Clinical question

Does early intensive reduction of blood pressure improve outcomes in patients with hemorrhagic strokes?

Bottom line

As compared with more conservative management, early intensive lowering of blood pressure (BP) for patients with spontaneous intracranial bleeds does not significantly decrease mortality. However, this approach may result in better functional outcomes and quality of life. (LOE = 1b-)

Reference

Anderson CS, Heeley E, Huang Y, et al, for the INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368(25):2355-2365.

Study design

Randomized controlled trial (nonblinded);

Allocation

(Uncertain)

Setting

Inpatient (ICU only)

Synopsis

Patients who presented with spontaneous intracranial hemorrhage within the previous 6 hours were randomly assigned, using concealed allocation, to receive intensive BP-lowering therapy (n = 1403) or standard BP management according to current guidelines (n = 1436). Patients with structural causes for the bleed, those who were in a deep coma, or those who required early hematoma evacuation were excluded. In the intensive treatment group, intravenous and oral BP medications were used to lower the systolic BP to less than 140 mmHg within 1 hour and maintain it at this level for 1 week. Those in the standard treatment group received BP-lowering agents only if their systolic BP was greater than 180 mmHg. The mean age of the patients in the 2 groups was 64 years and the median presenting Glasgow Coma Scale score was 14. As compared with the standard therapy group, the intensive treatment group started BP-lowering therapy earlier after onset of intracranial hemorrhage (4.0 hours vs 4.5 hours; P < .001) and was more likely to receive intravenous agents (90% vs 43%; P < .001). At 90 days, there was no difference in the primary outcome of death or major disability, defined as a score of 3 to 5 on the modified Rankin scale (0 to 6, where 0 indicates no symptoms and 6 indicates death). Overall, 12% of the patients in each group died. When looking at disability alone, the intensive treatment group had significantly lower modified Rankin scores than the standard therapy group (odds ratio = 0.87; 95% CI, 0.77-1.0; P = .04) and had higher health-related quality of life scores (0.60 vs 0.55; P = .002). As this trial was not masked, the possibility exists that patients in the 2 groups were managed differently beyond just the 2 BP-lowering strategies.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does early intensive reduction of blood pressure improve outcomes in patients with hemorrhagic strokes?

Bottom line

As compared with more conservative management, early intensive lowering of blood pressure (BP) for patients with spontaneous intracranial bleeds does not significantly decrease mortality. However, this approach may result in better functional outcomes and quality of life. (LOE = 1b-)

Reference

Anderson CS, Heeley E, Huang Y, et al, for the INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368(25):2355-2365.

Study design

Randomized controlled trial (nonblinded);

Allocation

(Uncertain)

Setting

Inpatient (ICU only)

Synopsis

Patients who presented with spontaneous intracranial hemorrhage within the previous 6 hours were randomly assigned, using concealed allocation, to receive intensive BP-lowering therapy (n = 1403) or standard BP management according to current guidelines (n = 1436). Patients with structural causes for the bleed, those who were in a deep coma, or those who required early hematoma evacuation were excluded. In the intensive treatment group, intravenous and oral BP medications were used to lower the systolic BP to less than 140 mmHg within 1 hour and maintain it at this level for 1 week. Those in the standard treatment group received BP-lowering agents only if their systolic BP was greater than 180 mmHg. The mean age of the patients in the 2 groups was 64 years and the median presenting Glasgow Coma Scale score was 14. As compared with the standard therapy group, the intensive treatment group started BP-lowering therapy earlier after onset of intracranial hemorrhage (4.0 hours vs 4.5 hours; P < .001) and was more likely to receive intravenous agents (90% vs 43%; P < .001). At 90 days, there was no difference in the primary outcome of death or major disability, defined as a score of 3 to 5 on the modified Rankin scale (0 to 6, where 0 indicates no symptoms and 6 indicates death). Overall, 12% of the patients in each group died. When looking at disability alone, the intensive treatment group had significantly lower modified Rankin scores than the standard therapy group (odds ratio = 0.87; 95% CI, 0.77-1.0; P = .04) and had higher health-related quality of life scores (0.60 vs 0.55; P = .002). As this trial was not masked, the possibility exists that patients in the 2 groups were managed differently beyond just the 2 BP-lowering strategies.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does early intensive reduction of blood pressure improve outcomes in patients with hemorrhagic strokes?

Bottom line

As compared with more conservative management, early intensive lowering of blood pressure (BP) for patients with spontaneous intracranial bleeds does not significantly decrease mortality. However, this approach may result in better functional outcomes and quality of life. (LOE = 1b-)

Reference

Anderson CS, Heeley E, Huang Y, et al, for the INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368(25):2355-2365.

Study design

Randomized controlled trial (nonblinded);

Allocation

(Uncertain)

Setting

Inpatient (ICU only)

Synopsis

Patients who presented with spontaneous intracranial hemorrhage within the previous 6 hours were randomly assigned, using concealed allocation, to receive intensive BP-lowering therapy (n = 1403) or standard BP management according to current guidelines (n = 1436). Patients with structural causes for the bleed, those who were in a deep coma, or those who required early hematoma evacuation were excluded. In the intensive treatment group, intravenous and oral BP medications were used to lower the systolic BP to less than 140 mmHg within 1 hour and maintain it at this level for 1 week. Those in the standard treatment group received BP-lowering agents only if their systolic BP was greater than 180 mmHg. The mean age of the patients in the 2 groups was 64 years and the median presenting Glasgow Coma Scale score was 14. As compared with the standard therapy group, the intensive treatment group started BP-lowering therapy earlier after onset of intracranial hemorrhage (4.0 hours vs 4.5 hours; P < .001) and was more likely to receive intravenous agents (90% vs 43%; P < .001). At 90 days, there was no difference in the primary outcome of death or major disability, defined as a score of 3 to 5 on the modified Rankin scale (0 to 6, where 0 indicates no symptoms and 6 indicates death). Overall, 12% of the patients in each group died. When looking at disability alone, the intensive treatment group had significantly lower modified Rankin scores than the standard therapy group (odds ratio = 0.87; 95% CI, 0.77-1.0; P = .04) and had higher health-related quality of life scores (0.60 vs 0.55; P = .002). As this trial was not masked, the possibility exists that patients in the 2 groups were managed differently beyond just the 2 BP-lowering strategies.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

We live in an increasingly social and connected world. As such, doctor-patient online communication will become more common. As I noted in my last column, many physicians see online communication as a minefield of potential patient privacy violations, and they are reluctant to use it. Rather than avoid it for fear of committing a privacy violation, I hope all physicians will educate themselves on how to communicate online safely and effectively. To this end, I’m providing some examples of online questions you will likely encounter, with sample responses.

• A nonpatient asks you to make a diagnosis online. As a dermatologist who is active in social media, I often have nonpatients send me photos of their skin conditions requesting a diagnosis.

Sample question: "I’ve attached a photo of a mole on my leg. Does it look OK to you, Doc? Could it be cancerous?"

Sample response: "Thank you for sending me the picture. Without an established doctor-patient relationship, I’m unable to provide a diagnosis. I recommend you make an appointment with your dermatologist. If you don’t have one, here’s a link to the American Academy of Dermatology website where you can enter your ZIP code to find a dermatologist near you."

• A nonpatient asks your opinion about symptoms he is experiencing.

Sample question: "I’ve been experiencing bouts of diarrhea and stomach cramping and think I have celiac disease. I’m going to stop eating gluten. Do you think that’s a good idea?"

Sample response: "I’m sorry you’ve been unwell. Unfortunately, I cannot provide medical advice to you since we don’t have an established doctor-patient relationship. I can tell you, however, that diarrhea and cramping can be symptomatic of many conditions including, but not limited to celiac disease, irritable bowel syndrome, and lactose intolerance. I recommend you make an appointment with your primary care doctor so he or she can help you with your actual diagnosis and treatment."

• A patient of yours asks you a clinical question in an open forum such as Facebook or Twitter.

Sample question: "Hi, Doc. The birth control pills you gave me aren’t helping. I’ve been on them for 2 months, and I’m still having all the symptoms I had originally – mood swings, spotting, difficulty sleeping, and my acne’s not better. I think I need a different pill. Can you prescribe me one?"

Sample response: "I’m sorry to hear that. I’m happy to discuss this with you, but let’s do so privately. Please use our secure office e-mail to contact me, or call me during office hours and we can talk about what’s happening and what to do next. Hope to hear from you soon."

• Someone asks for specific product recommendations.

Sample question: "My doctor wants me to buy the sunscreen he sells in his office. He says it’s better than drug store brands, but it’s expensive. Is he telling the truth?"

