptible to a second infection, and infections reach higher densities when another strain is already present.

These phenomena could promote the spread of drug-resistant malaria, according to investigators.

Laura Pollitt, PhD, of the University of Edinburgh in the UK, and her colleagues conducted this research.

They wanted to determine if and how mosquitoes can be infected with different strains of Plasmodium parasites, how such heterogeneous parasites interact in the insects, and whether such interactions affect the transmission of malaria to vertebrate hosts.

The investigators set up cages of female Anopheles stephensi mosquitoes and allowed them, at defined times, to feed on mice infected with 2 different Plasmodium chabaudi strains—AJ and ER.

This study design allowed the team to examine how the presence of a co-infecting strain affects parasites that enter the vector first and second, and to test whether co-infection impacts mosquito survival.

The investigators found that mosquitoes can accumulate mixed-strain malaria infections after feeding on multiple hosts. And parasites have a greater chance of establishing a secondary infection if another Plasmodium strain is already present in a mosquito.

Moreover, the presence of the primary infection facilitated replication of the secondary infection while the first infection developed as normal. This resulted in doubly infected mosquitoes having substantially higher parasite loads.

The investigators noted that the large parasite numbers do not appear to kill the insects. And, because it is expected that mosquitoes carrying more parasites are more likely to transmit malaria to vertebrates, mosquitoes taking multiple infective bites might disproportionally contribute to malaria transmission.

This, in turn, would increase rates of mixed infections in vertebrate hosts, with implications for the evolution of parasite virulence and the spread of drug-resistant strains.

Revision of the Health Insurance Portability and Accountability Act (HIPAA) rules has prompted numerous questions about business associates (BAs) and business associate agreements (BAAs). Apparently there is confusion about exactly which businesses qualify as BAs and how your BAAs should be modified to reflect the new provisions.

The criteria for identifying BAs are admittedly vague: The act defines them as nonemployees, performing “functions or activities” on behalf of the “covered entity” (your practice) that involve “creating, receiving, maintaining, or transmitting” personal health information (PHI).

Clearly, answering and billing services, independent transcriptionists, hardware and software companies, and any other vendors involved in creating or maintaining your medical records always qualify as BAs. Other businesses may or may not qualify, depending on whether they need direct access to PHI in order to provide their service. These include practice management consultants, attorneys, companies that store or microfilm medical records, and record-shredding services.

Specialty pharmacies are seldom mentioned in the BA discussion, but they probably should be. Pharmaceutical manufacturers are increasingly using them as intermediaries for their products – particularly the more expensive ones, such as biologics. Many of them ship products directly to patients, for which they require home addresses and other personal information, and in order to file payment paperwork and claim forms, they usually request diagnoses and associated medical information. By any reasonable interpretation of the new rules, this makes them BAs, and you should have BAAs in place before allowing them to fill your prescriptions.

To further complicate the situation, manufacturers and insurers routinely compile information about the real world uses of their products. To that end, they often ask specialty pharmacies to provide them with any patient data that they collect. Under the new rules, patients may restrict any PHI shared with third parties when patients pay for the drugs or services themselves. Your specialty pharmacy BAA should include a provision noting that the pharmacy is forbidden from disclosing any data to pharmaceutical companies or insurers from patients who self-pay and request confidentiality.

Mail carriers, package delivery people, cleaning services, copier repairmen, bank employees, and the like are not considered BAs. While they might conceivably come in contact with PHI on occasion, they don’t need it to do their job. You are required to use “reasonable diligence” in limiting the PHI that these folks may encounter, but you do not need to enter into written BA agreements with them.

Independent contractors who work within your practice – aestheticians and physical therapists, for example – are not considered BAs either, and do not need to sign a BA agreement. Just train them, as you do your employees.

Another source of confusion is the provision in the new rules that makes BAs directly responsible for their own HIPAA violations. While this might seem to eliminate the need for BAAs entirely, unfortunately that is not the case. In fact, even more responsibility has been placed on physicians for confidentiality breaches committed by their BAs. It is not enough to simply have a BAA in place; you are expected to use “reasonable diligence” in monitoring the work of your BAs. While BAs and their subcontractors are responsible for their own actions, the primary responsibility remains with you. Furthermore, you now must assume the worst-case scenario. Previously, when PHI was compromised, you would have to notify affected patients (and the government) only if there was a “significant risk of financial or reputational harm”; but now, any incident involving patient records is assumed to be a breach, and must be reported. Failure to do so could subject your practice, as well as the contractor, to significant fines.

If you haven’t yet revised your Notice of Privacy Practices (NPP) to explain your relationships with BAs, and their status under the new rules, do it now. (You should have done it last September.) You need to explain the breach notification process too, as well as the new patient rights mentioned above. You must post your revised NPP in your office, and make copies available there, but you need not mail a copy to every patient.

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

Revision of the Health Insurance Portability and Accountability Act (HIPAA) rules has prompted numerous questions about business associates (BAs) and business associate agreements (BAAs). Apparently there is confusion about exactly which businesses qualify as BAs and how your BAAs should be modified to reflect the new provisions.

The criteria for identifying BAs are admittedly vague: The act defines them as nonemployees, performing “functions or activities” on behalf of the “covered entity” (your practice) that involve “creating, receiving, maintaining, or transmitting” personal health information (PHI).

Clearly, answering and billing services, independent transcriptionists, hardware and software companies, and any other vendors involved in creating or maintaining your medical records always qualify as BAs. Other businesses may or may not qualify, depending on whether they need direct access to PHI in order to provide their service. These include practice management consultants, attorneys, companies that store or microfilm medical records, and record-shredding services.

Specialty pharmacies are seldom mentioned in the BA discussion, but they probably should be. Pharmaceutical manufacturers are increasingly using them as intermediaries for their products – particularly the more expensive ones, such as biologics. Many of them ship products directly to patients, for which they require home addresses and other personal information, and in order to file payment paperwork and claim forms, they usually request diagnoses and associated medical information. By any reasonable interpretation of the new rules, this makes them BAs, and you should have BAAs in place before allowing them to fill your prescriptions.