Sample response: "I can’t speak specifically to your doctor’s sunscreen. But in general, you should look for a sunscreen that is labeled "broad spectrum," which protects against both UVA and UVB rays and has an SPF of 30-50. Most often, price doesn’t correlate with effectiveness. So, just because a sunscreen is more expensive doesn’t necessarily mean it’s more effective."

• Someone criticizes his current doctor or medical provider.

Sample question: "I’ve been going to my dermatologist for 6 months now and my acne hasn’t gotten any better. He put me on antibiotics and topical creams, and I still have acne. He obviously doesn’t know what he’s doing. Can you tell me what to do?"

Sample reply: "I’m sorry to hear that. I know how frustrating it can be. Acne can be very difficult to treat and can take a long time. Be sure that you’re communicating with your doctor about your situation so he can help you. Also, remember that you can always request a second opinion."

• You want to blog about a patient’s condition. How do you do it without violating the patient’s privacy while ensuring that he cannot be identified? One option is to obtain the patient’s written consent. Another option is to create a composite: Use real facts with fictional patients. For example, your actual patient is a 30-year-old UPS driver with severe hand eczema. You want to write about connections between hand eczema and occupational exposure. You create a fictional patient who is a 40-year-old female mail carrier. You discuss the symptoms of your actual patient in a way that maintains his privacy yet allows you to educate patients online.

Clearly, there are many more scenarios you may encounter online. This is a small sampling to give you some idea of how to respond safely and professionally. If you have specific questions or suggestions, feel free to share them by writing to [email protected].

Dr. Benabio is physician director of innovation at Kaiser Permanente in San Diego. Visit his consumer health blog at thedermblog.com and his health care blog at benabio.com. Connect with him on Twitter @Dermdoc and on Facebook (DermDoc).

We live in an increasingly social and connected world. As such, doctor-patient online communication will become more common. As I noted in my last column, many physicians see online communication as a minefield of potential patient privacy violations, and they are reluctant to use it. Rather than avoid it for fear of committing a privacy violation, I hope all physicians will educate themselves on how to communicate online safely and effectively. To this end, I’m providing some examples of online questions you will likely encounter, with sample responses.

• A nonpatient asks you to make a diagnosis online. As a dermatologist who is active in social media, I often have nonpatients send me photos of their skin conditions requesting a diagnosis.

Sample question: "I’ve attached a photo of a mole on my leg. Does it look OK to you, Doc? Could it be cancerous?"

Sample response: "Thank you for sending me the picture. Without an established doctor-patient relationship, I’m unable to provide a diagnosis. I recommend you make an appointment with your dermatologist. If you don’t have one, here’s a link to the American Academy of Dermatology website where you can enter your ZIP code to find a dermatologist near you."

• A nonpatient asks your opinion about symptoms he is experiencing.

Sample question: "I’ve been experiencing bouts of diarrhea and stomach cramping and think I have celiac disease. I’m going to stop eating gluten. Do you think that’s a good idea?"

Sample response: "I’m sorry you’ve been unwell. Unfortunately, I cannot provide medical advice to you since we don’t have an established doctor-patient relationship. I can tell you, however, that diarrhea and cramping can be symptomatic of many conditions including, but not limited to celiac disease, irritable bowel syndrome, and lactose intolerance. I recommend you make an appointment with your primary care doctor so he or she can help you with your actual diagnosis and treatment."

• A patient of yours asks you a clinical question in an open forum such as Facebook or Twitter.

Sample question: "Hi, Doc. The birth control pills you gave me aren’t helping. I’ve been on them for 2 months, and I’m still having all the symptoms I had originally – mood swings, spotting, difficulty sleeping, and my acne’s not better. I think I need a different pill. Can you prescribe me one?"

Sample response: "I’m sorry to hear that. I’m happy to discuss this with you, but let’s do so privately. Please use our secure office e-mail to contact me, or call me during office hours and we can talk about what’s happening and what to do next. Hope to hear from you soon."

• Someone asks for specific product recommendations.

Sample question: "My doctor wants me to buy the sunscreen he sells in his office. He says it’s better than drug store brands, but it’s expensive. Is he telling the truth?"

Sample response: "I can’t speak specifically to your doctor’s sunscreen. But in general, you should look for a sunscreen that is labeled "broad spectrum," which protects against both UVA and UVB rays and has an SPF of 30-50. Most often, price doesn’t correlate with effectiveness. So, just because a sunscreen is more expensive doesn’t necessarily mean it’s more effective."

• Someone criticizes his current doctor or medical provider.

Sample question: "I’ve been going to my dermatologist for 6 months now and my acne hasn’t gotten any better. He put me on antibiotics and topical creams, and I still have acne. He obviously doesn’t know what he’s doing. Can you tell me what to do?"

Sample reply: "I’m sorry to hear that. I know how frustrating it can be. Acne can be very difficult to treat and can take a long time. Be sure that you’re communicating with your doctor about your situation so he can help you. Also, remember that you can always request a second opinion."

• You want to blog about a patient’s condition. How do you do it without violating the patient’s privacy while ensuring that he cannot be identified? One option is to obtain the patient’s written consent. Another option is to create a composite: Use real facts with fictional patients. For example, your actual patient is a 30-year-old UPS driver with severe hand eczema. You want to write about connections between hand eczema and occupational exposure. You create a fictional patient who is a 40-year-old female mail carrier. You discuss the symptoms of your actual patient in a way that maintains his privacy yet allows you to educate patients online.

Clearly, there are many more scenarios you may encounter online. This is a small sampling to give you some idea of how to respond safely and professionally. If you have specific questions or suggestions, feel free to share them by writing to [email protected].

Dr. Benabio is physician director of innovation at Kaiser Permanente in San Diego. Visit his consumer health blog at thedermblog.com and his health care blog at benabio.com. Connect with him on Twitter @Dermdoc and on Facebook (DermDoc).

We live in an increasingly social and connected world. As such, doctor-patient online communication will become more common. As I noted in my last column, many physicians see online communication as a minefield of potential patient privacy violations, and they are reluctant to use it. Rather than avoid it for fear of committing a privacy violation, I hope all physicians will educate themselves on how to communicate online safely and effectively. To this end, I’m providing some examples of online questions you will likely encounter, with sample responses.

• A nonpatient asks you to make a diagnosis online. As a dermatologist who is active in social media, I often have nonpatients send me photos of their skin conditions requesting a diagnosis.

Sample question: "I’ve attached a photo of a mole on my leg. Does it look OK to you, Doc? Could it be cancerous?"

Sample response: "Thank you for sending me the picture. Without an established doctor-patient relationship, I’m unable to provide a diagnosis. I recommend you make an appointment with your dermatologist. If you don’t have one, here’s a link to the American Academy of Dermatology website where you can enter your ZIP code to find a dermatologist near you."

• A nonpatient asks your opinion about symptoms he is experiencing.

Sample question: "I’ve been experiencing bouts of diarrhea and stomach cramping and think I have celiac disease. I’m going to stop eating gluten. Do you think that’s a good idea?"

Sample response: "I’m sorry you’ve been unwell. Unfortunately, I cannot provide medical advice to you since we don’t have an established doctor-patient relationship. I can tell you, however, that diarrhea and cramping can be symptomatic of many conditions including, but not limited to celiac disease, irritable bowel syndrome, and lactose intolerance. I recommend you make an appointment with your primary care doctor so he or she can help you with your actual diagnosis and treatment."

• A patient of yours asks you a clinical question in an open forum such as Facebook or Twitter.

Sample question: "Hi, Doc. The birth control pills you gave me aren’t helping. I’ve been on them for 2 months, and I’m still having all the symptoms I had originally – mood swings, spotting, difficulty sleeping, and my acne’s not better. I think I need a different pill. Can you prescribe me one?"

Sample response: "I’m sorry to hear that. I’m happy to discuss this with you, but let’s do so privately. Please use our secure office e-mail to contact me, or call me during office hours and we can talk about what’s happening and what to do next. Hope to hear from you soon."

• Someone asks for specific product recommendations.

Sample question: "My doctor wants me to buy the sunscreen he sells in his office. He says it’s better than drug store brands, but it’s expensive. Is he telling the truth?"

Sample response: "I can’t speak specifically to your doctor’s sunscreen. But in general, you should look for a sunscreen that is labeled "broad spectrum," which protects against both UVA and UVB rays and has an SPF of 30-50. Most often, price doesn’t correlate with effectiveness. So, just because a sunscreen is more expensive doesn’t necessarily mean it’s more effective."

• Someone criticizes his current doctor or medical provider.

Sample question: "I’ve been going to my dermatologist for 6 months now and my acne hasn’t gotten any better. He put me on antibiotics and topical creams, and I still have acne. He obviously doesn’t know what he’s doing. Can you tell me what to do?"

Sample reply: "I’m sorry to hear that. I know how frustrating it can be. Acne can be very difficult to treat and can take a long time. Be sure that you’re communicating with your doctor about your situation so he can help you. Also, remember that you can always request a second opinion."

• You want to blog about a patient’s condition. How do you do it without violating the patient’s privacy while ensuring that he cannot be identified? One option is to obtain the patient’s written consent. Another option is to create a composite: Use real facts with fictional patients. For example, your actual patient is a 30-year-old UPS driver with severe hand eczema. You want to write about connections between hand eczema and occupational exposure. You create a fictional patient who is a 40-year-old female mail carrier. You discuss the symptoms of your actual patient in a way that maintains his privacy yet allows you to educate patients online.

Clearly, there are many more scenarios you may encounter online. This is a small sampling to give you some idea of how to respond safely and professionally. If you have specific questions or suggestions, feel free to share them by writing to [email protected].

Dr. Benabio is physician director of innovation at Kaiser Permanente in San Diego. Visit his consumer health blog at thedermblog.com and his health care blog at benabio.com. Connect with him on Twitter @Dermdoc and on Facebook (DermDoc).

Tough economic times and the unpredictable consequences of health care reform are making a growing number of solo practitioners and small private groups very nervous. I’ve been receiving many inquiries about protective options, such as joining a multispecialty group, or merging two or more small practices into larger entities.

If becoming an employee of a large corporation does not appeal to you, a merger can offer significant advantages in stabilization of income and expenses; but careful planning – and a written agreement – is essential.

If you are considering this option, here are some things to think about.

• What is the compensation formula? Will everyone be paid only for what they do individually, or will revenue be shared equally? I favor a combination, so productivity is rewarded but your income doesn’t drop to zero when you take time off.

• Who will be in charge, and what percentage vote will be needed to approve important decisions? Typically, the majority rules; but you may wish to create a list of pivotal moves that will require unanimous approval, such as purchasing expensive equipment, borrowing money, or adding new partners.

• Will you keep your retirement plans separate, or combine them? If the latter, you will have to agree on the terms of the new plan, which can be the same as or different from any of the existing plans. You’ll probably need some legal guidance to ensure that assets from existing plans can be transferred into a new plan without tax issues.

If both practices are incorporated, there are two basic options for combining them. Corporation A can simply absorb corporation B; the latter ceases to exist, and corporation A, the so-called "surviving entity," assumes all assets and liabilities of both old corporations. Corporation B shareholders exchange shares of its stock for shares of corporation A, with adjustments for any inequalities in stock value.

The second option is to start a completely new corporation, which I’ll call corporation C. Corporations A and B dissolve, and distribute their equipment and charts to their shareholders, who then transfer the assets to corporation C.

Option 2 is popular, but I am not a fan. It is billed as an opportunity to start fresh, shielding everyone from exposure to malpractice suits and other liabilities, but the reality is, anyone looking to sue either old corporation will simply sue corporation C as the so-called "successor" corporation, on the grounds that it has assumed responsibility for its predecessors’ liabilities. You also will need new provider numbers, which may impede cash flow for months. Plus, the IRS treats corporate liquidations, even for merger purposes, as sales of assets, and taxes them.

In general, most experts that I’ve talked with favor the outright merger of corporations; it is tax neutral, and while it may theoretically be less satisfactory liability-wise, you can minimize risk by examining financial and legal records, and by identifying any glaring flaws in charting or coding. Your lawyers can add "hold harmless" clauses to the merger agreement, indemnifying each party against the others’ liabilities. This area, especially, is where you need experienced, competent legal advice.

Another common sticking point is known as "equalization." Ideally, each party brings an equal amount of assets to the table, but in the real world that is hardly ever the case. One party may contribute more equipment, for example, and the others are often asked to make up the difference ("equalize") with something else, usually cash.

An alternative is to agree that any inequalities will be compensated at the other end, in the form of buyout value; that is, physicians contributing more assets will receive larger buyouts when they leave or retire than those contributing less.

Non-compete provisions are always a difficult issue, mostly because they are so hard (and expensive) to enforce. An increasingly popular alternative is, once again, to deal with it at the other end, with a buyout penalty. An unhappy partner can leave, and compete, but at the cost of a substantially reduced buyout. This permits competition, but discourages it; and it compensates the remaining partners.

These are only some of the pivotal business and legal issues that must be settled in advance. A little planning and negotiation can prevent a lot of grief, regret, and legal expenses in the future.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J.

Tough economic times and the unpredictable consequences of health care reform are making a growing number of solo practitioners and small private groups very nervous. I’ve been receiving many inquiries about protective options, such as joining a multispecialty group, or merging two or more small practices into larger entities.

If becoming an employee of a large corporation does not appeal to you, a merger can offer significant advantages in stabilization of income and expenses; but careful planning – and a written agreement – is essential.

If you are considering this option, here are some things to think about.

• What is the compensation formula? Will everyone be paid only for what they do individually, or will revenue be shared equally? I favor a combination, so productivity is rewarded but your income doesn’t drop to zero when you take time off.

• Who will be in charge, and what percentage vote will be needed to approve important decisions? Typically, the majority rules; but you may wish to create a list of pivotal moves that will require unanimous approval, such as purchasing expensive equipment, borrowing money, or adding new partners.

• Will you keep your retirement plans separate, or combine them? If the latter, you will have to agree on the terms of the new plan, which can be the same as or different from any of the existing plans. You’ll probably need some legal guidance to ensure that assets from existing plans can be transferred into a new plan without tax issues.

If both practices are incorporated, there are two basic options for combining them. Corporation A can simply absorb corporation B; the latter ceases to exist, and corporation A, the so-called "surviving entity," assumes all assets and liabilities of both old corporations. Corporation B shareholders exchange shares of its stock for shares of corporation A, with adjustments for any inequalities in stock value.

The second option is to start a completely new corporation, which I’ll call corporation C. Corporations A and B dissolve, and distribute their equipment and charts to their shareholders, who then transfer the assets to corporation C.

Option 2 is popular, but I am not a fan. It is billed as an opportunity to start fresh, shielding everyone from exposure to malpractice suits and other liabilities, but the reality is, anyone looking to sue either old corporation will simply sue corporation C as the so-called "successor" corporation, on the grounds that it has assumed responsibility for its predecessors’ liabilities. You also will need new provider numbers, which may impede cash flow for months. Plus, the IRS treats corporate liquidations, even for merger purposes, as sales of assets, and taxes them.

In general, most experts that I’ve talked with favor the outright merger of corporations; it is tax neutral, and while it may theoretically be less satisfactory liability-wise, you can minimize risk by examining financial and legal records, and by identifying any glaring flaws in charting or coding. Your lawyers can add "hold harmless" clauses to the merger agreement, indemnifying each party against the others’ liabilities. This area, especially, is where you need experienced, competent legal advice.

Another common sticking point is known as "equalization." Ideally, each party brings an equal amount of assets to the table, but in the real world that is hardly ever the case. One party may contribute more equipment, for example, and the others are often asked to make up the difference ("equalize") with something else, usually cash.

An alternative is to agree that any inequalities will be compensated at the other end, in the form of buyout value; that is, physicians contributing more assets will receive larger buyouts when they leave or retire than those contributing less.

Non-compete provisions are always a difficult issue, mostly because they are so hard (and expensive) to enforce. An increasingly popular alternative is, once again, to deal with it at the other end, with a buyout penalty. An unhappy partner can leave, and compete, but at the cost of a substantially reduced buyout. This permits competition, but discourages it; and it compensates the remaining partners.

These are only some of the pivotal business and legal issues that must be settled in advance. A little planning and negotiation can prevent a lot of grief, regret, and legal expenses in the future.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J.

Tough economic times and the unpredictable consequences of health care reform are making a growing number of solo practitioners and small private groups very nervous. I’ve been receiving many inquiries about protective options, such as joining a multispecialty group, or merging two or more small practices into larger entities.

If becoming an employee of a large corporation does not appeal to you, a merger can offer significant advantages in stabilization of income and expenses; but careful planning – and a written agreement – is essential.

If you are considering this option, here are some things to think about.

• What is the compensation formula? Will everyone be paid only for what they do individually, or will revenue be shared equally? I favor a combination, so productivity is rewarded but your income doesn’t drop to zero when you take time off.

• Who will be in charge, and what percentage vote will be needed to approve important decisions? Typically, the majority rules; but you may wish to create a list of pivotal moves that will require unanimous approval, such as purchasing expensive equipment, borrowing money, or adding new partners.