To further complicate the situation, manufacturers and insurers routinely compile information about the real world uses of their products. To that end, they often ask specialty pharmacies to provide them with any patient data that they collect. Under the new rules, patients may restrict any PHI shared with third parties when patients pay for the drugs or services themselves. Your specialty pharmacy BAA should include a provision noting that the pharmacy is forbidden from disclosing any data to pharmaceutical companies or insurers from patients who self-pay and request confidentiality.

Mail carriers, package delivery people, cleaning services, copier repairmen, bank employees, and the like are not considered BAs. While they might conceivably come in contact with PHI on occasion, they don’t need it to do their job. You are required to use “reasonable diligence” in limiting the PHI that these folks may encounter, but you do not need to enter into written BA agreements with them.

Independent contractors who work within your practice – aestheticians and physical therapists, for example – are not considered BAs either, and do not need to sign a BA agreement. Just train them, as you do your employees.

Another source of confusion is the provision in the new rules that makes BAs directly responsible for their own HIPAA violations. While this might seem to eliminate the need for BAAs entirely, unfortunately that is not the case. In fact, even more responsibility has been placed on physicians for confidentiality breaches committed by their BAs. It is not enough to simply have a BAA in place; you are expected to use “reasonable diligence” in monitoring the work of your BAs. While BAs and their subcontractors are responsible for their own actions, the primary responsibility remains with you. Furthermore, you now must assume the worst-case scenario. Previously, when PHI was compromised, you would have to notify affected patients (and the government) only if there was a “significant risk of financial or reputational harm”; but now, any incident involving patient records is assumed to be a breach, and must be reported. Failure to do so could subject your practice, as well as the contractor, to significant fines.

If you haven’t yet revised your Notice of Privacy Practices (NPP) to explain your relationships with BAs, and their status under the new rules, do it now. (You should have done it last September.) You need to explain the breach notification process too, as well as the new patient rights mentioned above. You must post your revised NPP in your office, and make copies available there, but you need not mail a copy to every patient.

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

Revision of the Health Insurance Portability and Accountability Act (HIPAA) rules has prompted numerous questions about business associates (BAs) and business associate agreements (BAAs). Apparently there is confusion about exactly which businesses qualify as BAs and how your BAAs should be modified to reflect the new provisions.

The criteria for identifying BAs are admittedly vague: The act defines them as nonemployees, performing “functions or activities” on behalf of the “covered entity” (your practice) that involve “creating, receiving, maintaining, or transmitting” personal health information (PHI).

Clearly, answering and billing services, independent transcriptionists, hardware and software companies, and any other vendors involved in creating or maintaining your medical records always qualify as BAs. Other businesses may or may not qualify, depending on whether they need direct access to PHI in order to provide their service. These include practice management consultants, attorneys, companies that store or microfilm medical records, and record-shredding services.

Specialty pharmacies are seldom mentioned in the BA discussion, but they probably should be. Pharmaceutical manufacturers are increasingly using them as intermediaries for their products – particularly the more expensive ones, such as biologics. Many of them ship products directly to patients, for which they require home addresses and other personal information, and in order to file payment paperwork and claim forms, they usually request diagnoses and associated medical information. By any reasonable interpretation of the new rules, this makes them BAs, and you should have BAAs in place before allowing them to fill your prescriptions.

To further complicate the situation, manufacturers and insurers routinely compile information about the real world uses of their products. To that end, they often ask specialty pharmacies to provide them with any patient data that they collect. Under the new rules, patients may restrict any PHI shared with third parties when patients pay for the drugs or services themselves. Your specialty pharmacy BAA should include a provision noting that the pharmacy is forbidden from disclosing any data to pharmaceutical companies or insurers from patients who self-pay and request confidentiality.

Mail carriers, package delivery people, cleaning services, copier repairmen, bank employees, and the like are not considered BAs. While they might conceivably come in contact with PHI on occasion, they don’t need it to do their job. You are required to use “reasonable diligence” in limiting the PHI that these folks may encounter, but you do not need to enter into written BA agreements with them.

Independent contractors who work within your practice – aestheticians and physical therapists, for example – are not considered BAs either, and do not need to sign a BA agreement. Just train them, as you do your employees.

Another source of confusion is the provision in the new rules that makes BAs directly responsible for their own HIPAA violations. While this might seem to eliminate the need for BAAs entirely, unfortunately that is not the case. In fact, even more responsibility has been placed on physicians for confidentiality breaches committed by their BAs. It is not enough to simply have a BAA in place; you are expected to use “reasonable diligence” in monitoring the work of your BAs. While BAs and their subcontractors are responsible for their own actions, the primary responsibility remains with you. Furthermore, you now must assume the worst-case scenario. Previously, when PHI was compromised, you would have to notify affected patients (and the government) only if there was a “significant risk of financial or reputational harm”; but now, any incident involving patient records is assumed to be a breach, and must be reported. Failure to do so could subject your practice, as well as the contractor, to significant fines.

If you haven’t yet revised your Notice of Privacy Practices (NPP) to explain your relationships with BAs, and their status under the new rules, do it now. (You should have done it last September.) You need to explain the breach notification process too, as well as the new patient rights mentioned above. You must post your revised NPP in your office, and make copies available there, but you need not mail a copy to every patient.

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

Adolescents with restrictive eating disorders had high rates of psychiatric comorbidity and medication use, reported Dr. Maria C. Monge of the division of adolescent/young adult medicine at Boston Children’s Hospital, and her coauthors.

In an analysis of 635 patients (359 of whom had follow-up after 1 year), 20.4% were taking psychopharmacologic medication at intake and 58.7% were taking medication at 1 year (P < .0001). The presence of psychiatric comorbidity was significantly associated with medication use (odds ratio, 10.0).

In 256 patients in which there was additional information about psychopharmacologic medication use, selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) was the most common (83%), followed by anxiolytic (18%), antipsychotic (17%), other antidepressant (15%), mood stabilizer (8%), other psychopharmacologic medication not listed elsewhere (cyproheptadine, gabapentin, and guanfacine; 6%), stimulant (6%), and atomoxetine (1%). A total of 30% of patients on these medications were taking two or more at 1-year follow-up.

At 1-year follow-up, 63% of patients had a psychiatric comorbidity. Anxiety was the most common at 44%, followed by depression in 26%. Less-common diagnoses were attention-deficit/hyperactivity disorder in 2%, bipolar disorder in 0.5%, and other diagnoses in 2% including posttraumatic stress disorder, personality disorder, drug abuse, conversion disorder, trichotillomania, oppositional defiant disorder, and body dysmorphic disorder.

“Psychopharmacologic medications may be appropriate for treatment of comorbid conditions in these patients; however, it is unclear from existing studies if the addition of medication changes patients’ trajectories and provides an effective adjunct to weight restoration,” Dr. Monge and her colleagues said. “Continued investigation is needed to ensure [whether] the desired outcomes of the medications are being met, and the risks and rewards of such medications are fully understood in these patients.”

Read the full article here

Adolescents with restrictive eating disorders had high rates of psychiatric comorbidity and medication use, reported Dr. Maria C. Monge of the division of adolescent/young adult medicine at Boston Children’s Hospital, and her coauthors.

In an analysis of 635 patients (359 of whom had follow-up after 1 year), 20.4% were taking psychopharmacologic medication at intake and 58.7% were taking medication at 1 year (P < .0001). The presence of psychiatric comorbidity was significantly associated with medication use (odds ratio, 10.0).

In 256 patients in which there was additional information about psychopharmacologic medication use, selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) was the most common (83%), followed by anxiolytic (18%), antipsychotic (17%), other antidepressant (15%), mood stabilizer (8%), other psychopharmacologic medication not listed elsewhere (cyproheptadine, gabapentin, and guanfacine; 6%), stimulant (6%), and atomoxetine (1%). A total of 30% of patients on these medications were taking two or more at 1-year follow-up.

At 1-year follow-up, 63% of patients had a psychiatric comorbidity. Anxiety was the most common at 44%, followed by depression in 26%. Less-common diagnoses were attention-deficit/hyperactivity disorder in 2%, bipolar disorder in 0.5%, and other diagnoses in 2% including posttraumatic stress disorder, personality disorder, drug abuse, conversion disorder, trichotillomania, oppositional defiant disorder, and body dysmorphic disorder.

“Psychopharmacologic medications may be appropriate for treatment of comorbid conditions in these patients; however, it is unclear from existing studies if the addition of medication changes patients’ trajectories and provides an effective adjunct to weight restoration,” Dr. Monge and her colleagues said. “Continued investigation is needed to ensure [whether] the desired outcomes of the medications are being met, and the risks and rewards of such medications are fully understood in these patients.”

Read the full article here

Adolescents with restrictive eating disorders had high rates of psychiatric comorbidity and medication use, reported Dr. Maria C. Monge of the division of adolescent/young adult medicine at Boston Children’s Hospital, and her coauthors.

In an analysis of 635 patients (359 of whom had follow-up after 1 year), 20.4% were taking psychopharmacologic medication at intake and 58.7% were taking medication at 1 year (P < .0001). The presence of psychiatric comorbidity was significantly associated with medication use (odds ratio, 10.0).

In 256 patients in which there was additional information about psychopharmacologic medication use, selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) was the most common (83%), followed by anxiolytic (18%), antipsychotic (17%), other antidepressant (15%), mood stabilizer (8%), other psychopharmacologic medication not listed elsewhere (cyproheptadine, gabapentin, and guanfacine; 6%), stimulant (6%), and atomoxetine (1%). A total of 30% of patients on these medications were taking two or more at 1-year follow-up.

At 1-year follow-up, 63% of patients had a psychiatric comorbidity. Anxiety was the most common at 44%, followed by depression in 26%. Less-common diagnoses were attention-deficit/hyperactivity disorder in 2%, bipolar disorder in 0.5%, and other diagnoses in 2% including posttraumatic stress disorder, personality disorder, drug abuse, conversion disorder, trichotillomania, oppositional defiant disorder, and body dysmorphic disorder.

“Psychopharmacologic medications may be appropriate for treatment of comorbid conditions in these patients; however, it is unclear from existing studies if the addition of medication changes patients’ trajectories and provides an effective adjunct to weight restoration,” Dr. Monge and her colleagues said. “Continued investigation is needed to ensure [whether] the desired outcomes of the medications are being met, and the risks and rewards of such medications are fully understood in these patients.”

Read the full article here

“Alien Physician” – thus am I ordained by the document that allows me to train in America. I am the International Medical Graduate. This is my story.

I came from poverty and hardship. In other cases, I came from wealth and privilege. Regardless, I clawed my way over staggering numbers of competitors to earn my shot at a medical education. Back home, I was top of my class, fresh out of medical school. In other cases, I was a respected practitioner with a wealth of experience. Now I am a blank slate.

I am here because I heard of a place where questions were encouraged and boundaries pushed. Or I am here because I learned of the American dream. They told me I would be judged for my merit here and nothing else. I have escaped persecution, war, nepotism, or perhaps just a bogged-down system to get here.

Although I have taken the same tests as you, my resume comes with an asterisk. I have had to prove myself by rising to a standard higher than that expected of my peers. Much of my time and peace of mind are consumed jumping through bureaucratic hoops in order to continue my stay. For every one of me you see, there is at least one more who was forced to give up on his or her dream midway.

Know this, however – I appreciate working in a system where the team is greater than the individual, where no job is menial, where the ability to make choices about your health is yours alone, to be shared should you need to.

Know that I am good company, although my jokes sometimes fall flat in the space between our two cultures. Learning new things about your country and its people makes me feel young again.

Know that I have a keen appreciation of how important cultural nuance is to the doctor-patient relationship, even if I come across as ignorant. I have gained this understanding not by reading about it in a book, but by living it.