• Will you keep your retirement plans separate, or combine them? If the latter, you will have to agree on the terms of the new plan, which can be the same as or different from any of the existing plans. You’ll probably need some legal guidance to ensure that assets from existing plans can be transferred into a new plan without tax issues.

If both practices are incorporated, there are two basic options for combining them. Corporation A can simply absorb corporation B; the latter ceases to exist, and corporation A, the so-called "surviving entity," assumes all assets and liabilities of both old corporations. Corporation B shareholders exchange shares of its stock for shares of corporation A, with adjustments for any inequalities in stock value.

The second option is to start a completely new corporation, which I’ll call corporation C. Corporations A and B dissolve, and distribute their equipment and charts to their shareholders, who then transfer the assets to corporation C.

Option 2 is popular, but I am not a fan. It is billed as an opportunity to start fresh, shielding everyone from exposure to malpractice suits and other liabilities, but the reality is, anyone looking to sue either old corporation will simply sue corporation C as the so-called "successor" corporation, on the grounds that it has assumed responsibility for its predecessors’ liabilities. You also will need new provider numbers, which may impede cash flow for months. Plus, the IRS treats corporate liquidations, even for merger purposes, as sales of assets, and taxes them.

In general, most experts that I’ve talked with favor the outright merger of corporations; it is tax neutral, and while it may theoretically be less satisfactory liability-wise, you can minimize risk by examining financial and legal records, and by identifying any glaring flaws in charting or coding. Your lawyers can add "hold harmless" clauses to the merger agreement, indemnifying each party against the others’ liabilities. This area, especially, is where you need experienced, competent legal advice.

Another common sticking point is known as "equalization." Ideally, each party brings an equal amount of assets to the table, but in the real world that is hardly ever the case. One party may contribute more equipment, for example, and the others are often asked to make up the difference ("equalize") with something else, usually cash.

An alternative is to agree that any inequalities will be compensated at the other end, in the form of buyout value; that is, physicians contributing more assets will receive larger buyouts when they leave or retire than those contributing less.

Non-compete provisions are always a difficult issue, mostly because they are so hard (and expensive) to enforce. An increasingly popular alternative is, once again, to deal with it at the other end, with a buyout penalty. An unhappy partner can leave, and compete, but at the cost of a substantially reduced buyout. This permits competition, but discourages it; and it compensates the remaining partners.

These are only some of the pivotal business and legal issues that must be settled in advance. A little planning and negotiation can prevent a lot of grief, regret, and legal expenses in the future.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J.

The ATLAS trial¹
For decades, 5 years of tamoxifen has been the standard of care for the adjuvant therapy of women with estrogen receptor positive breast cancer, although in recent years for postmenopausal women this treatment has been largely replaced with aromatase inhibitors (AIs). Would extending tamoxifen therapy to 10 years provide further benefit or merely increase toxicity? Do the results of the ATLAS trial, in which nearly 13,000 women were recruited and randomized to receive 5 more years of tamoxifen or to stop tamoxifen at 5 years, provide us with a new standard of care for premenopausal women?

Click on the PDF icon at the top of this introduction to read the full article.

The ATLAS trial¹
For decades, 5 years of tamoxifen has been the standard of care for the adjuvant therapy of women with estrogen receptor positive breast cancer, although in recent years for postmenopausal women this treatment has been largely replaced with aromatase inhibitors (AIs). Would extending tamoxifen therapy to 10 years provide further benefit or merely increase toxicity? Do the results of the ATLAS trial, in which nearly 13,000 women were recruited and randomized to receive 5 more years of tamoxifen or to stop tamoxifen at 5 years, provide us with a new standard of care for premenopausal women?

Click on the PDF icon at the top of this introduction to read the full article.

The ATLAS trial¹
For decades, 5 years of tamoxifen has been the standard of care for the adjuvant therapy of women with estrogen receptor positive breast cancer, although in recent years for postmenopausal women this treatment has been largely replaced with aromatase inhibitors (AIs). Would extending tamoxifen therapy to 10 years provide further benefit or merely increase toxicity? Do the results of the ATLAS trial, in which nearly 13,000 women were recruited and randomized to receive 5 more years of tamoxifen or to stop tamoxifen at 5 years, provide us with a new standard of care for premenopausal women?

Click on the PDF icon at the top of this introduction to read the full article.

Rhabdomyosarcomas are a rare group of soft tissue neoplasms of mesenchymal origin. RMS is common among childhood cancers, but it is among the rarest of adult tumors. They account for about 5% of all childhood cancers.1 Soft-tissue sarcomas account for less than 1% of adult malignancies, and RMS account for only 3% of those sarcomas.2 Here, we report a case of RMS in the neck, which led to dysphagia due to external compression of the esophagus.

Click on the PDF icon at the top of this introduction to read the full article.

Rhabdomyosarcomas are a rare group of soft tissue neoplasms of mesenchymal origin. RMS is common among childhood cancers, but it is among the rarest of adult tumors. They account for about 5% of all childhood cancers.1 Soft-tissue sarcomas account for less than 1% of adult malignancies, and RMS account for only 3% of those sarcomas.2 Here, we report a case of RMS in the neck, which led to dysphagia due to external compression of the esophagus.

Click on the PDF icon at the top of this introduction to read the full article.

Rhabdomyosarcomas are a rare group of soft tissue neoplasms of mesenchymal origin. RMS is common among childhood cancers, but it is among the rarest of adult tumors. They account for about 5% of all childhood cancers.1 Soft-tissue sarcomas account for less than 1% of adult malignancies, and RMS account for only 3% of those sarcomas.2 Here, we report a case of RMS in the neck, which led to dysphagia due to external compression of the esophagus.

Click on the PDF icon at the top of this introduction to read the full article.

A recent report about medication management for hospitalized patients with psychiatric comorbidities shows that collaboration between hospitalists and specialists is key to improving the care of these patients.

The paper, "Challenges in Pharmacologic Management of the Hospitalized Patient with Psychiatric Comorbidity," suggests that "when making complex psychopharmacologic decisions," hospitalists should collaborate with pharmacists and psychiatrists. The study aims to help hospitalists make informed decisions when considering whether to continue home psychotropic medication in medically ill patients.

Martha Ward, MD, assistant professor in the department of psychiatry and behavioral sciences at Emory University School of Medicine in Atlanta and lead author of the study, says hospitalists are rightly focused on the acute problem in front of them, and they sometimes do not have time to address chronic, nonemergent issues, such as a psychiatric comorbidity.

"It's a mindset," Dr. Ward says. "At times when you're focused minute to minute on an emergent issue, it can be difficult to look at the chronic issues that don't come to the forefront."

Dr. Ward says it's important for hospitalists to never "reflexively discontinue" medications for patients with mental illness. Instead, she suggests weighing the risks and benefits of how existing medications would interact with new treatments.

Working with pharmacists, psychiatrists, or even tapping online resources that provide information about drug interactions is a good first step, she adds. Otherwise, physicians risk introducing complicating factors, such as potential adverse events related to psychiatric decompensation or psychotropic drug withdrawal.

Over the long term, Dr. Ward says, hospitalists should be educated in psychiatry, starting in medical school and in residency. "I'm somewhat biased," adds Dr. Ward, who is trained in both internal medicine and psychiatry. "I think internal-medicine doctors could benefit greatly from additional training. I think that's one of the biggest deficiencies in our curriculum."

Visit our website for more information about hospital medicine and psychiatry.

A recent report about medication management for hospitalized patients with psychiatric comorbidities shows that collaboration between hospitalists and specialists is key to improving the care of these patients.

The paper, "Challenges in Pharmacologic Management of the Hospitalized Patient with Psychiatric Comorbidity," suggests that "when making complex psychopharmacologic decisions," hospitalists should collaborate with pharmacists and psychiatrists. The study aims to help hospitalists make informed decisions when considering whether to continue home psychotropic medication in medically ill patients.

Martha Ward, MD, assistant professor in the department of psychiatry and behavioral sciences at Emory University School of Medicine in Atlanta and lead author of the study, says hospitalists are rightly focused on the acute problem in front of them, and they sometimes do not have time to address chronic, nonemergent issues, such as a psychiatric comorbidity.

"It's a mindset," Dr. Ward says. "At times when you're focused minute to minute on an emergent issue, it can be difficult to look at the chronic issues that don't come to the forefront."

Dr. Ward says it's important for hospitalists to never "reflexively discontinue" medications for patients with mental illness. Instead, she suggests weighing the risks and benefits of how existing medications would interact with new treatments.

Working with pharmacists, psychiatrists, or even tapping online resources that provide information about drug interactions is a good first step, she adds. Otherwise, physicians risk introducing complicating factors, such as potential adverse events related to psychiatric decompensation or psychotropic drug withdrawal.