Know that nothing is more important to me than the health of my patients, and that my being a foreigner does not mean your child will receive anything less than my very best.

Most importantly, know that I feel blessed to be here. While my journey is still uphill, I have no regrets. If I were not made of hard stuff, I would not be here. Although I may grumble, I shall endeavor to accept my lot with grace and humility in the knowledge that I have earned the right to practice the subject that I love and the cognizance that not everyone would open their arms to outsiders the way you have. It has meant the world to me. Working with you has opened my eyes to things I did not see before and has inspired me to be a better doctor. I hope in some small way my presence here affords you that same inspiration.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, N.H. when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del.

“Alien Physician” – thus am I ordained by the document that allows me to train in America. I am the International Medical Graduate. This is my story.

I came from poverty and hardship. In other cases, I came from wealth and privilege. Regardless, I clawed my way over staggering numbers of competitors to earn my shot at a medical education. Back home, I was top of my class, fresh out of medical school. In other cases, I was a respected practitioner with a wealth of experience. Now I am a blank slate.

I am here because I heard of a place where questions were encouraged and boundaries pushed. Or I am here because I learned of the American dream. They told me I would be judged for my merit here and nothing else. I have escaped persecution, war, nepotism, or perhaps just a bogged-down system to get here.

Although I have taken the same tests as you, my resume comes with an asterisk. I have had to prove myself by rising to a standard higher than that expected of my peers. Much of my time and peace of mind are consumed jumping through bureaucratic hoops in order to continue my stay. For every one of me you see, there is at least one more who was forced to give up on his or her dream midway.

Know this, however – I appreciate working in a system where the team is greater than the individual, where no job is menial, where the ability to make choices about your health is yours alone, to be shared should you need to.

Know that I am good company, although my jokes sometimes fall flat in the space between our two cultures. Learning new things about your country and its people makes me feel young again.

Know that I have a keen appreciation of how important cultural nuance is to the doctor-patient relationship, even if I come across as ignorant. I have gained this understanding not by reading about it in a book, but by living it.

Know that nothing is more important to me than the health of my patients, and that my being a foreigner does not mean your child will receive anything less than my very best.

Most importantly, know that I feel blessed to be here. While my journey is still uphill, I have no regrets. If I were not made of hard stuff, I would not be here. Although I may grumble, I shall endeavor to accept my lot with grace and humility in the knowledge that I have earned the right to practice the subject that I love and the cognizance that not everyone would open their arms to outsiders the way you have. It has meant the world to me. Working with you has opened my eyes to things I did not see before and has inspired me to be a better doctor. I hope in some small way my presence here affords you that same inspiration.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, N.H. when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del.

“Alien Physician” – thus am I ordained by the document that allows me to train in America. I am the International Medical Graduate. This is my story.

I came from poverty and hardship. In other cases, I came from wealth and privilege. Regardless, I clawed my way over staggering numbers of competitors to earn my shot at a medical education. Back home, I was top of my class, fresh out of medical school. In other cases, I was a respected practitioner with a wealth of experience. Now I am a blank slate.

I am here because I heard of a place where questions were encouraged and boundaries pushed. Or I am here because I learned of the American dream. They told me I would be judged for my merit here and nothing else. I have escaped persecution, war, nepotism, or perhaps just a bogged-down system to get here.

Although I have taken the same tests as you, my resume comes with an asterisk. I have had to prove myself by rising to a standard higher than that expected of my peers. Much of my time and peace of mind are consumed jumping through bureaucratic hoops in order to continue my stay. For every one of me you see, there is at least one more who was forced to give up on his or her dream midway.

Know this, however – I appreciate working in a system where the team is greater than the individual, where no job is menial, where the ability to make choices about your health is yours alone, to be shared should you need to.

Know that I am good company, although my jokes sometimes fall flat in the space between our two cultures. Learning new things about your country and its people makes me feel young again.

Know that I have a keen appreciation of how important cultural nuance is to the doctor-patient relationship, even if I come across as ignorant. I have gained this understanding not by reading about it in a book, but by living it.

Know that nothing is more important to me than the health of my patients, and that my being a foreigner does not mean your child will receive anything less than my very best.

Most importantly, know that I feel blessed to be here. While my journey is still uphill, I have no regrets. If I were not made of hard stuff, I would not be here. Although I may grumble, I shall endeavor to accept my lot with grace and humility in the knowledge that I have earned the right to practice the subject that I love and the cognizance that not everyone would open their arms to outsiders the way you have. It has meant the world to me. Working with you has opened my eyes to things I did not see before and has inspired me to be a better doctor. I hope in some small way my presence here affords you that same inspiration.

Dr. Behere was a pediatric resident at the Children’s Hospital at Dartmouth, Lebanon, N.H. when he wrote this article. He is currently a first-year fellow in pediatric cardiology at the Nemours Cardiac Center at the Nemours/Alfred I. duPont Hospital for Children, Wilmington, Del.

Allergic contact dermatitis (ACD) is a common inflammatory skin condition that affects more than 14 million Americans each year.¹ It has been estimated that the economic burden of ACD is nearly $3 billion per year due to school absences, work time lost, and medical expenditures.^1,2 In fact, skin diseases rank second to traumatic injuries as the most common type of occupational disease.³ As dermatology residents, we will encounter many patients with ACD, a potentially debilitating skin condition. In this column, I will discuss the different types of ACD as well as their differential diagnoses and management options according to the American Academy of Allergy, Asthma & Immunology’s updated practice parameter for contact dermatitis.⁴ The 2015 American Contact Dermatitis Society (ACDS) Allergen of the Year and the ACDS’s Contact Allergen Management Program also will be discussed.