Over the long term, Dr. Ward says, hospitalists should be educated in psychiatry, starting in medical school and in residency. "I'm somewhat biased," adds Dr. Ward, who is trained in both internal medicine and psychiatry. "I think internal-medicine doctors could benefit greatly from additional training. I think that's one of the biggest deficiencies in our curriculum."

Visit our website for more information about hospital medicine and psychiatry.

A recent report about medication management for hospitalized patients with psychiatric comorbidities shows that collaboration between hospitalists and specialists is key to improving the care of these patients.

The paper, "Challenges in Pharmacologic Management of the Hospitalized Patient with Psychiatric Comorbidity," suggests that "when making complex psychopharmacologic decisions," hospitalists should collaborate with pharmacists and psychiatrists. The study aims to help hospitalists make informed decisions when considering whether to continue home psychotropic medication in medically ill patients.

Martha Ward, MD, assistant professor in the department of psychiatry and behavioral sciences at Emory University School of Medicine in Atlanta and lead author of the study, says hospitalists are rightly focused on the acute problem in front of them, and they sometimes do not have time to address chronic, nonemergent issues, such as a psychiatric comorbidity.

"It's a mindset," Dr. Ward says. "At times when you're focused minute to minute on an emergent issue, it can be difficult to look at the chronic issues that don't come to the forefront."

Dr. Ward says it's important for hospitalists to never "reflexively discontinue" medications for patients with mental illness. Instead, she suggests weighing the risks and benefits of how existing medications would interact with new treatments.

Working with pharmacists, psychiatrists, or even tapping online resources that provide information about drug interactions is a good first step, she adds. Otherwise, physicians risk introducing complicating factors, such as potential adverse events related to psychiatric decompensation or psychotropic drug withdrawal.

Over the long term, Dr. Ward says, hospitalists should be educated in psychiatry, starting in medical school and in residency. "I'm somewhat biased," adds Dr. Ward, who is trained in both internal medicine and psychiatry. "I think internal-medicine doctors could benefit greatly from additional training. I think that's one of the biggest deficiencies in our curriculum."

Visit our website for more information about hospital medicine and psychiatry.

A hospital in Portland, Ore., has received a $560,000 grant from the TKF Foundation to design and build a therapeutic 6,800-square-foot, four-seasons garden onsite, then measure stress levels among patients, family, visitors, and staff members who go to it.

Legacy Emanuel Medical Center was awarded one of six National Open Spaces Sacred Places grants last June. The center is part of the six-hospital Legacy Health system, which serves the greater Portland region and Vancouver, Wash., and has a history of innovative green spaces connected with its hospital and hospice facilities, explains Teresia Hazen, MEd, HTR, QMHP, a registered horticultural therapist, Legacy’s director of therapeutic gardens, and the grant’s project manager.

The garden will be built in an open-air terrace between the hospital's family birth center and cardiovascular ICU. Grant funding will support incorporating such design elements as portals and pathways, public spaces, and areas where visitors can have some privacy, reflecting therapeutic garden characteristics defined by the American Horticultural Therapy Association, Hazen says. Researchers will then monitor the stress levels and heart rates of expectant mothers and their babies in utero, family members visiting ICU patients, and hospital staff members who spend time in the hospital garden.

Isadora Roth, MD, a hospitalist at two Legacy Health hospitals, appreciates the availability of hospital gardens for her patients and herself. "I often see patients out there, and they seem happier, more relaxed, and less anxious," Dr. Roth says. "I really think it has therapeutic benefits."

The new garden is scheduled to be completed in December; data will start to be gathered next April, Hazen says. Legacy also is planning a Therapeutic Landscapes Symposium on April 4, 2014, in Portland.

Visit our website for more information on stress and hospitalists.

A hospital in Portland, Ore., has received a $560,000 grant from the TKF Foundation to design and build a therapeutic 6,800-square-foot, four-seasons garden onsite, then measure stress levels among patients, family, visitors, and staff members who go to it.

Legacy Emanuel Medical Center was awarded one of six National Open Spaces Sacred Places grants last June. The center is part of the six-hospital Legacy Health system, which serves the greater Portland region and Vancouver, Wash., and has a history of innovative green spaces connected with its hospital and hospice facilities, explains Teresia Hazen, MEd, HTR, QMHP, a registered horticultural therapist, Legacy’s director of therapeutic gardens, and the grant’s project manager.

The garden will be built in an open-air terrace between the hospital's family birth center and cardiovascular ICU. Grant funding will support incorporating such design elements as portals and pathways, public spaces, and areas where visitors can have some privacy, reflecting therapeutic garden characteristics defined by the American Horticultural Therapy Association, Hazen says. Researchers will then monitor the stress levels and heart rates of expectant mothers and their babies in utero, family members visiting ICU patients, and hospital staff members who spend time in the hospital garden.

Isadora Roth, MD, a hospitalist at two Legacy Health hospitals, appreciates the availability of hospital gardens for her patients and herself. "I often see patients out there, and they seem happier, more relaxed, and less anxious," Dr. Roth says. "I really think it has therapeutic benefits."

The new garden is scheduled to be completed in December; data will start to be gathered next April, Hazen says. Legacy also is planning a Therapeutic Landscapes Symposium on April 4, 2014, in Portland.

Visit our website for more information on stress and hospitalists.

A hospital in Portland, Ore., has received a $560,000 grant from the TKF Foundation to design and build a therapeutic 6,800-square-foot, four-seasons garden onsite, then measure stress levels among patients, family, visitors, and staff members who go to it.

Legacy Emanuel Medical Center was awarded one of six National Open Spaces Sacred Places grants last June. The center is part of the six-hospital Legacy Health system, which serves the greater Portland region and Vancouver, Wash., and has a history of innovative green spaces connected with its hospital and hospice facilities, explains Teresia Hazen, MEd, HTR, QMHP, a registered horticultural therapist, Legacy’s director of therapeutic gardens, and the grant’s project manager.

The garden will be built in an open-air terrace between the hospital's family birth center and cardiovascular ICU. Grant funding will support incorporating such design elements as portals and pathways, public spaces, and areas where visitors can have some privacy, reflecting therapeutic garden characteristics defined by the American Horticultural Therapy Association, Hazen says. Researchers will then monitor the stress levels and heart rates of expectant mothers and their babies in utero, family members visiting ICU patients, and hospital staff members who spend time in the hospital garden.

Isadora Roth, MD, a hospitalist at two Legacy Health hospitals, appreciates the availability of hospital gardens for her patients and herself. "I often see patients out there, and they seem happier, more relaxed, and less anxious," Dr. Roth says. "I really think it has therapeutic benefits."

The new garden is scheduled to be completed in December; data will start to be gathered next April, Hazen says. Legacy also is planning a Therapeutic Landscapes Symposium on April 4, 2014, in Portland.

Visit our website for more information on stress and hospitalists.

Calophyllum inophyllum is a large, nondeciduous tree native to a wide swath of regions including Central and East Africa; a north-to-south swath of India; Southeast Asia; Polynesia; the Philippines; and Australia. A member of the mangosteen family (Clusiaceae, also known as Guttiferae), C. inophyllum is now cultivated in much of the tropical world.

The oil derived from this abundant plant is known by a wide variety of names, including Alexandrian laurel, beach mahogany, beauty leaf, beach calophyllum, dilo, and kamani. But perhaps it is best known by the French Polynesian name: tamanu. Tamanu oil has been used for hundreds of years in cuisine and to treat various medical conditions. Ocular burn and cutaneous wound healing are some distinct conditions for which the oil of C. inophyllum has a long history of use in traditional folk medicine (Oncol. Rep. 2012;28:1096-102; Int. J. Cosmet. Sci. 2002;24:341-8).

Wound healing and eye protection

The C. inophyllum components to which wound-healing activity have been attributed include calophyllolide and inophyllum, as well as various polyphenols, many of which exert antioxidant effects (Int. J. Cosmet. Sci. 2002;24:341-8).

Courtesy Wikimedia Commons/B.navez/Creative Commons License

Modern research buttresses the use of tamanu oil for corneal protection from burns. In 2007, Said et al. explored the anti-UV activity of tamanu oil for eye protection. They found that the botanical oil displayed a significant capacity to absorb UV radiation, even at low concentrations (1/10,000, v/v), with a sun protection factor ranging from 18 to 22. Concentrations of C. inophyllum oil of up to 1% were not cytotoxic to human conjunctival epithelial cells, with the agent acting against oxidative stress and DNA damage. In light of the apparent antioxidant and cytoprotective effects of C. inophyllum oil in the study, the researchers concluded that the oil has potential as a natural UV filter in ophthalmic formulations (Eur. J. Pharm. Sci. 2007;30:203-10).