Clinical Presentation and Pathophysiology

Allergic contact dermatitis is a widespread skin condition characterized by erythematous and pruritic skin lesions that occur after contact with external stimuli.⁵ It is caused by a type IV, T cell–mediated, delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin and forms an antigen complex that subsequently leads to sensitization. Upon reexposure to the antigen, the sensitized T cells induce an inflammatory cascade causing the skin changes associated with ACD. Clinical presentations of ACD include vesicles and bullae with distinct angles, lines, and borders.⁶

Differential Diagnosis

In contrast to ACD, irritant contact dermatitis (the more common form of contact dermatitis) is a non–immune-modulated skin reaction that occurs when an individual is exposed to a substance that causes irritation and damage to the keratinocytes.^6,7 It can be an acute reaction to a household cleaning product or a chronic reaction to soap if the patient has had exposure to the product for a prolonged period of time.⁷ The clinical presentation of irritant contact dermatitis includes dry and fissured skin with less distinct borders and negative patch test results.⁶

Some other skin diseases that should be considered in the differential diagnosis for suspected ACD include atopic dermatitis, dyshidrotic eczema, inverse psoriasis, latex allergy, palmoplantar psoriasis, scabies, and tinea pedis.⁵ When ACD is suspected, our diagnostic approach as dermatology residents should be based on a combination of the following factors: the clinical features of the skin reaction (eg, morphology, location, symptoms), the patient’s history of exposure to an alleged allergen and lack of exposure after treatment and/or avoidance, patch test results, laboratory test results, and/or histopathologic examination to exclude other disorders with similar clinical features.⁸

Management

Localized acute lesions of ACD can be successfully treated with mid- or high-potency topical steroids such as triamcinolone 0.1% or clobetasol 0.05%. If an extensive area of the skin (>20%) is affected, systemic steroid therapy often is required, generally offering relief within 12 to 24 hours. Caution should be taken when prescribing oral prednisone, such as for poison ivy, as it should be tapered over a few weeks to prevent rebound dermatitis. If treatment fails and the diagnosis or specific allergen remains unknown, patch testing should be performed.^3,5

Updated Practice Parameter

Practice parameters for contact dermatitis were updated in 2015, as commissioned by the Joint Task Force on Practice Parameters, to address recent advances in the field of contact dermatitis and the most recommended methods for diagnosis and management based on the current scientific literature.⁴ Prior to this update, the most recent recommendations were from 2006.³

Since the publication of the original practice parameter, new questions have been addressed related to emerging clinical problems such as preoperative screening and postimplantation patch testing for metal allergy in patients undergoing joint replacement surgery. In the updated practice parameter, statements have been added that more comprehensively address evaluation and management of occupational contact dermatitis.⁴ The potential benefits and limitations of drug patch testing in patients with maculopapular rashes, erythroderma, and nonimmediate cutaneous reactions also have been addressed. New summary statements have been included that make recommendations on the management of ACD, particularly avoidance and prevention.⁴

ACDS Allergen of the Year

The purpose of this “award” is to recognize the agents that cause the most remarkable clinical effects, those that draw less attention, or those that exhibit exposure patterns that have changed. The ACDS’s 2015 Allergen of the Year is formaldehyde, an inexpensive biocidal preservative used in a wide range of products such as tissue specimen and cadaveric preservation solutions, nail polish, hair-smoothing treatments, and wrinkle-free fabrics.⁹

Formaldehyde-releasing preservatives (FRPs) are among the leading contact allergens and are found in many personal hygiene products, medications, and household cleansers.⁸ Specific sources of FRPs include shampoos, bodywashes, hand soaps, lotions, creams, baby wipes, mascara, disinfectants, fabric softeners, topical wart remedies, adhesives, and tissue specimen preservation solutions.^10-13 According to de Groot et al,¹⁴ the US Food and Drug Administration’s Voluntary Cosmetic Registration Program database has estimated that approximately 20% of personal hygiene products and cosmetics contain an FRP, with imidazolidinyl urea as the most common.

It is important for patients to be aware of sources of formaldehyde exposure and understand that many products containing formaldehyde or FRPs may not list this information on their labels. In fact, one study reported that 33% of 67 moisturizers evaluated did not have proper labeling with regard to their formaldehyde/FRP content.¹⁵

Contact Allergen Management Program

During medical school I served as the Dermatology Interest Group Contact Dermatitis Awareness Chair at the University of Texas Medical Branch (Galveston, Texas) and was fortunate to have attended the annual meeting of the ACDS where I learned about the ACDS Contact Allergen Management Program (CAMP), an online resource for dermatologists to access that provides patients a printout list of allergen and cross-reactivity information for more than 1200 products (http://www.contactderm.org/i4a/pages/indexcfm?pageID=3489). This information helps consumers to choose the right products based on their allergies.

Final Thoughts

A thorough review of a patient’s medical history and, if needed, skin patch testing can identify the responsible allergen and initiate an appropriate avoidance plan for the patient. With appropriate avoidance, patients can achieve resolution of their dermatitis and prevent further episodes to substantially improve their quality of life and decrease health care costs.¹ If left untreated, ACD can evolve from an acute form to a subacute form and eventually chronic eczematous dermatitis or progression to systemic disease.^16,17 Allergic contact dermatitis can negatively impact an individual’s health-related quality of life, particularly in social functioning and psychological well-being.^18,19 Therefore, it is pertinent in our role as dermatology residents to recognize ACD before its progression to a chronic state.

Allergic contact dermatitis (ACD) is a common inflammatory skin condition that affects more than 14 million Americans each year.¹ It has been estimated that the economic burden of ACD is nearly $3 billion per year due to school absences, work time lost, and medical expenditures.^1,2 In fact, skin diseases rank second to traumatic injuries as the most common type of occupational disease.³ As dermatology residents, we will encounter many patients with ACD, a potentially debilitating skin condition. In this column, I will discuss the different types of ACD as well as their differential diagnoses and management options according to the American Academy of Allergy, Asthma & Immunology’s updated practice parameter for contact dermatitis.⁴ The 2015 American Contact Dermatitis Society (ACDS) Allergen of the Year and the ACDS’s Contact Allergen Management Program also will be discussed.