In 2009, Said et al. performed in vitro, in vivo, and ex vivo studies to assess the effects of different rinsing and healing protocols for alkali-induced ocular burn and inflammation in rabbits. The researchers used NaOH to induce corneal reactions in the rabbits, followed by rinses with NaCl 0.9% or controlled-ionization marine formula combined with N-acetylcysteine or vegetable oils (from C. inophyllum and Aleurites moluccana). The investigators assessed corneal epithelium regeneration and inflammatory cell infiltration using in vivo confocal microscopy and ex vivo histological cuts. They found that the combination of controlled-ionization marine solution with 10% C. inophyllum oil and 90% A. moluccana oil promoted corneal epithelium regeneration while reducing inflammatory cells, suggesting its viability as ocular burn therapy (Ophthalmologica 2009;223:52-9).

Other medical benefits

A wide range of health benefits have been ascribed to tamanu oil, and the ingredient has been found in an increasing number of topical products. It is thought to impart anti-inflammatory, antioxidant, antibacterial, antiviral, and photoprotective activity.

In 2011, Ayyanar et al. concluded a 4-year study intended to ascertain the herbs used in traditional medicine practiced by the Kani tribes in the Tirunelveli hills of Western Ghats, India. The researchers identified 90 species of plants used traditionally as ethnomedicinal treatments, with 65 different indications reported, particularly dermatologic conditions and gastrointestinal illnesses. Based on their study, they identified 16 species, including C. inophyllum, for additional ethnopharmacological investigation as potential sources of new drug agents (J. Ethnopharmacol. 2011;134:851-64).

In 2004, Yimdjo et al. investigated the chemical constituents of the root bark and nut of C. inophyllum, resulting in the isolation of several compounds and the discovery of antibacterial activity against several microbes (Phytochemistry 2004;65:2789-95).

C. inophyllum leaf extracts from the islands of French Polynesia have also been touted for several constituents that hold promise as anti-HIV-1 agents, including inophyllum B and P (Anal. Chim. Acta 2008;624:147-53). In addition, quantitative high-performance liquid chromatography (HPLC) analysis of callus cultures of C. inophyllum has revealed the anti-HIV activity of the dipyranocoumarins inophyllum B and P (J. Biotechnol. 2007;130:346-53).

Tamanu oil also has demonstrated potential use for humans and domestic animals as an insect repellent, specifically against the stable fly, Stomoxys calcitrans (J. Med. Entomol. 2010;47:575-80; Pest Manag. Sci. 2010;66:1191-8).

In 2012, Tsai et al. investigated the anti-inflammatory properties of an acetone extract of C. inophyllum leaves using lipopolysaccharide (LPS)-induced RAW 264.7 cells to assess the impact of the extract on nitric oxide (NO) expression and inducible nitric oxide synthase (iNOS). They found that C. inophyllum significantly inhibited, in dose-dependent fashion, the LPS-induced synthesis of NO, in addition to the expression of iNOS, cyclooxygenase (COX)-2, and nuclear factor–kappa B (NF-kappaB). The researchers concluded that the C. inophyllum extract exhibits anti-inflammatory activity and has potential application to inflammatory conditions in human beings (Oncol. Rep. 2012;28:1096-102).

Cancer

Recent work suggests the anti-cancer potential of C. inophyllum. In a study just over a decade ago, Itogawa et al. examined the potential inhibitory effects of C. inophyllum 4-phenylcoumarin isolates on Epstein-Barr virus early antigen (EBV-EA) activation caused by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All 10 of the isolates displayed inhibitory activity against EBV and no cytotoxicity. The strongest compound tested was calocoumarin-A (5), which also demonstrated a significant capacity to suppress murine skin tumor promotion in a two-stage cancer model. The investigators concluded that some 4-phenylcoumarin constituents of C. inophyllum warrant further study as possible antitumor agents (Cancer Lett. 2001;169:15-19).

C. inophyllum was one of 155 extracts from 93 plant species found on peninsular Malaysia during a screening by Ong et al. in 2009 for in vitro photocytotoxic activity using human leukemia cells (cell line HL60). Further, C. inophyllum was among the 29 plants to lower the in vitro cell viability by more than 50% after exposure to 9.6 J/cm² of a broad-spectrum light when tested at a concentration of 20 mcg/mL (J. Photochem. Photobiol. B 2009;96:216-22). In addition, Li et al. isolated one new friedelane-type triterpene and seven previously discovered triterpenoids from the stems and leaves of C. inophyllum, and ascertained that they exhibited growth inhibitory activity against human leukemia HL-60 cells (Fitoterapia 2010;81:586-9).

In 2008, Xiao et al. isolated a new prenylated xanthone (caloxanthone) as well as two previously known xanthones from the ethanolic extract of C. inophyllum twigs and reported that two of the constituents (including the new xanthone) demonstrated cytotoxicity against myelogenous leukemia (cell line K562) (J. Asian Nat. Prod. Res. 2008;10:993-7).

C. inophyllum is known to contain an abundance of phytosterols – primarily stigmasterol and beta-sitosterol, which are steroids associated with several healthy benefits (stigmasterol is a potent antioxidant) – as well as delta-tocotrienol, a form of vitamin E that acts as an antioxidant and is associated with anticancer activity, particularly against murine melanoma (Phytochemistry 2005;66:1825-31; J. Nutr. 1997;127:668-74).

Conclusion

Tamanu oil certainly isn’t a passing fad for the numerous traditional societies in the mainly eastern and southern hemispheres who have used the botanical for medicinal and culinary purposes for centuries. As an ingredient in skin care products, though, more research is needed. While modern studies are promising, randomized, placebo-controlled clinical trials are necessary to establish a potential role of C. inophyllum in the large array of topical dermatologic formulations.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever. To respond to this column, or to suggest topics for future columns, write to her at [email protected].

Calophyllum inophyllum is a large, nondeciduous tree native to a wide swath of regions including Central and East Africa; a north-to-south swath of India; Southeast Asia; Polynesia; the Philippines; and Australia. A member of the mangosteen family (Clusiaceae, also known as Guttiferae), C. inophyllum is now cultivated in much of the tropical world.

The oil derived from this abundant plant is known by a wide variety of names, including Alexandrian laurel, beach mahogany, beauty leaf, beach calophyllum, dilo, and kamani. But perhaps it is best known by the French Polynesian name: tamanu. Tamanu oil has been used for hundreds of years in cuisine and to treat various medical conditions. Ocular burn and cutaneous wound healing are some distinct conditions for which the oil of C. inophyllum has a long history of use in traditional folk medicine (Oncol. Rep. 2012;28:1096-102; Int. J. Cosmet. Sci. 2002;24:341-8).

Wound healing and eye protection

The C. inophyllum components to which wound-healing activity have been attributed include calophyllolide and inophyllum, as well as various polyphenols, many of which exert antioxidant effects (Int. J. Cosmet. Sci. 2002;24:341-8).

Courtesy Wikimedia Commons/B.navez/Creative Commons License

Modern research buttresses the use of tamanu oil for corneal protection from burns. In 2007, Said et al. explored the anti-UV activity of tamanu oil for eye protection. They found that the botanical oil displayed a significant capacity to absorb UV radiation, even at low concentrations (1/10,000, v/v), with a sun protection factor ranging from 18 to 22. Concentrations of C. inophyllum oil of up to 1% were not cytotoxic to human conjunctival epithelial cells, with the agent acting against oxidative stress and DNA damage. In light of the apparent antioxidant and cytoprotective effects of C. inophyllum oil in the study, the researchers concluded that the oil has potential as a natural UV filter in ophthalmic formulations (Eur. J. Pharm. Sci. 2007;30:203-10).

In 2009, Said et al. performed in vitro, in vivo, and ex vivo studies to assess the effects of different rinsing and healing protocols for alkali-induced ocular burn and inflammation in rabbits. The researchers used NaOH to induce corneal reactions in the rabbits, followed by rinses with NaCl 0.9% or controlled-ionization marine formula combined with N-acetylcysteine or vegetable oils (from C. inophyllum and Aleurites moluccana). The investigators assessed corneal epithelium regeneration and inflammatory cell infiltration using in vivo confocal microscopy and ex vivo histological cuts. They found that the combination of controlled-ionization marine solution with 10% C. inophyllum oil and 90% A. moluccana oil promoted corneal epithelium regeneration while reducing inflammatory cells, suggesting its viability as ocular burn therapy (Ophthalmologica 2009;223:52-9).