Clinical Presentation and Pathophysiology

Allergic contact dermatitis is a widespread skin condition characterized by erythematous and pruritic skin lesions that occur after contact with external stimuli.⁵ It is caused by a type IV, T cell–mediated, delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin and forms an antigen complex that subsequently leads to sensitization. Upon reexposure to the antigen, the sensitized T cells induce an inflammatory cascade causing the skin changes associated with ACD. Clinical presentations of ACD include vesicles and bullae with distinct angles, lines, and borders.⁶

Differential Diagnosis

In contrast to ACD, irritant contact dermatitis (the more common form of contact dermatitis) is a non–immune-modulated skin reaction that occurs when an individual is exposed to a substance that causes irritation and damage to the keratinocytes.^6,7 It can be an acute reaction to a household cleaning product or a chronic reaction to soap if the patient has had exposure to the product for a prolonged period of time.⁷ The clinical presentation of irritant contact dermatitis includes dry and fissured skin with less distinct borders and negative patch test results.⁶

Some other skin diseases that should be considered in the differential diagnosis for suspected ACD include atopic dermatitis, dyshidrotic eczema, inverse psoriasis, latex allergy, palmoplantar psoriasis, scabies, and tinea pedis.⁵ When ACD is suspected, our diagnostic approach as dermatology residents should be based on a combination of the following factors: the clinical features of the skin reaction (eg, morphology, location, symptoms), the patient’s history of exposure to an alleged allergen and lack of exposure after treatment and/or avoidance, patch test results, laboratory test results, and/or histopathologic examination to exclude other disorders with similar clinical features.⁸

Management

Localized acute lesions of ACD can be successfully treated with mid- or high-potency topical steroids such as triamcinolone 0.1% or clobetasol 0.05%. If an extensive area of the skin (>20%) is affected, systemic steroid therapy often is required, generally offering relief within 12 to 24 hours. Caution should be taken when prescribing oral prednisone, such as for poison ivy, as it should be tapered over a few weeks to prevent rebound dermatitis. If treatment fails and the diagnosis or specific allergen remains unknown, patch testing should be performed.^3,5

Updated Practice Parameter

Practice parameters for contact dermatitis were updated in 2015, as commissioned by the Joint Task Force on Practice Parameters, to address recent advances in the field of contact dermatitis and the most recommended methods for diagnosis and management based on the current scientific literature.⁴ Prior to this update, the most recent recommendations were from 2006.³

Since the publication of the original practice parameter, new questions have been addressed related to emerging clinical problems such as preoperative screening and postimplantation patch testing for metal allergy in patients undergoing joint replacement surgery. In the updated practice parameter, statements have been added that more comprehensively address evaluation and management of occupational contact dermatitis.⁴ The potential benefits and limitations of drug patch testing in patients with maculopapular rashes, erythroderma, and nonimmediate cutaneous reactions also have been addressed. New summary statements have been included that make recommendations on the management of ACD, particularly avoidance and prevention.⁴

ACDS Allergen of the Year

The purpose of this “award” is to recognize the agents that cause the most remarkable clinical effects, those that draw less attention, or those that exhibit exposure patterns that have changed. The ACDS’s 2015 Allergen of the Year is formaldehyde, an inexpensive biocidal preservative used in a wide range of products such as tissue specimen and cadaveric preservation solutions, nail polish, hair-smoothing treatments, and wrinkle-free fabrics.⁹

Formaldehyde-releasing preservatives (FRPs) are among the leading contact allergens and are found in many personal hygiene products, medications, and household cleansers.⁸ Specific sources of FRPs include shampoos, bodywashes, hand soaps, lotions, creams, baby wipes, mascara, disinfectants, fabric softeners, topical wart remedies, adhesives, and tissue specimen preservation solutions.^10-13 According to de Groot et al,¹⁴ the US Food and Drug Administration’s Voluntary Cosmetic Registration Program database has estimated that approximately 20% of personal hygiene products and cosmetics contain an FRP, with imidazolidinyl urea as the most common.

It is important for patients to be aware of sources of formaldehyde exposure and understand that many products containing formaldehyde or FRPs may not list this information on their labels. In fact, one study reported that 33% of 67 moisturizers evaluated did not have proper labeling with regard to their formaldehyde/FRP content.¹⁵

Contact Allergen Management Program

During medical school I served as the Dermatology Interest Group Contact Dermatitis Awareness Chair at the University of Texas Medical Branch (Galveston, Texas) and was fortunate to have attended the annual meeting of the ACDS where I learned about the ACDS Contact Allergen Management Program (CAMP), an online resource for dermatologists to access that provides patients a printout list of allergen and cross-reactivity information for more than 1200 products (http://www.contactderm.org/i4a/pages/indexcfm?pageID=3489). This information helps consumers to choose the right products based on their allergies.

Final Thoughts

A thorough review of a patient’s medical history and, if needed, skin patch testing can identify the responsible allergen and initiate an appropriate avoidance plan for the patient. With appropriate avoidance, patients can achieve resolution of their dermatitis and prevent further episodes to substantially improve their quality of life and decrease health care costs.¹ If left untreated, ACD can evolve from an acute form to a subacute form and eventually chronic eczematous dermatitis or progression to systemic disease.^16,17 Allergic contact dermatitis can negatively impact an individual’s health-related quality of life, particularly in social functioning and psychological well-being.^18,19 Therefore, it is pertinent in our role as dermatology residents to recognize ACD before its progression to a chronic state.

Allergic contact dermatitis (ACD) is a common inflammatory skin condition that affects more than 14 million Americans each year.¹ It has been estimated that the economic burden of ACD is nearly $3 billion per year due to school absences, work time lost, and medical expenditures.^1,2 In fact, skin diseases rank second to traumatic injuries as the most common type of occupational disease.³ As dermatology residents, we will encounter many patients with ACD, a potentially debilitating skin condition. In this column, I will discuss the different types of ACD as well as their differential diagnoses and management options according to the American Academy of Allergy, Asthma & Immunology’s updated practice parameter for contact dermatitis.⁴ The 2015 American Contact Dermatitis Society (ACDS) Allergen of the Year and the ACDS’s Contact Allergen Management Program also will be discussed.

Clinical Presentation and Pathophysiology

Allergic contact dermatitis is a widespread skin condition characterized by erythematous and pruritic skin lesions that occur after contact with external stimuli.⁵ It is caused by a type IV, T cell–mediated, delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin and forms an antigen complex that subsequently leads to sensitization. Upon reexposure to the antigen, the sensitized T cells induce an inflammatory cascade causing the skin changes associated with ACD. Clinical presentations of ACD include vesicles and bullae with distinct angles, lines, and borders.⁶

Differential Diagnosis

In contrast to ACD, irritant contact dermatitis (the more common form of contact dermatitis) is a non–immune-modulated skin reaction that occurs when an individual is exposed to a substance that causes irritation and damage to the keratinocytes.^6,7 It can be an acute reaction to a household cleaning product or a chronic reaction to soap if the patient has had exposure to the product for a prolonged period of time.⁷ The clinical presentation of irritant contact dermatitis includes dry and fissured skin with less distinct borders and negative patch test results.⁶

Some other skin diseases that should be considered in the differential diagnosis for suspected ACD include atopic dermatitis, dyshidrotic eczema, inverse psoriasis, latex allergy, palmoplantar psoriasis, scabies, and tinea pedis.⁵ When ACD is suspected, our diagnostic approach as dermatology residents should be based on a combination of the following factors: the clinical features of the skin reaction (eg, morphology, location, symptoms), the patient’s history of exposure to an alleged allergen and lack of exposure after treatment and/or avoidance, patch test results, laboratory test results, and/or histopathologic examination to exclude other disorders with similar clinical features.⁸

Management

Localized acute lesions of ACD can be successfully treated with mid- or high-potency topical steroids such as triamcinolone 0.1% or clobetasol 0.05%. If an extensive area of the skin (>20%) is affected, systemic steroid therapy often is required, generally offering relief within 12 to 24 hours. Caution should be taken when prescribing oral prednisone, such as for poison ivy, as it should be tapered over a few weeks to prevent rebound dermatitis. If treatment fails and the diagnosis or specific allergen remains unknown, patch testing should be performed.^3,5

Updated Practice Parameter

Practice parameters for contact dermatitis were updated in 2015, as commissioned by the Joint Task Force on Practice Parameters, to address recent advances in the field of contact dermatitis and the most recommended methods for diagnosis and management based on the current scientific literature.⁴ Prior to this update, the most recent recommendations were from 2006.³

Since the publication of the original practice parameter, new questions have been addressed related to emerging clinical problems such as preoperative screening and postimplantation patch testing for metal allergy in patients undergoing joint replacement surgery. In the updated practice parameter, statements have been added that more comprehensively address evaluation and management of occupational contact dermatitis.⁴ The potential benefits and limitations of drug patch testing in patients with maculopapular rashes, erythroderma, and nonimmediate cutaneous reactions also have been addressed. New summary statements have been included that make recommendations on the management of ACD, particularly avoidance and prevention.⁴

ACDS Allergen of the Year

The purpose of this “award” is to recognize the agents that cause the most remarkable clinical effects, those that draw less attention, or those that exhibit exposure patterns that have changed. The ACDS’s 2015 Allergen of the Year is formaldehyde, an inexpensive biocidal preservative used in a wide range of products such as tissue specimen and cadaveric preservation solutions, nail polish, hair-smoothing treatments, and wrinkle-free fabrics.⁹

Formaldehyde-releasing preservatives (FRPs) are among the leading contact allergens and are found in many personal hygiene products, medications, and household cleansers.⁸ Specific sources of FRPs include shampoos, bodywashes, hand soaps, lotions, creams, baby wipes, mascara, disinfectants, fabric softeners, topical wart remedies, adhesives, and tissue specimen preservation solutions.^10-13 According to de Groot et al,¹⁴ the US Food and Drug Administration’s Voluntary Cosmetic Registration Program database has estimated that approximately 20% of personal hygiene products and cosmetics contain an FRP, with imidazolidinyl urea as the most common.

It is important for patients to be aware of sources of formaldehyde exposure and understand that many products containing formaldehyde or FRPs may not list this information on their labels. In fact, one study reported that 33% of 67 moisturizers evaluated did not have proper labeling with regard to their formaldehyde/FRP content.¹⁵

Contact Allergen Management Program

During medical school I served as the Dermatology Interest Group Contact Dermatitis Awareness Chair at the University of Texas Medical Branch (Galveston, Texas) and was fortunate to have attended the annual meeting of the ACDS where I learned about the ACDS Contact Allergen Management Program (CAMP), an online resource for dermatologists to access that provides patients a printout list of allergen and cross-reactivity information for more than 1200 products (http://www.contactderm.org/i4a/pages/indexcfm?pageID=3489). This information helps consumers to choose the right products based on their allergies.

Final Thoughts

A thorough review of a patient’s medical history and, if needed, skin patch testing can identify the responsible allergen and initiate an appropriate avoidance plan for the patient. With appropriate avoidance, patients can achieve resolution of their dermatitis and prevent further episodes to substantially improve their quality of life and decrease health care costs.¹ If left untreated, ACD can evolve from an acute form to a subacute form and eventually chronic eczematous dermatitis or progression to systemic disease.^16,17 Allergic contact dermatitis can negatively impact an individual’s health-related quality of life, particularly in social functioning and psychological well-being.^18,19 Therefore, it is pertinent in our role as dermatology residents to recognize ACD before its progression to a chronic state.

Malaria parasite Plasmodium

falciparum

in a mouse liver

Image courtesy of Seattle

Biomedical Research Institute

A new compound can fight multidrug-resistant malaria, according to preclinical research published in Science Translational Medicine.

The compound, DSM265, targets DHODH, an enzyme involved in the malaria parasite’s production of nucleotides.