Other medical benefits

A wide range of health benefits have been ascribed to tamanu oil, and the ingredient has been found in an increasing number of topical products. It is thought to impart anti-inflammatory, antioxidant, antibacterial, antiviral, and photoprotective activity.

In 2011, Ayyanar et al. concluded a 4-year study intended to ascertain the herbs used in traditional medicine practiced by the Kani tribes in the Tirunelveli hills of Western Ghats, India. The researchers identified 90 species of plants used traditionally as ethnomedicinal treatments, with 65 different indications reported, particularly dermatologic conditions and gastrointestinal illnesses. Based on their study, they identified 16 species, including C. inophyllum, for additional ethnopharmacological investigation as potential sources of new drug agents (J. Ethnopharmacol. 2011;134:851-64).

In 2004, Yimdjo et al. investigated the chemical constituents of the root bark and nut of C. inophyllum, resulting in the isolation of several compounds and the discovery of antibacterial activity against several microbes (Phytochemistry 2004;65:2789-95).

C. inophyllum leaf extracts from the islands of French Polynesia have also been touted for several constituents that hold promise as anti-HIV-1 agents, including inophyllum B and P (Anal. Chim. Acta 2008;624:147-53). In addition, quantitative high-performance liquid chromatography (HPLC) analysis of callus cultures of C. inophyllum has revealed the anti-HIV activity of the dipyranocoumarins inophyllum B and P (J. Biotechnol. 2007;130:346-53).

Tamanu oil also has demonstrated potential use for humans and domestic animals as an insect repellent, specifically against the stable fly, Stomoxys calcitrans (J. Med. Entomol. 2010;47:575-80; Pest Manag. Sci. 2010;66:1191-8).

In 2012, Tsai et al. investigated the anti-inflammatory properties of an acetone extract of C. inophyllum leaves using lipopolysaccharide (LPS)-induced RAW 264.7 cells to assess the impact of the extract on nitric oxide (NO) expression and inducible nitric oxide synthase (iNOS). They found that C. inophyllum significantly inhibited, in dose-dependent fashion, the LPS-induced synthesis of NO, in addition to the expression of iNOS, cyclooxygenase (COX)-2, and nuclear factor–kappa B (NF-kappaB). The researchers concluded that the C. inophyllum extract exhibits anti-inflammatory activity and has potential application to inflammatory conditions in human beings (Oncol. Rep. 2012;28:1096-102).

Cancer

Recent work suggests the anti-cancer potential of C. inophyllum. In a study just over a decade ago, Itogawa et al. examined the potential inhibitory effects of C. inophyllum 4-phenylcoumarin isolates on Epstein-Barr virus early antigen (EBV-EA) activation caused by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All 10 of the isolates displayed inhibitory activity against EBV and no cytotoxicity. The strongest compound tested was calocoumarin-A (5), which also demonstrated a significant capacity to suppress murine skin tumor promotion in a two-stage cancer model. The investigators concluded that some 4-phenylcoumarin constituents of C. inophyllum warrant further study as possible antitumor agents (Cancer Lett. 2001;169:15-19).

C. inophyllum was one of 155 extracts from 93 plant species found on peninsular Malaysia during a screening by Ong et al. in 2009 for in vitro photocytotoxic activity using human leukemia cells (cell line HL60). Further, C. inophyllum was among the 29 plants to lower the in vitro cell viability by more than 50% after exposure to 9.6 J/cm² of a broad-spectrum light when tested at a concentration of 20 mcg/mL (J. Photochem. Photobiol. B 2009;96:216-22). In addition, Li et al. isolated one new friedelane-type triterpene and seven previously discovered triterpenoids from the stems and leaves of C. inophyllum, and ascertained that they exhibited growth inhibitory activity against human leukemia HL-60 cells (Fitoterapia 2010;81:586-9).

In 2008, Xiao et al. isolated a new prenylated xanthone (caloxanthone) as well as two previously known xanthones from the ethanolic extract of C. inophyllum twigs and reported that two of the constituents (including the new xanthone) demonstrated cytotoxicity against myelogenous leukemia (cell line K562) (J. Asian Nat. Prod. Res. 2008;10:993-7).

C. inophyllum is known to contain an abundance of phytosterols – primarily stigmasterol and beta-sitosterol, which are steroids associated with several healthy benefits (stigmasterol is a potent antioxidant) – as well as delta-tocotrienol, a form of vitamin E that acts as an antioxidant and is associated with anticancer activity, particularly against murine melanoma (Phytochemistry 2005;66:1825-31; J. Nutr. 1997;127:668-74).

Conclusion

Tamanu oil certainly isn’t a passing fad for the numerous traditional societies in the mainly eastern and southern hemispheres who have used the botanical for medicinal and culinary purposes for centuries. As an ingredient in skin care products, though, more research is needed. While modern studies are promising, randomized, placebo-controlled clinical trials are necessary to establish a potential role of C. inophyllum in the large array of topical dermatologic formulations.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever. To respond to this column, or to suggest topics for future columns, write to her at [email protected].

Calophyllum inophyllum is a large, nondeciduous tree native to a wide swath of regions including Central and East Africa; a north-to-south swath of India; Southeast Asia; Polynesia; the Philippines; and Australia. A member of the mangosteen family (Clusiaceae, also known as Guttiferae), C. inophyllum is now cultivated in much of the tropical world.

The oil derived from this abundant plant is known by a wide variety of names, including Alexandrian laurel, beach mahogany, beauty leaf, beach calophyllum, dilo, and kamani. But perhaps it is best known by the French Polynesian name: tamanu. Tamanu oil has been used for hundreds of years in cuisine and to treat various medical conditions. Ocular burn and cutaneous wound healing are some distinct conditions for which the oil of C. inophyllum has a long history of use in traditional folk medicine (Oncol. Rep. 2012;28:1096-102; Int. J. Cosmet. Sci. 2002;24:341-8).

Wound healing and eye protection

The C. inophyllum components to which wound-healing activity have been attributed include calophyllolide and inophyllum, as well as various polyphenols, many of which exert antioxidant effects (Int. J. Cosmet. Sci. 2002;24:341-8).

Courtesy Wikimedia Commons/B.navez/Creative Commons License

Modern research buttresses the use of tamanu oil for corneal protection from burns. In 2007, Said et al. explored the anti-UV activity of tamanu oil for eye protection. They found that the botanical oil displayed a significant capacity to absorb UV radiation, even at low concentrations (1/10,000, v/v), with a sun protection factor ranging from 18 to 22. Concentrations of C. inophyllum oil of up to 1% were not cytotoxic to human conjunctival epithelial cells, with the agent acting against oxidative stress and DNA damage. In light of the apparent antioxidant and cytoprotective effects of C. inophyllum oil in the study, the researchers concluded that the oil has potential as a natural UV filter in ophthalmic formulations (Eur. J. Pharm. Sci. 2007;30:203-10).

In 2009, Said et al. performed in vitro, in vivo, and ex vivo studies to assess the effects of different rinsing and healing protocols for alkali-induced ocular burn and inflammation in rabbits. The researchers used NaOH to induce corneal reactions in the rabbits, followed by rinses with NaCl 0.9% or controlled-ionization marine formula combined with N-acetylcysteine or vegetable oils (from C. inophyllum and Aleurites moluccana). The investigators assessed corneal epithelium regeneration and inflammatory cell infiltration using in vivo confocal microscopy and ex vivo histological cuts. They found that the combination of controlled-ionization marine solution with 10% C. inophyllum oil and 90% A. moluccana oil promoted corneal epithelium regeneration while reducing inflammatory cells, suggesting its viability as ocular burn therapy (Ophthalmologica 2009;223:52-9).

Other medical benefits

A wide range of health benefits have been ascribed to tamanu oil, and the ingredient has been found in an increasing number of topical products. It is thought to impart anti-inflammatory, antioxidant, antibacterial, antiviral, and photoprotective activity.

In 2011, Ayyanar et al. concluded a 4-year study intended to ascertain the herbs used in traditional medicine practiced by the Kani tribes in the Tirunelveli hills of Western Ghats, India. The researchers identified 90 species of plants used traditionally as ethnomedicinal treatments, with 65 different indications reported, particularly dermatologic conditions and gastrointestinal illnesses. Based on their study, they identified 16 species, including C. inophyllum, for additional ethnopharmacological investigation as potential sources of new drug agents (J. Ethnopharmacol. 2011;134:851-64).

In 2004, Yimdjo et al. investigated the chemical constituents of the root bark and nut of C. inophyllum, resulting in the isolation of several compounds and the discovery of antibacterial activity against several microbes (Phytochemistry 2004;65:2789-95).

C. inophyllum leaf extracts from the islands of French Polynesia have also been touted for several constituents that hold promise as anti-HIV-1 agents, including inophyllum B and P (Anal. Chim. Acta 2008;624:147-53). In addition, quantitative high-performance liquid chromatography (HPLC) analysis of callus cultures of C. inophyllum has revealed the anti-HIV activity of the dipyranocoumarins inophyllum B and P (J. Biotechnol. 2007;130:346-53).

Tamanu oil also has demonstrated potential use for humans and domestic animals as an insect repellent, specifically against the stable fly, Stomoxys calcitrans (J. Med. Entomol. 2010;47:575-80; Pest Manag. Sci. 2010;66:1191-8).

In 2012, Tsai et al. investigated the anti-inflammatory properties of an acetone extract of C. inophyllum leaves using lipopolysaccharide (LPS)-induced RAW 264.7 cells to assess the impact of the extract on nitric oxide (NO) expression and inducible nitric oxide synthase (iNOS). They found that C. inophyllum significantly inhibited, in dose-dependent fashion, the LPS-induced synthesis of NO, in addition to the expression of iNOS, cyclooxygenase (COX)-2, and nuclear factor–kappa B (NF-kappaB). The researchers concluded that the C. inophyllum extract exhibits anti-inflammatory activity and has potential application to inflammatory conditions in human beings (Oncol. Rep. 2012;28:1096-102).

Cancer

Recent work suggests the anti-cancer potential of C. inophyllum. In a study just over a decade ago, Itogawa et al. examined the potential inhibitory effects of C. inophyllum 4-phenylcoumarin isolates on Epstein-Barr virus early antigen (EBV-EA) activation caused by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All 10 of the isolates displayed inhibitory activity against EBV and no cytotoxicity. The strongest compound tested was calocoumarin-A (5), which also demonstrated a significant capacity to suppress murine skin tumor promotion in a two-stage cancer model. The investigators concluded that some 4-phenylcoumarin constituents of C. inophyllum warrant further study as possible antitumor agents (Cancer Lett. 2001;169:15-19).

C. inophyllum was one of 155 extracts from 93 plant species found on peninsular Malaysia during a screening by Ong et al. in 2009 for in vitro photocytotoxic activity using human leukemia cells (cell line HL60). Further, C. inophyllum was among the 29 plants to lower the in vitro cell viability by more than 50% after exposure to 9.6 J/cm² of a broad-spectrum light when tested at a concentration of 20 mcg/mL (J. Photochem. Photobiol. B 2009;96:216-22). In addition, Li et al. isolated one new friedelane-type triterpene and seven previously discovered triterpenoids from the stems and leaves of C. inophyllum, and ascertained that they exhibited growth inhibitory activity against human leukemia HL-60 cells (Fitoterapia 2010;81:586-9).

In 2008, Xiao et al. isolated a new prenylated xanthone (caloxanthone) as well as two previously known xanthones from the ethanolic extract of C. inophyllum twigs and reported that two of the constituents (including the new xanthone) demonstrated cytotoxicity against myelogenous leukemia (cell line K562) (J. Asian Nat. Prod. Res. 2008;10:993-7).

C. inophyllum is known to contain an abundance of phytosterols – primarily stigmasterol and beta-sitosterol, which are steroids associated with several healthy benefits (stigmasterol is a potent antioxidant) – as well as delta-tocotrienol, a form of vitamin E that acts as an antioxidant and is associated with anticancer activity, particularly against murine melanoma (Phytochemistry 2005;66:1825-31; J. Nutr. 1997;127:668-74).

Conclusion

Tamanu oil certainly isn’t a passing fad for the numerous traditional societies in the mainly eastern and southern hemispheres who have used the botanical for medicinal and culinary purposes for centuries. As an ingredient in skin care products, though, more research is needed. While modern studies are promising, randomized, placebo-controlled clinical trials are necessary to establish a potential role of C. inophyllum in the large array of topical dermatologic formulations.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever. To respond to this column, or to suggest topics for future columns, write to her at [email protected].

Since President Richard Nixon declared war on cancer more than 40 years ago, there have been significant increases in the number of people who survive cancer. Alongside advances in screening, detection, and diagnosis, the development of targeted anticancer agents has been a major contributory factor to this success. We highlight some of the key developments that have shaped oncological practice in recent decades and those that will likely have a significant impact in the near future.

*Click on the link to the left for a PDF of the full article.  
 

Since President Richard Nixon declared war on cancer more than 40 years ago, there have been significant increases in the number of people who survive cancer. Alongside advances in screening, detection, and diagnosis, the development of targeted anticancer agents has been a major contributory factor to this success. We highlight some of the key developments that have shaped oncological practice in recent decades and those that will likely have a significant impact in the near future.

*Click on the link to the left for a PDF of the full article.  
 

Since President Richard Nixon declared war on cancer more than 40 years ago, there have been significant increases in the number of people who survive cancer. Alongside advances in screening, detection, and diagnosis, the development of targeted anticancer agents has been a major contributory factor to this success. We highlight some of the key developments that have shaped oncological practice in recent decades and those that will likely have a significant impact in the near future.

*Click on the link to the left for a PDF of the full article.  
 

Patients with gastrointestinal stromal tumors (GIST) used to have a poor prognosis due to the very low response rate of these tumors to conventional chemotherapy and radiation therapy. However, following the introduction of imatinib as a targeted therapeutic agent with efficacy in GIST, survival outcomes have improved remarkably for patients in the advanced/metastatic and adjuvant settings. Imatinib is now approved for both indications and has become the standard of care for patients with GIST. Despite the mounting evidence demonstrating the clinical benefits of extending imatinib treatment beyond 1 year, the optimal duration of imatinib therapy has not yet been determined. Similarly, whether chronic or extended adjuvant imatinib therapy can further improve clinical outcomes in patients with GIST remains to be determined. In this review, we present recent findings from various clinical trials which indicate that prolonged, uninterrupted imatinib treatment can have durable clinical benefits in patients who underwent resection of primary, operable GIST, as well as patients with advanced, unresectable, or metastatic GIST. We also summarize data showing that treatment interruption can result in disease progression in both the adjuvant and advanced/metastatic settings. Finally, we present evidence from different trials that long-term imatinib therapy is feasible and safe (ie, without cumulative toxicities) in patients with GIST.

*Click on the link to the left for a PDF of the full article.   

Patients with gastrointestinal stromal tumors (GIST) used to have a poor prognosis due to the very low response rate of these tumors to conventional chemotherapy and radiation therapy. However, following the introduction of imatinib as a targeted therapeutic agent with efficacy in GIST, survival outcomes have improved remarkably for patients in the advanced/metastatic and adjuvant settings. Imatinib is now approved for both indications and has become the standard of care for patients with GIST. Despite the mounting evidence demonstrating the clinical benefits of extending imatinib treatment beyond 1 year, the optimal duration of imatinib therapy has not yet been determined. Similarly, whether chronic or extended adjuvant imatinib therapy can further improve clinical outcomes in patients with GIST remains to be determined. In this review, we present recent findings from various clinical trials which indicate that prolonged, uninterrupted imatinib treatment can have durable clinical benefits in patients who underwent resection of primary, operable GIST, as well as patients with advanced, unresectable, or metastatic GIST. We also summarize data showing that treatment interruption can result in disease progression in both the adjuvant and advanced/metastatic settings. Finally, we present evidence from different trials that long-term imatinib therapy is feasible and safe (ie, without cumulative toxicities) in patients with GIST.

*Click on the link to the left for a PDF of the full article.   

Patients with gastrointestinal stromal tumors (GIST) used to have a poor prognosis due to the very low response rate of these tumors to conventional chemotherapy and radiation therapy. However, following the introduction of imatinib as a targeted therapeutic agent with efficacy in GIST, survival outcomes have improved remarkably for patients in the advanced/metastatic and adjuvant settings. Imatinib is now approved for both indications and has become the standard of care for patients with GIST. Despite the mounting evidence demonstrating the clinical benefits of extending imatinib treatment beyond 1 year, the optimal duration of imatinib therapy has not yet been determined. Similarly, whether chronic or extended adjuvant imatinib therapy can further improve clinical outcomes in patients with GIST remains to be determined. In this review, we present recent findings from various clinical trials which indicate that prolonged, uninterrupted imatinib treatment can have durable clinical benefits in patients who underwent resection of primary, operable GIST, as well as patients with advanced, unresectable, or metastatic GIST. We also summarize data showing that treatment interruption can result in disease progression in both the adjuvant and advanced/metastatic settings. Finally, we present evidence from different trials that long-term imatinib therapy is feasible and safe (ie, without cumulative toxicities) in patients with GIST.

*Click on the link to the left for a PDF of the full article.