Experiments showed that DSM265 can target the parasite at both the blood and liver stages of infection. And the compound appeared to be safe.

Based on these results, DSM265 has advanced to clinical trials.

Investigators believe the drug could potentially be partnered with other antimalarials for a single-dose treatment or once-weekly prophylaxis.

“This is the first of a new class of molecules that’s going into humans,” said study author Pradipsinh Rathod, PhD, of the University of Washington in Seattle.

“Until now, everything else in humans has been variations of drugs that have been developed in the distant past.”

The investigators tested DSM265 in multiple models, including human cells, rodents, dogs, and monkeys.

DSM265 arrested growth of the Plasmodium falciparum parasite at both the blood and liver stages. And the drug was active against P falciparum strains that were resistant to chloroquine and pyrimethamine.

DSM265 also proved to be long-acting. Experiments suggested a dose of 200 mg to 400 mg would maintain therapeutic concentrations in humans for at least 8 days.

Repeated doses of DSM265, given to mice and dogs, did not cause major side effects. The researchers said DSM265 was well tolerated at all dose levels given to mice (25 to 200 mg/kg per day once daily for 7 days) and dogs (30 to 480 mg/kg every other day for 10 days).

None of the animals died, and there were no clinical effects observed in the mice. Dogs receiving the highest dose of DSM265 experienced vomiting, apparent loss of appetite, and a slight increase in bilirubin that was not accompanied by changes in any other liver function markers.

Dr Rathod said he hopes the development and discovery pipeline for DSM265 will pave the way for a faster and more collaborative drug development process in “the long war against malaria.”

In an attempt to accelerate the drug’s development, the investigators transferred their patent rights for DSM265 to the Medicines for Malaria Venture, a Bill & Melinda Gates Foundation-supported nonprofit that is leading some of the clinical and field trials.

Malaria parasite Plasmodium

falciparum

in a mouse liver

Image courtesy of Seattle

Biomedical Research Institute

A new compound can fight multidrug-resistant malaria, according to preclinical research published in Science Translational Medicine.

The compound, DSM265, targets DHODH, an enzyme involved in the malaria parasite’s production of nucleotides.

Experiments showed that DSM265 can target the parasite at both the blood and liver stages of infection. And the compound appeared to be safe.

Based on these results, DSM265 has advanced to clinical trials.

Investigators believe the drug could potentially be partnered with other antimalarials for a single-dose treatment or once-weekly prophylaxis.

“This is the first of a new class of molecules that’s going into humans,” said study author Pradipsinh Rathod, PhD, of the University of Washington in Seattle.

“Until now, everything else in humans has been variations of drugs that have been developed in the distant past.”

The investigators tested DSM265 in multiple models, including human cells, rodents, dogs, and monkeys.

DSM265 arrested growth of the Plasmodium falciparum parasite at both the blood and liver stages. And the drug was active against P falciparum strains that were resistant to chloroquine and pyrimethamine.

DSM265 also proved to be long-acting. Experiments suggested a dose of 200 mg to 400 mg would maintain therapeutic concentrations in humans for at least 8 days.

Repeated doses of DSM265, given to mice and dogs, did not cause major side effects. The researchers said DSM265 was well tolerated at all dose levels given to mice (25 to 200 mg/kg per day once daily for 7 days) and dogs (30 to 480 mg/kg every other day for 10 days).

None of the animals died, and there were no clinical effects observed in the mice. Dogs receiving the highest dose of DSM265 experienced vomiting, apparent loss of appetite, and a slight increase in bilirubin that was not accompanied by changes in any other liver function markers.

Dr Rathod said he hopes the development and discovery pipeline for DSM265 will pave the way for a faster and more collaborative drug development process in “the long war against malaria.”

In an attempt to accelerate the drug’s development, the investigators transferred their patent rights for DSM265 to the Medicines for Malaria Venture, a Bill & Melinda Gates Foundation-supported nonprofit that is leading some of the clinical and field trials.

Malaria parasite Plasmodium

falciparum

in a mouse liver

Image courtesy of Seattle

Biomedical Research Institute

A new compound can fight multidrug-resistant malaria, according to preclinical research published in Science Translational Medicine.

The compound, DSM265, targets DHODH, an enzyme involved in the malaria parasite’s production of nucleotides.

Experiments showed that DSM265 can target the parasite at both the blood and liver stages of infection. And the compound appeared to be safe.

Based on these results, DSM265 has advanced to clinical trials.

Investigators believe the drug could potentially be partnered with other antimalarials for a single-dose treatment or once-weekly prophylaxis.

“This is the first of a new class of molecules that’s going into humans,” said study author Pradipsinh Rathod, PhD, of the University of Washington in Seattle.

“Until now, everything else in humans has been variations of drugs that have been developed in the distant past.”

The investigators tested DSM265 in multiple models, including human cells, rodents, dogs, and monkeys.

DSM265 arrested growth of the Plasmodium falciparum parasite at both the blood and liver stages. And the drug was active against P falciparum strains that were resistant to chloroquine and pyrimethamine.

DSM265 also proved to be long-acting. Experiments suggested a dose of 200 mg to 400 mg would maintain therapeutic concentrations in humans for at least 8 days.

Repeated doses of DSM265, given to mice and dogs, did not cause major side effects. The researchers said DSM265 was well tolerated at all dose levels given to mice (25 to 200 mg/kg per day once daily for 7 days) and dogs (30 to 480 mg/kg every other day for 10 days).

None of the animals died, and there were no clinical effects observed in the mice. Dogs receiving the highest dose of DSM265 experienced vomiting, apparent loss of appetite, and a slight increase in bilirubin that was not accompanied by changes in any other liver function markers.

Dr Rathod said he hopes the development and discovery pipeline for DSM265 will pave the way for a faster and more collaborative drug development process in “the long war against malaria.”

In an attempt to accelerate the drug’s development, the investigators transferred their patent rights for DSM265 to the Medicines for Malaria Venture, a Bill & Melinda Gates Foundation-supported nonprofit that is leading some of the clinical and field trials.